Conditions: Prostate Adenocarcinoma
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 57
Healthy volunteers: no

Brief summary:
This pilot partially-randomized phase II trial studies how well Supportive Therapy in Androgen Deprivation (STAND) clinic works in improving health outcomes and managing side effects in patients with prostate cancer. Individualized counseling regarding exercise and dietary habits may help improve patient understanding, satisfaction, and overall lessen adverse impact on quality of life caused by androgen deprivation.

Detailed description:
PRIMARY OBJECTIVES:

I. To compare the mean percent change from baseline to 12 months in percentage body fat mass among men with prostate cancer receiving androgen deprivation therapy randomized to participate in the ?STAND? clinic versus (vs.) usual standard of care. (Randomized Cohort) II. To determine the feasibility of completing multi-disciplinary STAND clinic visits within context of concurrent chemohormonal therapy for prostate cancer. (Non-randomized Pilot Cohort)

SECONDARY OBJECTIVES:

I. To compare the mean percent change from baseline to 12 months and patterns of change over time during participation in the STAND clinic vs. usual standard of care with respect to: metabolic impact on diabetes and cardiovascular risk factors, bone health, and quality of life/psychosocial impact.

II. Among men randomized to receive usual standard of care that cross-over to participate in the STAND clinic after month 12 of the study: to measure the mean change from baseline at start of participation in the STAND clinic after 12 months of participation in: metabolic parameters including percentage body fat, fasting insulin/glucose, homeostatic model assessment insulin resistance (HOMA-IR), body weight/body mass index, waist circumference; bone health; quality of life; and patient satisfaction.

III. Among men in the non-randomized pilot cohort: to determine the mean change from baseline to 12 months during STAND clinic participation in the primary and secondary metabolic and quality of life parameters listed above.

TERTIARY OBJECTIVES:

I. To investigate for a relationship between inherited genetic polymorphisms of functional relevance near or within genes encoding proteins with roles in steroid hormone transport and androgen receptor signaling with changes in metabolic parameters among men treated with androgen deprivation therapy.

II. To investigate changes in trabecular bone micro-architecture as measured by high resolution peripheral quantitative computed tomography (QCT) Imaging of radius and tibia during androgen deprivation therapy.

III. To investigate for relationship between 2nd digit to 4th digit length ratio (2D:4D ratio) and quality of life on androgen deprivation therapy.

IV. To investigate for a relationship between 2nd digit to 4th digit length ratio and baseline empathy score as measured by validated questionnaire.

OUTLINE: Patients receiving androgen deprivation therapy are randomized to 1 of 2 arms and patients receiving concurrent chemohormonal therapy are assigned to Arm II.

ARM I (STANDARD OF CARE): Patients receive leuprolide acetate subcutaneously (SC) or intramuscularly (IM), goserelin acetate SC, or triptorelin pamoate IM and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

ARM II (STAND CLINIC): Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietician, and symptom management service to receive individualized counseling monthly for 12 months.

After completion of study treatment, patients are followed up at 2, 4, and 6 months.

Arms:
arm 1: Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months. arm 2: Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietician, and symptom management service to receive individualized counseling monthly for 12 months.

Interventions: intervention 1: Behavioral Dietary Intervention intervention 2: Counseling intervention 3: Educational Intervention intervention 4: Exercise Intervention intervention 5: Goserelin Acetate intervention 6: Laboratory Biomarker Analysis intervention 7: Leuprolide Acetate intervention 8: Quality-of-Life Assessment intervention 9: Triptorelin Pamoate
Intervention descriptions: intervention 1: Receive individualized nutrition counseling intervention 2: Receive individualized symptom management service counseling intervention 3: Review educational modules intervention 4: Receive individualized exercise counseling intervention 5: Given SC intervention 6: Correlative studies intervention 7: Given SC or IM intervention 8: Ancillary studies intervention 9: Given IM

Protocol document:
Prot_SAP_000.pdf: 
A   M ulti dis ci pli n a r y   T e a  m  -B as e d   A p p r o a c h t o   Miti g at e t h e   I  m p a ct  of 
A n d r o g e n   D e p ri v ati o n   T h e r a p y   i n P r ost at e   C a n c e r:  a   R a n d o  mi z e d  P h as e  2 
T h e  “ S  T  A  N  D ” (  S u p p o rti v e  T  h e r a p y i n  A n d r o g e n  D  e p ri v ati o n)   Cli ni c  
P r ot o c ol  N u  m b e r   C  C #    1 3 5 5 1 3 
I  N  D #:   1 2 1 8 4 6 (  E x e  m pt) 
P ri n ci p al  I n v esti g at o r 
R a h ul   A g g a  r  w al M  D   
Di visi o n  of   H e  m at ol o g y/  O n c ol o g y,   D e p art  m e nt  of   M e di ci n e 
U ni v ersit y  of   C alif or ni a   S a n  Fr a n cis c o  
 
 
E  m ail:   R a h ul.  A g g ar  w al  @ u csf. e d u   
C o  -I n v esti g at o rs a n d   K e y  St u d y  P e rs o n n el : 
Eri c J .  S  m all, M  D   
T a  m  m y  J.   R o d v elt,   N P 
C h arl es   R y a n  , M  D   
M a c k   R o a c h III,   M  D,  F  A  C  R   
Al b ert   C h a n g,   M  D,  P h  D 
Al e x a n d er   G otts c h al k,   M  D,  P h  D 
Gr et a   M a c air e  , R  D   
G er o ni  m a   C ort es e  -Ji  m e n e z, R  N,   M P  H   
R e g a n  F e dri c,   E x er cis e  P h ysi ol o gist  
M a x  w ell   M e n g,   M  D   
J effr e y   B el k or a,  P h  D  
K  irst e n   Gr e e n e,   M  D,   M S  
P et er   C arr oll,   M  D,   M P  H  
M att h e  w   C o o p er b er g,   M  D,   M P  H 
Mi c h a el   R a b o  w,   M  D   
A  m y  Li n,   M  D 
L a  wr e n c e  F o n g,  M  D   
T er e n c e  Fri e dl a n d er,  M  D   
A n dr e  w   Hs  i e h, M  D   
W o n   Ki  m,   M  D   
D e a n n a   Kr o et z,   P h  D 
J u n e   C h a n, S c  D  
Eri n   Ri c h  m a n,  S c  D 
S h ar  mil a   M aj u  m d ar,  P h  D 
R a  mi   W ei n b er g,  P T   
St atisti ci a n:  
Li  Z h a n g,  P h  D,  U  C S F   Bi ost atisti cs   C or e   
R e visi o n   Hist o r y   
V ersi o n  1  d at e d  S e pt.  1 8,  2 0 1 3 
V ersi o n  2  d at e d  1 2- 2 6,  2 0 1 3   
V ersi o n  2. 1  d at e d  2- 1 2- 2 0 1 4   
V ersi o n  3. 0  d at e d  0 7- 0 7- 2 0 1 5
N C T # 0 2 1 6 8 0 6 2


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
P r ot o c ol  Si g n at u r e  P a g e  
Pr ot o c ol   N o.:   3. 0  
V er si o n   D at e:   0 7 -0 7 -2 0 1 5  
1.    I  a gr e e t o f oll o  w t hi s  pr ot o c ol  v er si o n  a s  a p pr o v e d  b y t h e   U  C  S F   Pr ot o c ol   R e vi e  w   C o  m  mitt e e 
(  P  R  C), C o  m  mitt e e  o n   H u  m a n   R e s e ar c h (  C  H  R),  a n d   D at a   S af et y   M o nit ori n g   C o  m  mitt e e   
(  D  S  M  C).  
2.    I   will  c o n d u ct t h e  st u d y i n  a c c or d a n c e   wit h  a p pli c a bl e   C  H  R r e q uir e  m e nt s,  F e d er al 
r e g ul ati o n s,  a n d  st at e  a n d l o c al l a  w s t o   m ai nt ai n t h e  pr ot e cti o n  of t h e ri g ht s  a n d   w elf ar e  of 
st u d y  p arti ci p a nt s.   
3.    I  c ertif y t h at I,  a n d t h e  st u d y  st aff,  h a v e r e c ei v e d t h e r e q ui sit e tr ai ni n g t o  c o n d u ct t hi s 
r e s e ar c h  pr ot o c ol.  
4.    I  h a v e r e a d  a n d  u n d er st a n d t h e i nf or  m ati o n i n t h e I n v e sti g at or s’   Br o c h ur e ( or   M a n uf a ct ur er’ s 
Br o c h ur e) r e g ar di n g t h e ri s k s   a n d  p ot e nti al  b e n efit s. I  a gr e e t o  c o n d u ct t h e  pr ot o c ol i n 
a c c or d a n c e   wit h   G o o d   Cli ni c al   Pr a cti c e s (I  C  H -G  C  P), t h e  a p pli c a bl e  et hi c al  pri n ci pl e s, t h e 
St at e  m e nt  of I n v e sti g at or ( F or  m  F  D  A  1 5 7 2),  a n d   wit h l o c al r e g ul at or y r e q uir e  m e nt s. I n 
a c c or d a n c e   wit h t h e  F  D A   M o d er ni z ati o n   A ct, I   will  e n s ur e t h e r e gi str ati o n  of t h e tri al  o n t h e 
w  w  w. cli ni c altri al s. g o v   w e b sit e.    
5.    I  a gr e e t o   m ai nt ai n  a d e q u at e  a n d  a c c ur at e r e c or d s i n  a c c or d a n c e   wit h   C  H  R  p oli ci e s, 
F e d er al,  st at e  a n d l o c al l a  w s  a n d r e g ul ati o n s.  
U  C  S F   Pri n ci p al I n v e s  ti g at or /   St u d y   C h air   
   
 
Pri nt e d   N a  m e   
   
 
Si g n at ur e   
   
D at e   
 
Pri n ci p al I n v e sti g at or   
   
Sit e   
Pri nt e d   N a  m e   
   
 
Si g n at ur e   
   
D at e   
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  2   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A B S T  R A C T  
 
Titl e   
A   M ulti dis ci pli n a r y   T e a  m  -B as e d   A p p r o a c h t o   Miti g at e t h e I  m p a ct  of   A n d r o g e n 
D e p ri v ati o n   T h e r a p y   i n  P r ost at e   C a n c e r: a   R a n d o  mi z e d  P h as e  2  St u d y  of t h e  “ S  T  A  N  D ” 
Cli ni c   
P ati e nt 
p o p ul ati o n 
8 0  p ati e nts   wit h  pr ost at e  c a n c er  w h o  h a v e   r e c e ntl y  st art e d  (  wit hi n  6    m o nt hs  of  st u d y  e ntr y) or 
pl a n t o  p urs u e  a n dr o g e n  d e pri v ati o n t h er a p y  (  A  D T),   wit h  a n  e x p e ct e d  d ur ati o n  of t h er a p y  of  at 
l e ast  1 2    m o nt hs  f oll o  wi n g  st u d y  e nr oll  m e nt,    will  b e  eli gi bl e  t o  p arti ci p at e  i n  t h e  r a n d o  mi z e d 
st u d y.  T  w e nt y  ( 2 0)  p ati e nts  c urr e ntl y  r e c ei vi n g  or  pl a n ni n g  t o  st art  c o  m bi n e d  c h e  m o h or  m o n al 
t h er a p y   will  b e  eli gi bl e t o  p arti ci p at e i n t h e  n o n-r a n d o  mi z e d  pil ot  c o h ort.   
 
K e y   Eli gi bilit y   C rit e ri a:   
•    Hist ol o gi c  c o nfir  m ati o n  of  a d e n o c ar ci n o  m a  of t h e  pr ost at e   
•    R e c ei vi n g  or  pl a n ni n g t o r e c ei v e   A  D T   wit h  L  H  R  H  a g o nist  or  a nt a g o nist    
•    E x p e ct e d  d ur ati o n  of   A  D T  at l e ast  1 2   m o nt hs fr o  m st u d y  e n tr y 
•    C o n c urr e nt  a nti a n dr o g e n t h er a p y  all o  w e d  b ut  n ot r e q uir e d   
•    First  d os e  of  L  H  R  H  a g o nist  or  a nt a g o nist  n o   m or e t h a n  6   m o nt hs  pri or t o st u d y  e ntr y  
•    Pri or/ c o n c urr e nt r a di ati o n t h er a p y  all o  w e d  
•    P h ysi c all y  a bl e t o  p arti ci p at e i n  e x er cis e  pr o gr a  m  
•    Willi n g  a n d  a bl e t o tr a v el t o   U  C S F f or   m o nt hl y  visits   
•    R a n d o  mi z e d  c o h o rt  o nl y:   
o    N o  pri or  c h e  m ot h er a p y   wit hi n  1 2   m o nt hs  of st art  d at e  of st u d y   
    N o  pl a n n e d  c h e  m ot h er a p y  d uri n g t h e i niti al  1 2   m o nt h  p eri o d  of st u d y 
p arti ci p ati o n   
•    N o n  -r a n d o  mi z e d  pil ot  c o h o rt:  
o   C o n c urr e nt   c h e  m ot h er a p y (i niti at e d   wit hi n  3   m o nt hs  of st u d y  e ntr y)  or  pl a n n e d 
c h e  m ot h er a p y   wit hi n  3   m o nt hs  of st u d y  e ntr y  
 
 
R ati o n al e f or 
St u d y 
A n dr o g e n   d e pri v ati o n t h er a p y (  A  D T) is t h e   m ost  c o  m  m o n s yst e  mi c t h er a p y  a p pli e d i n  pr ost at e 
c a n c er. It is  ass o ci at e d   wit h i  m pr o v e  m e nt i n  o v er all s ur vi v al, r e gr essi o n  of t u  m ors,  a n d s y  m pt o  m 
p alli ati o n i n  v ari o us  dis e as e st at es i n cl u di n g  c o n c urr e ntl y   wit h r a di ati o n t h er a p y, f oll o  wi n g 
s ur g er y,  a n d f or  p ati e nts   wit h   m et ast ati c  dis e as e.   H o  w e v er,   A  D T is  ass o ci at e d   wit h  n u  m er o us 
c h a n g es i n  b o d y  c o  m p ositi o n  a n d   m et a b o li c  p ert ur b ati o ns l e a di n g t o si g nifi c a nt i atr o g e ni c 
m or bi dit y  a n d   m ort alit y  .   A  D T is  ass o ci at e d   wit h t h e  d e vel o p  m e nt  of t h e  m et a b oli c s y n dr o  m e, 
i n cr e as es i n  b o d y f at,  d e cr e as e i n l e a n  b o d y   m a ss, w ei g ht  g ai n,  h y p erli pi d e  mi a, i ns uli n 
r esist a n c e/ di a b et es,  a n d, p ot e nti all y,  a n i n cr e as e d ris k  of  c ar di o v as c ul ar   m or bi dit y  a n d   m ort alit y.  
It  als o i  m p a cts  q u alit y  of lif e  vi a   m us cl e   w asti n g,  h ot fl as h e s,  g y n e c o  m a sti a, s e x u al  d ysf u n cti o n, 
m o o d,  a n d r el ati o ns hi p  c h a n g e s.   Gi v e n t h e  br o a d s p e ctr u  m  of   A  D T  -ass o ci at e d t o xi citi es  a cr oss 
n u  m er o us  d o  m ai ns, t h er e is  a  cl e ar  u n  m et   m e di c al  n e e d t o  d e v el o p s yst e  m ati c,   m ulti -dis ci pli n ar y 
a p pr o a c h t o  p arti all y   miti g at e t h e t o xi cit y  of   A  D T.   
 
M a n y  of   A  D T  -ass o ci at e d t o xi citi es  ar e   m o difi a bl e   wit h  c ar ef ul   m a n a g e  m e nt,  alt h o u g h  c urr e nt 
pr a cti c e  d at a s u g g est t h at t h e  v ast   m aj orit y  of  p h ysi ci a ns   w h o  pr es cri b e   A  D T  d o  n ot   m a n a g e 
t h es e  si d e  eff e cts in  a  c o nsist e nt   w a y, if  at  all.    M ulti pl e  pri or st u di es i n t h e  pri  m ar y  c ar e s etti n g 
d e  m o nstr at e  t h at i nt e gr at e d,   m ulti-dis ci pli n ar y  eff orts  as  c o  m p ar e d t o  r o uti n e  c o u ns eli n g  d uri n g 
p h ysi ci a n  visits l e a d  t o m or e   s u bst a nti al  c h a n g es i n lif est yl e  h a bits, i n cl u di n g i  m pr o v e d  di et, 
s  m o ki n g  c ess ati o n,  a n d  bl o o d  pr ess ur e   m a n a g e  m e nt.  T h er ef or e,  c o  m pr e h e nsi v e   m a n a g e  m e nt  of 
t h e  p ot e nti al  si d e  eff e cts  of   A  D T   wit h t h e  us e  of  a   m ulti-dis ci pli n ar y  cli ni c   m a y i  m pr o v e 
o ut c o  m es  a n d  p arti all y r e v er s e t h e si d e  eff e cts  of   A  D T,  a s  c o  m p ar e d t o  us u al  st a n d ar d  of  c ar e.   
 
T h e  “ S T  A  N  D ( S u p p orti v e  T h er a p y i n  A  N dr o g e n  D  e p ri v ati o n) ”   Cli ni c at   U  C S F  w a s  cr e at e d   f or 
p ati e nts tr e at e d   wit h   A  D T  t o  a d dr ess  a n d   miti g at e t h e  a d v ers e  eff e cts  of  h or  m o n e t h er a p y. T h e 
i nt e nt is t o  pr o vi d e  “ o n e  st o p s h o p pi n g ”  a n d  pr o vi d e  p ati e nt  n a vi g ati o n  a cr oss  a  n u  m b er  of 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  3   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
diff er e nt  di s ci pli n es,  cli ni cs  a n d s er vi c es .  
 
D uri n g t h e  c o urs e  of  a n i nt e gr at e d  visit, t h e  p ati e nt   will  h a v e t h e f oll o  wi n g   p ers o n ali z e d 
ass ess  m e nt  a n d  c o u ns eli n g : 
 
•    P ati e nt  c ar e  a n d  c o u ns eli n g  b y  a tr ai n e d  n urs e  pr a ctiti o n er  a n d/ or  p h ysi ci a n  
•    T  w el v e   m o nt hl y  e d u c ati o n al  “  m o d ul es ” r e g ar di n g   A  D T si d e  eff e ct   m a n a g e  m e nt   
•    M e di c ati o n   m a n a g e  m e nt i n cl u di n g  L  H  R  H  a n al o g u e i nj e cti o ns  d uri n g  visit   
•    C ar di o v as c ul a  r   m o nit ori n g  a n d ris k r e d u cti o n, i n cl u di n g  h y p ert e nsi o n,  h y p erli pi d e  mi a, 
gl u c o s e   m o nit ori n g,  a n d  c ar di a c ris k str atifi c ati o n   
•    B o n e  h e alt h   m o nit ori n g  a n d   m a n a g e  m e nt   
•    N utriti o n  c o u ns eli n g   
•    E x er cis e tr ai ni n g  
•    E v al u ati o n  a n d  c o u ns eli n g f or r el ati o ns hi p  a n d   m o o d  c h a n g e s  b y tr ai n e d s o ci al   w or k er  
•    Ass ess  m e nt  of  q u alit y  of lif e  a n d si d e  eff e cts  of   A  D T   wit h  v ali d at e d  q u esti o n n air es 
( p ati e nts   will  als o  h a v e  o p p ort u nit y t o fill  o ut  q u esti o n n air e s  o n-li n e  a h e a d  of  cli ni c  visit) 
 
T h e  c urr e nt  r a n d o  mi z e d  p h as e  2  cr oss-o v er  st u d y  is  d esi g n e d t o pr eli  mi n ar y  e v al u at e t h e  
l o n git u di n al i  m p a ct  of  p arti ci p ati o n i n t h e  “ S T  A  N  D ”  cli ni c  ( as  c o  m p ar e d t o  us u al st a n d ar d  of 
c ar e)  o n  k e y  m et a b  oli c  p ar a  m et ers,  q u alit y  of lif e,  a n d  p ati e nt s atisf a cti o n  f or   m e n r e c ei vi n g 
h or  m o n e t h er a p y f or  pr ost at e  c a n c er.  St a n d ar d -of -c ar e t h er a p y   will  c o nsist  of  e v er y  3 -m o nt h 
visits  c o  m pris e d  of r e vi e  w  of   m e di c al  hist or y, t o xi cit y  a ss e ss  m e nt,  a n d lif est yl e   m o difi c ati o n 
c o u ns eli n g  pr o vi d e d  b y i n di vi d u al  h e alt h  c ar e  pr o vi d er,  L  H  R  H  a n al o g i nj e cti o ns  b y tr ai n e d  
o n c ol o g y  n ur s e.  P ati e nts   will  h a v e  a c c e ss t o  e x er cis e,  n utriti o n,  a n d s o ci al   w or k  c o u ns eli n g  if 
r e q u est e d  b y  p ati e nt  or  d e e  m e d  n e c ess ar y  aft er  c o ns ult ati o n   wit h  h e alt h  c ar e  pr o vi d er. Aft er  1 2 
m o nt hs  o n st u d y,  p ati e nts r a n d o  mi z e d t o t h e  us u al  st a n d ar d  -of - car e  ar  m  will  h a v e t h e  o p p ort u nit y 
t o  cr oss-o v er  a n d  p arti ci p at e i n t h e  S T  A  N  D  cli ni c f or t h e  e ns ui n g  1 2   m o nt hs  or f or t h e r e  m ai n d er 
of  A  D T  d ur ati o n,   w hi c h e v er is s h ort er.    S h o ul d t h e r es ults i n di c at e  a  b e n efi ci al i  m p a ct  of 
p arti ci p ati o n i n  a   m ulti -dis ci pli n ar y  cli ni c i n   miti g ati n g t h e s h ort - a n d i nt er  m e di at e -t er  m 
t o xi citi e s  of   A  D T, t his   w o ul d f or  m t h e j ustifi c ati o n f or l ar g er r a n d o  mi z e d  cli ni c al tri als t o  ass ess 
t h e i  m p a ct  of  cli ni c  p arti ci p ati o n  o n l o n g er-t er  m  c o-m or bi diti es i n cl u di n g t h e i n ci d e n c e  of 
di a b e t es,  c ar di o v as c ul ar   m or bi dit y  a n d   m ort alit y,  a n d  o v er all i n ci d e n c e  of  n o n-pr ost at e  c a n c er 
s p e cifi c   m ort alit y.   
 
Pri  m ar y 
O bj e cti v e   
R a n d o  mi z e d  c o h o rt:    T o   c o  m p ar e   t h e    m e a n  p er c e nt   c h a n g e  fr o  m  b as eli n e  t o  1 2    m o nt hs  i n 
p er c e nt a g e   b o d y  f at   m ass    a  m o n g    m e n    wit h   pr ost at e  c a n c er  r e c ei vi n g   a n dr o g e n   d e pri v ati o n 
t h er a p y r a n d o  mi z e d t o  p arti ci p at e i n t h e  “ S T  A  N  D ”  cli ni c  vs.  us u al st a n d ar d  of  c ar e.  
 
N o n  -r a n d o  mi z e d  pil ot  c o h o rt:   T o  d et er  mi n e  t h e  f e asi bilit y  of  c o  m pl eti n g    m ulti  -dis ci pli n ar y 
S T  A  N  D  cli ni c  vis its   w hil e  u n d er g oi n g  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y f or  pr ost at e  c a n c er. 
S e c o n d ar y 
O bj e cti v es   
T o   c o  m p a r e  t h e   m e a n  p e r c e nt  c h a n g e  f r o  m  b as eli n e  t o  1 2   m o nt hs  a n d  p att e r ns  of  c h a n g e 
o v e r ti  m e  d u ri n g  p a rti ci p ati o n i n t h e  S  T  A  N  D  cli ni c  vs.  us u al  st a n d a r d  of  c a r e   wit h  r es p e ct 
t o: 
 
M et a b oli c   I  m p a ct  o n   Di a b et es  a n d C ar di o v as c ul ar  Ris k  F a ct ors:    
-   F asti n g  bl o o d  gl u c o s e  
-   F asti n g  pl a s  m a i ns uli n l e v el  
-   I ns uli n r esist a n c e  as  c al c ul at e d  b y   H  O  M  A-I  R 
-   H e  m o gl o bi n   A 1 c   
-   F asti n g li pi ds (t ot al  c h ol est er ol,  L  D L,   H  D L, tri gl y c er ci d es)  
-   W aist  cir c u  mf er e n c e   
-   B o d y   w ei g ht/ b o d y   m ass i n d e x   
-   E x er cis e  p att er ns  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e  a n d  h o  m e -b as e d  a c c el er o  m et er 
ass ess  m e nt   
-   Bl o o d  pr ess ur e   
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  4   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
B o n e   H e alt h:   
-   B o n e  d e nsit y  a s  ass e ss e d  b y   D  X  A  s c a n   
-   2 5 -(  O  H)  vit a  mi n   D  s er u  m l e v els 
 
Q u a  lit y  of Lif e/ Ps y c h os o ci al I  m p a ct:  
-   D e pr essi o n  as   m e as ur e d  b y  P  H  Q  - 9 
-   C o g niti v e f u n cti o n  a s   m e a s ur e d  b y   t h e   Att e nti o n al  F u n cti o n al I n d e x 
-   O v er all  q u alit y  of lif e  a s   m e a s ur e d  b y  S F  -1 2  
-   F ati g u e  as   m e as ur e d  b y  L e e  F ati g u e  S c al e  
-   Er e ctil e  a n d  uri n ar y  f u n cti o n  a s   m e a s ur e d  b y E PI  C -2 6  
-   H ot fl as h s e v erit y  a s   m e a s ur e d  b y   H ot  Fl a s h   R el at e d   D ail y I nt erf e  r en c e  S c al e  
 
 
A  m o n g   m e n  r a n d o  mi z e d t o  r e c ei v e  us u al  st a n d a r d  of  c a r e t h at  c r oss  -o v e r t o  p a rti ci p at e i n 
t h e  S  T  A  N  D  cli ni c  aft e r   m o nt h  1 2  of t h e st u d y: 
 
T o   m e as ur e t h e   m e a n  c h a n g e fr o  m   b as eli n e  at  st art  of  p arti ci p ati o n i n t h e  S T  A  N  D  cli ni c  aft er  1 2 
m o nt hs  of  p arti ci p ati o n i n:    
 
-   M et a b oli c  p ar a  m et ers  i n cl u di n g  p er c e nt a g e  b o d y  f at,  f asti n g  i ns uli n/ gl u c os e,    H  O  M  A  -
I  R, b o d y   w ei g ht/ b o d y   m ass i n d e x,   w aist  cir c u  mf er e n c e  
-   B o n e  h e alt h   
-   Q u alit y  of lif e   
 
A  m o n g   m e n i n t h e  n o n  -r a n d o  mi z e d  pil ot  c o h o rt:  
-   T o   d et er  mi n e  t h e    m e a n  c h a n g e  fr o  m   b as eli n e  t o   1 2    m o nt hs   d uri n g   S T  A  N  D  cli ni c 
p arti ci p ati o n  i n  t h e  pri  m ar y  a n d  s e c o n d ar y    m et a b oli c  a n d  q u alit y  of  lif e  p ar a  m et ers 
list e d  a b o v e. 
C orr el ati v e 
St u d y 
O bj e cti v e  s 
•    T o i n v esti g at e f or  a r el ati o ns hi p  b et  w e e n i n h erit e d  g e n eti c  p ol y  m or p his  ms  of f u n cti o n al 
r el e v a n c e  n e ar  or   wit hi n  g e n es  e n c o di n g  pr ot ei ns   wit h r ol es i n st er oi d  h or  m o n e tr a ns p ort 
a n d  a n dr o g e n  r e c e pt or  si g n ali n g    wit h  c h a n g es  i n    m et a b oli c  p ar a  m et ers  a  m o n g    m e n 
tr e at e d   wit h  a n dr o g e n  d e pri v ati o n t h er a p y.  
•    T o  i n v esti g at e  c h a n g es  i n  tr a b e c ul ar   b o n e    mi cr o  -ar c hit e ct ur e  as    m e as ur e d   b y    Hi g h 
R es ol uti o n  P eri p h er al    Q  C T  I  m a gi n g  of  r a di us  a n d  ti bi a  d uri n g  a n dr o g e n  d e pri v ati o n 
t h er a p y. 
•    T o i n v esti g at e  f or  r el ati o ns hi p  b et  w e e n   2 n d di git t o  4 t h di git l e n gt h  r ati o n  ( 2  D: 4  D  r ati o) 
a n d  p er c e nt  c h a n g e  fr o  m  b as eli n e  i n  q u alit y  of  lif e    m etri cs  o n  a n dr o g e n  d e pri v ati o n 
t h er a p y. 
•    T o i n v esti g at e  f or  a  r el ati o ns hi p  b et  w e e n  2 n d di git t o  4 t h di git l e n gt h  r ati o  a n d  b as eli n e 
e  m p at h y s c or e  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e.  
 
St u d y   D esi g n  
R a n d o  mi z e d,  p h as e  2  st u d y   wit h  cr oss  -o v er  d esi g n  t o  a ss ess t h e l o n git u di n al i  m p a ct  of t h e   m ulti-
dis ci pli n ar y  S T  A  N  D  cli ni c  o n  c h a n g es i n  k e y   m et a b oli c  p ar a  m et ers,  q u alit y  of lif e,  a n d  p ati e nt 
s atisf a cti o n  a  m o n g    m e n  r e c ei vi n g  a n dr o g e n  d e pri v ati o n  t h er a p y  f or  pr ost at e  c a n c er.   A  n o n  -
r a n d o  mi z e d   pil ot   c o h ort   of   p ati e nts   r e c ei vi n g   c o n c urr e nt   c h e  m o h or  m o n al  t h er a p y    will   b e 
e nr oll e d  i n   p ar all el  t o   ass ess  t h e  f e a si bilit y   of   S T  A  N  D   cli ni c   p arti ci p ati o n  i n  t his   p ati e nt 
p o p u l ati o n. 
 
R a n d o  mi z e d st u d y s c h e  m a:   
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  5   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
 
N u  m b er  of 
p ati e nts  
8 0   p ati e nts    wit h  p r ost at e  c a n c er    w h o  ar e  e x p e ct e d  t o  r e c ei v e  at  l e ast  1 2    m o nt hs  of  a n dr o g e n 
d e pri v ati o n t h er a p y  fr o  m t h e  d at e  of st u d y  e nr oll  m e nt will  b e  e nr oll e d  . 
 
A   s e p ar at e   n o n -r a n d o  mi z e d   p ati e nt   c o h ort   of   2 0   p ati e nts     w h o   ar e   r e c ei vi n g   c o n c urr e nt 
c h e  m o h or  m o n al t h er a p y   will  b e  e nr oll e d i n  p ar all el.  
D ur ati o n  of 
st u d y 
P ati e nts   r a n d o  mi z e d  t o  p arti ci p at e  i n  t h e  S T  A  N  D  cli ni c    will  b e  f oll o  w e d  f or  1 2    m o nt hs.    M e n 
i niti all y  r a n d o  mi z e d  t o  t h e   us u al  st a n d ar d-of -c ar e    will   h a v e  t h e   o pti o n  t o   cr oss -o v er   o nt o 
p arti ci p ati o n i n t h e  S T  A  N  D  cli ni c  aft er   m o nt h  1 2,  a n d   will  b e f oll o  w e d i n t h e  S T  A  N  D  cli ni c f or 
a n  a d diti o n al  1 2    m o nt hs  or  u ntil  6    m o nt hs  f oll o  wi n g  l ast  d os e  of    A  D T,    w hi c h e v er  is  s h ort er . 
P ati e nts  e nr oll e d i n t h e  n o n -r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort   will  p arti ci p at e i n  S T  A  N  D  cli ni c 
f or  1 2   m o nt hs.    
    
St u d y  
Ass ess  m e nts   
I n  t h e   S T  A  N  D  cli ni c tr e at  m e nt ar  m,  p ati e nts   will  h a v e  e v er y  3    m o nt h  visits   wit h  a  h e alt h  c ar e 
pr o vi d er,   al o n g    wit h   m o nt  hl y   e d u c ati o n al    m o d ul es,   a n d   m ulti  -dis ci pli n ar y   a ss e ss  m e nt   a n d 
c o u ns eli n g  b y  e x er cis e,  n utriti o n,  a n d  s y  m pt o  m    m a n a g e  m e nt  s er vi c e  o n  a  r ot ati n g  s c h e d ul e.  I n 
t h e  us u al  c ar e tr e at  m e nt  ar  m,  p ati e nts   will  h a v e  e v er y  3   m o nt h  visits   wit h t h eir us u al  h e alt h  c ar e 
pr o vi d er,  a n d    will  h a v e  u nr e stri ct e d  a c c ess  t o  e x er cis e,  n utriti o n,  a n d  s y  m pt o  m    m a n a g e  m e nt 
s er vi c es  u p o n  p ati e nt  r e q u est  or  as  d e e  m e d   n e c ess ar y  b y   h e alt h  c ar e  pr o vi d er.   I n  t h e   n o n-
r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort,  p ati e nts   will  h a v e  s c h e d ul e   m odifi e d  a s  n e c ess ar y t o fit   wit h 
c h e  m ot h er a p y  d osi n g  s c h e d ul e  b ut   will  h a v e  o n  a v er a g e  e v er y  3   m o nt h  c o u ns eli n g   wit h  p h ysi c al 
t h er a pist,  n utriti o n,  a n d s y  m pt o  m   m a n a g e  m e nt. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  6   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
St u d y 
E n d p oi nts 
P ri  m a r y   E n d p oi nt  
 
R a n d o  mi z e d  c o h ort:   
M e a n  p er c e nt   c h a n g e  fr o  m  b as eli n e  t o  1 2    m o nt hs  i n  p er c e nt a g e  b o d y  f at   m a ss  a s   m e as ur e d  b y 
bi o el e ctri c al i  m p e d a n c e  a n al y z er.   
 
N o n  -r a n d o  mi z e d  c o h ort: 
P er c e nt a g e  of  c o  m pl et e d  S T  A  N  D  cli ni c  visits  d uri n g t h e  c o urs e  of t h e  1 2   m o nt h  S T  A  N  D  cli ni c 
p arti ci p ati o n.  
 
S e c o n d a r y   E n d p oi nts  
M e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e  t o  1 2    m o nt hs  a n d  p att er ns  of  c h a n g e  fr o  m  b as eli n e    wit h 
r es p e ct t o t h e f oll o  wi n g: 
 
M et a b oli c   I  m p a ct  o n   Di a b et es  a n d C ar di o v as c ul ar   Dis e as e   Ris k  F a ct ors:   
-   F asti n g  bl o o d  gl u c o s e  
-   F asti n g  pl a s  m a i ns uli n l e v el  
-   I ns uli n r esist a n c e  as  c al c ul at e d  b y   H  O  M  A-I  R 
-   H e  m o gl o bi n   A 1 c   
-   F asti n g li pi ds (t ot al  c h ol est er ol,  L  D L,   H  D L, tri gl y c er ci d es)  
-   W aist  cir c u  mf er e n c e   
-   B o d y   w ei g ht/ b o d y   m ass i n d e x   
-   E x er cis e  p att er ns  as   m e a s ur e d  b y  v ali d at e d  q u esti o n n air e  a n d  a  m b ul at or y  a c c el er o  m et er 
ass ess  m e nt  
-   Bl o o d  pr ess ur e   
 
B o n e   H e alt h:   
-   B o n e  d e nsit y   at t h e l u  m b ar  s pi n e, f e  m or al  n e c k,  a n d t ot al  hi p  as  ass ess e d  b y   D  X  A  s c a n  
a  m o n g  p ati e nts   wit h o ut  b o n e   m et ast as es  at t h e ti  m e  of  st u d y  e ntr y  
-   S er u  m  2 5 -(  O  H)  vit a  mi n   D l e v els 
 
Q u alit y  of  Lif e/ Ps y c h os o ci al I  m p a ct:   
-   D e pr essi o n  as   m e as ur e d  b y  P  H  Q  - 9 
-   C o g niti v e f u n cti o n  a s   m e a s ur e d  b y   Att e nti o n al  F u n cti o n al I n d e x   
-   O v er all  q u alit y  of lif e  a s   m e a s ur e d  b y  S F  -1 2  
-   F ati g u e  as   m e as ur e d  b y  L e e  F ati g u e  S c al e  
-   Er e ctil e  a n d  uri n ar y f u n cti o n  a s   m e a s ur e d  b y  E PI  C -2 6  
-   H ot fl as h s e v erit y  a s   m e a s ur e d  b y   H ot  Fl a s h   R el at e d   D ail y I nt erf er e n c e  S c al e   
 
C o r r el ati v e  St u d y   E n d p oi nt  s: 
•    Ass o ci ati o n  b et  w e e n  i n h erit e d  g e n eti c  p ol y  m or p his  ms  of  f u n cti o n al  r el e v a n c e  n e ar  or 
wit hi n  g e n es  e n c o di n g  pr ot ei ns    wit h  r ol es  i n  st er oi d  h or  m o n e  tr a ns p ort  a n d  a n dr o g e n 
r e ce pt or  si g n ali n g    wit h   c h a n g es  i n    m et a b oli c   p ar a  m et ers   a  m o n g    m e n  tr e at e d    wit h 
a n dr o g e n  d e pri v ati o n t h er a p y . 
•  
M e a n  c h a n g e  fr o  m  b as eli n e   i n  tr a b e c ul ar  b o n e  ar c hit e ct ur e  as    m e a s ur e d  b y  tr a b e c ul ar 
b o n e  n u  m b er  ( T b  N)  a n d tr a b e c ul ar  b o n e  v ol u  m e  fr a cti o n  (  B  V/ T  V)  aft e r  1 2   m o nt hs  of 
a n dr o g e n  d e pri v ati o n t h er a p y.  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  7   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
Li st  of   A b b r e vi ati o n s  
 
A E         
A d v ers e  e v e nt   
C  H  R         
C o  m  mitt e e  o n   H u  m a n   R es e ar c h (  U  C S F I R  B)   
C  R  C         
Cli ni c al   R es e ar c h   C o or di n at or   
C T  M S      
Cli ni c al  Tri al   M a n a g e  m e nt  S yst e  m   
D S  M  C      
D at a  a n d  S af et y   M o nit ori n g   C o  m  mitt e e   
D S  M P      
D at a  a n d  S af et y   M o nit ori n g  Pl a n   
F  D  A         
F o o d  a n d   Dr u g   A d  mi nistr ati o n 
G  C P         
G o o d   Cli ni c al  Pr a cti c e   
H  D F  C  C  C     
H el e n   Dill er  F a  mil y   C o  m pr e h e nsi v e   C a n c er   C e nt er   
I  C  H        
I nt er n ati o n al   C o nf er e n c e  o n   H ar  m o ni z ati o n 
I  R  B       
I nstit uti o n al   R e vi e  w   B o ar d 
N  CI         
N ati o n al   C a n c er I nstit  ut e 
P  R  C        
Pr ot o c ol   R e vi e  w   C o  m  mitt e e (  U  C S F)  
 
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  8   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
T a bl e  of  C o nt e nt s  
Pr ot o c ol  Si g n at ur e  P a g e  ...................................................................................................  2 
A B S T R A C T  ........................................................................................................................  3 
Li st  of  A b br e vi ati o n s  ........................................................................................................  8 
1.  B a c k g r o u n d  a n d  R ati o n al e .......................................................................................... 1 2  
1. 1  St u d y  R ati o n al e  a n d  Cli ni c al  Si g nifi c a n c e  ............................................................................... 1 2  
1. 2  R ati o n al e f or t h e  Cli ni c al  St u d y  E n d p oi nts  ............................................................................. 1 4  
2.  H y p ot h esi s  a n d  St u d y   O bj e cti v es  ................................................................................ 2 0  
2. 1  H y p ot h esi s  ........................................................................................................................... 2 0  
2. 2  St u d y   O bj e cti v es ................................................................................................................... 2 0  
 
3.  St u d y  D esi g n  ........................................................................................................................ 2 3  
3. 1   O v er all  St u d y  C h ar a ct eri sti c s  ................................................................................................ 2 3  
3. 2  St u d y  E n d p oi nts  ................................................................................................................... 2 3  
3. 3  St u d y  Sc h e  m a  ....................................................................................................................... 2 5  
4.  St u d y  P o p ul ati o n  ........................................................................................................ 2 6  
4. 1 I n cl usi o n  Crit eri a  .................................................................................................................. 2 6  
4. 2  E x cl usi o n  Crit eri a  .................................................................................................................. 2 7  
5. 1    L u p r o n   D e p ot (  L e u p r oli d e  a c et at e f o r  d e p ot s us p e nsi o n)   D es c ri pti o n,  F o r  m ul ati o n 
a n d   St o r a g e  .............................................................................................................. 2 8  
5. 1. 1    D es c ri pti o n  .......................................................................................................... 2 8  
5. 1. 2  F o r  m ul ati o n  ......................................................................................................... 2 8  
5. 1. 3  St o r a g e  ................................................................................................................. 2 8  
5. 2. 2  F o r  m ul ati o n  ......................................................................................................... 2 8  
5. 2. 3  St o r a g e  ................................................................................................................. 2 8  
5. 3. 1    D es c ri pti o n  .......................................................................................................... 2 9  
5. 3. 2  F o r  m ul ati o n  ......................................................................................................... 2 9  
5. 3. 3  St o r a g e  ................................................................................................................. 2 9  
5. 4      T elst a r   D es c ri pti o n,  F o r  m ul ati o n,  a n d  St o r a g e  .................................................... 2 9  
5. 4. 1   D es c ri pti o n  ........................................................................................................... 2 9  
5. 4. 2  F o r  m ul ati o n  ......................................................................................................... 2 9  
5. 4. 3  St o r a g e  ................................................................................................................. 2 9  
6.  Dr u g  Tr e at  m e nt  Pl a n  .................................................................................................. 3 0  
6. 1   L  H  R  H   R o ut e  of   A d  mi nist r ati o n,  P ri  m a r y  Si d e   Eff e cts,  a n d   D os e   M o difi c ati o ns  a n d 
D osi n g   D el a ys   ........................................................................................................... 3 0  
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E  9   O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
6. 1. 1    R o ut e  of   A d  mi nist r ati o n  ...................................................................................... 3 0  
6. 1. 2  P ri  m a r y  Si d e   Eff e cts  ............................................................................................ 3 0  
7.  St u d y  A cti viti es  .......................................................................................................... 3 1  
7. 1  St u d y  Sc h e d ul e  ..................................................................................................................... 3 1  
7. 2  S cr e e ni n g  Visit (  wit hi n  6   w e e ks  of  D a y  1  of  St u d y)  ................................................................. 3 3  
7. 3  R a n d o  miz ati o n  ..................................................................................................................... 3 4  
7. 4  D a y  1  St u d y  Visit  .................................................................................................................. 3 4  
7. 5  D a y  1  a n d   M o nt hl y  St u d y  Vi sit s ( + / - 2   w e e ks)  ........................................................................ 3 4  
7. 6  E v er y  3   M o nt h  St u d y  Vi sits ( + / - 2   w e e ks)  .............................................................................. 3 5  
7. 7  E n d  of   M o nt h  1 2  St u d y  Vi sit ( + / - 2   w e e ks)  ............................................................................. 3 6  
7. 8  C o n c o  mit a nt   M e di c ati o ns  ..................................................................................................... 3 7  
7. 9  F oll o  w   U p  ............................................................................................................................. 3 7  
7. 1 0  D ur ati o n  of  St u d y  ............................................................................................................... 3 7  
8.  A ss ess  m e nt  of  St u d y  V ari a bl es  ................................................................................... 3 8  
8. 1  P er c e nt  B o d y  F at  Esti  m ati o n  ................................................................................................. 3 8  
8. 2  P ati e nt -R e p ort e d   O ut c o  m es  ................................................................................................. 3 8  
8. 3  G er  mli n e  P ol y  m or p hi s  ms ...................................................................................................... 3 8  
8. 4  Hi g h  R es ol uti o n  P eri p h er al   Q u a ntit ati v e  C T I  m a gi n g   .............................................................. 3 9  
 
9.  Pl a n n e d  St ati sti c al   M et h o d s  ....................................................................................... 4 1  
9. 1  St u d y  D esi g n  ........................................................................................................................ 4 1  
9. 2  D et er  mi n ati o n  of  S a  m pl e  Siz e  a n d  St u d y  P o  w er  .................................................................... 4 1  
9. 3 I nt eri  m  A n al y si s  ................................................................................................................... 4 2  
9. 4  A c cr u al  ................................................................................................................................. 4 2  
9. 5  A n al y si s  P o p ul ati o ns  ............................................................................................................. 4 2  
9. 6  D e  m o gr a p hi cs  a n d  B as eli n e  C h ar a ct eri sti cs   ........................................................................... 4 3  
9. 7   St u d y  E n d p oi nts ................................................................................................................... 4 3  
9. 8   M et h o ds f or  A n al ysis  ............................................................................................................ 4 4  
1 0.  St u d y   M a n a g e  m e nt  .................................................................................................. 4 7  
1 0. 1  Pr e -st u d y  D o c u  m e nt ati o n  ....................................................................................... 4 7  
1 0. 2 I nstit uti o n al  R e vi e  w  B o ar d  A p pr o v al  ................................................................................... 4 7  
1 0. 3 I nf or  m e d  C o ns e nt  ............................................................................................................... 4 7  
1 0. 4  C h a n g es i n t h e  Pr ot o c ol  ...................................................................................................... 4 8  
1 0. 5  C as e  R e p ort  F or  ms ( C R Fs)  ................................................................................................... 4 8  
1 0. 6  R et e nti o n  of  R e c or ds  .......................................................................................................... 4 9  
1 1.  R ef er e n c es  ............................................................................................................... 5 0  
A p p e n di x  1.  S el e ct e d  G e n eti c  P ol y  m or p hi s  ms  ................................................................ 5 2  
A p p e n di x  2.   Q u alit y  of  Lif e   Q u e sti o n n ai r e s   ........................................................................... 5 3  
A p p e n di x  3.  C h arl s o n  C o -M or bi dit y I n d e x   ...................................................................... 6 6  
A p p e n di x  4:  Bi o el e ctri c al I  m p e d a n c e  D e vi c e f or  A ss ess  m e nt  of  P er c e nt a g e  B o d y  F at   ...... 6 7  
A p p e n di x  5:  A c c el er o  m et er  F or  A  m b ul at or y  R e c or di n g  of  A cti vit y  L e v el s  ........................ 6 8  
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x  6.   D at a  a n d  S af et y   M o nit ori n g  Pl a n  f or  a  P h as e  2 I n stit uti o n al  St u d y .............. 6 9  
A p p e n di x  7.  S p e ci  m e n  H a n dli n g  a n d  St or a g e  .................................................................. 7 0  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1.  B a c k g r o u n d   a n d   R ati o n al e 
 
1. 1  St u d y   R ati o n al e  a n d   Cli ni c al  Si g nifi c a n c e  
A n dr o g e n  d e pri v ati o n t h er a p y   (  A  D T), i n   w hi c h t h e  cir c ul ati n g  s er u  m t est ost er o n e is r e d u c e d t o  a 
c ast rat e -r a n g e  (l ess  t h a n  5 0  n g/ d L),  is  a  st a n d ar d  tr e at  m e nt  o pti o n  f or  p ati e nts    wit h  pr ost at e 
c a n c er  a cr oss  a  v ari et y  of  dis e as e st at es, i n cl u di n g  a dj u v a nt t h er a p y f or l o c ali z e d  dis e as e,  a risi n g 
P S  A  aft er s u r g er y  a n d/ or r a di ati o n t h er a p y, a n d f or r a di o gr a p hi c all y  d et e ct a bl e   m et ast ati c  dis e as e 
t o  t h e  b o n es  a n d  ot h er  or g a ns.  A  D T   r e pr es e nts  t h e    m ost  c o  m  m o n  s yst e  mi c  t h er a p y  a p pli e d  i n 
pr ost at e  c a n c er  a n d  n e arl y  4 0  %  of   m e n   will r e c ei v e   A  D T   wit hi n  6   m o nt hs  of r e c ei vi n g  pr ost at e 
c a n c er  di a g n osis.   T h o u g h  i niti all y  eff e cti v e  i n  t h e    m aj orit y  of  p ati e nts   i n  l o  w eri n g  t h e  s er u  m 
P S  A  a n d  c o ntr olli n g  or  pr e v e nti n g  dis e as e  pr o gr essi o n,   A  D T  is  ass o ci at e d   wit h   a   m ultit u d e  of  
c li ni c all y  si g nifi c a nt   y et   p ot e nti all y  tr e at a bl e  t o xi citi es.    T h es e  i n cl u d e   si d e  eff e cts  t h at  c a n  
a d v ers el y  a ff e ct  q u alit y  of lif e s u c h  as  h ot fl as h es, f ati g u e,  d e cr e as e d li bi d o,  er e ctil e  d ysf u n cti o n , 
g y n e c o  m asti a,  a n d    m o o d/ c o g niti v e  c h a n g es,   w hi c h  c a n  a d v ers el y  i  m p a ct  p ati e nts’  r el ati o ns hi p 
wit h  s p o us e,  f a  mil y    m e  m b ers,  a n d  c ar e gi v ers.    A  D T  is  ass o ci at e d    wit h  si g nifi c a nt    m et a b oli c 
t o xiciti es  i n cl u di n g i n cr e as e d  ris k  of i ns uli n  r esist a n c e  a n d  di a b et es, i n cr e as e i n  b o d y  f at, l o  w er 
b o d y   m ass,  a n d  d e cr e as e d  b o n e   mi n er al  d e nsit y ,  a n d i n cr e as e d ris k f or  ost e o p or oti c fr a ct ur es [ 1-
7 ]. T h e  d e v el o p  m e nt  of t h e   m et a b oli c  a n d  c ar di a c ris k f a ct ors  o n   A  D T  c a n  p ar a d o xi c all y s h ort e n, 
r at h er t h a n  e xt e n d, t h e lif e s p a n  of   m e n   wit h  pr ost at e  c a n c er.  
M a n y  of t h es e  c h a n g es  ar e   m o difi a bl e   wit h  c ar ef ul   m a n a g e  m e nt,  alt h o u g h  c urr e nt  pr a cti c e  d at a 
s u g g est t h at t h e  v ast   m aj orit y  of  p h ysi ci a ns   w h o  pr es cri b e   A  D T  d o  n ot   m a n a g e t h es e  si d e  eff e cts 
i n  a  c o nsist e nt   w a y, if  at  all. A  pri or  pil ot  st u d y i n   w hi c h  p ati e nts r e c ei v e d  a  n o n  -i n di vi d u ali z e d 
e d u c ati o n al   “t o ol -kit ”   c o nt ai ni n g   i nf or  m ati o n   a n d   r e c o  m  m e n d ati o ns     wit h   r es p e ct   t o   di et, 
e x er cis e,   a n d   ot h er   lif est yl e     m o difi c at i o ns   a  m o n g     m e n   st arti n g     A  D T    i  m pr o v e d   p ati e nts 
s atisf a cti o n  an d  l e d  t o  p arti al  lif est yl e  c h a n g es;  h o  w e v er  p ati e nt  r et e nti o n  o n  t h e  pr o gr a  m   w as 
i n c o  m pl et e  i n  p art  d u e  t o  l a c k  of  i n di vi d u ali z e d  c o u ns eli n g  [ 8].  I n di vi d u ali z e d,  c o  m pr e h e nsi v e 
m a n a g e  m e nt  of t h e  p  ot e nti al  si d e  eff e cts  of   A  D T   wit h t h e  us e  of  a   m ulti -dis ci pli n ar y  cli ni c  wit h 
“f a c e -t o-f a c e ”   c o u ns eli n g  pr o vi d e d   b y   s p e ci alists   a cr oss  r el e v a nt   dis ci pli n es   m a y   b e    m or e 
eff e cti v e  i n  pr o  m oti n g  d ur a bl e  c h a n g es  i n  lif est yl e  f a ct ors  a n d  p ot e nti all y    miti g ati n g   th e  si d e 
eff e cts  of   A  D T,  as  c o  m p a r e d t o  us u al  st a n d ar d  of  c ar e  or  n o n-i n di vi d u ali z e d  e d u c ati o n al  h a n d-
o uts/  m at eri als.   M ulti pl e   pri or   st u di es  i n  t h e   pri  m ar y   c ar e   s etti n g   d e  m o nstr at e  t h at     hi g h er 
i nt e nsit y,   i n di vi d u ali z e d   c o u ns eli n g,   as   c o  m p ar e d   t o    l ess   i nt e nsi v e   c o u ns eli n g   i n cl u di n g 
a ut o  m at e d    w e b -  or  t el e p h o n e -b as e d   pr o gr a  ms ,  l e a d  t o    m or e  s u bst a nti al  c h a n g es  i n  lif est yl e 
h a bits,  i n cl u di n g  i  m pr o v e d  di et,   w ei g ht  r e d u cti o n,  a n d  s  m o ki n g  c ess ati o n , a n d    m a y  i n  f a ct  b e 
m or e  c ost  -eff e cti v e   w h e n  c o nsi d eri n g t h e i  m pr o v e m e nt i n  r at es  of  c o  -m or bi dit y  ass o ci at e d   wit h 
hi g h er  i nt e nsit y   c o u ns eli n g   [ 9 - 1 1].   I n    m e n  i niti ati n g    A  D T,   pr os p e cti v e   p arti ci p ati o n  i n   a 
str u ct ur e d  cli ni c  f o c us e d  o n    miti g ati n g  t h e    m et a b oli c  si d e  eff e cts  of  t h er a p y  h as  pr o v e n  t o  b e 
f e asi bl e  a n d  t o  p ot e nti all y  l ess e n   w ei g ht  g ai n,  pr e v e nt  d e c a y  i n  b o n e  d e nsit y/ b o n e  h e alt h,  a n d 
miti g at e  a d v ers e  eff e cts  o n  f asti n g  li pi ds  i n   a  r e c e ntl y  r e p ort e d   A ustr ali a n  o bs er v ati o n al  st u d y 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
[ 1 2].   T h us,  t h er e  is  a  str o n g  r ati o n al e  t o  dir e ctl y  c o  m p ar e  p arti ci p ati o n  i n  a  m ulti  - dis ci pli n ar y 
cli ni c    wit h  st a n d ar d - of-c ar e   p h ysi ci a n   visits   i n  a  r a n d o  mi z e d  f as hi o n  a  m o n g    m e n  r e c ei vi n g 
a n dr o g e n  d e pri v ati o n  t h er a p y,  t o  ass ess    w h et h er  cli ni c  p arti ci p ati o n  l e a ds  t o  i  m pr o v e  m e nts  i n 
m et a b oli c t o xi citi es  ass o ci at e d   wit h t his t h er a p y.    
T h e  “ S T  A  N  D  ( S u p p orti v e   T h er a p y i n   A  N dr o g e n   D e pri v ati o n) ”   Cli ni c  at   U  C S F   w as  cr e at e d  f or 
p ati e nts tr e at e d   wit h   A  D T t o  a d dr ess  a n d   miti g at e t h e  a d v ers e  eff e cts  of  h or  m o n e t h er a p y.   T h e 
i nt e nt  is  t o  pr o vi d e  “ o n e  st o p  s h o p pi n g ”  a n d  i n di vi d u ali z e d  c o u ns eli n g  a n d   t h er a p y  a cr oss  a 
n u  m b er  of  diff er e nt  dis ci pli n es,  cli ni cs  a n d  s er vi c es.  D uri n g t h e  c o urs e  of  a n i nt e gr at e d  visit, t h e 
p ati e nt   will  h a v e t h e f oll o  wi n g  p ers o n ali z e d  ass ess  m e nt  a n d  c o u ns eli n g: 
•    P ati e nt  c ar e  a n d  c o u ns eli n g  b y tr ai n e d  p h ysi ci a n  or  n urs e  pr a ctiti o n er  
•    N utriti o n  c o u ns eli n g   wit h tr ai n e d  di etiti a n   
•    E x er cis e tr ai ni n g  wit h   c ertifi e d  e x er cis e tr ai n er   wit h  e x p ertis e i n  c a n c er  p ati e nts  
•    M e di c ati o n   m a n a g e  m e nt i n cl u di n g  L  H  R  H  a n al o g u e i nj e cti o ns    
•    C ar di o v as c ul ar    m o nit ori n g  a n d  ris k  r e d u cti o n,  i n cl u di n g  h y p ert e n  si o n,  h y p erli pi d e  mi a, 
gl u c os e   m o nit ori n g,  a n d  c ar di a c ris k str atifi c ati o n   
•    B o n e  h e alt h   m o nit ori n g  a n d   m a n a g e  m e nt 
•    E v al u ati o n  a n d  c o u ns eli n g  f or  r e g ar di n g  s y  m pt o  ms  a n d  r el ati o ns hi p  a n d    m o o d  c h a n g es 
b y  s y  m pt o  m   m a n a g e  m e nt s er vi c e  
•    Ass ess  m e nt  of  q u alit y  of lif e   a n d si d e  eff e cts  of   A  D T   wit h  v ali d at e d  q u esti o n n air es  
 
T h e   c urr e nt  r a n d o  mi z e d   p h as e   2   cr oss -o v er  st u d y  is   d esi g n e d  t o   pr eli  mi n ar y   e v al u at e  t h e 
l o n git u di n al i  m p a ct  of  p arti ci p ati o n i n t h e   “ S T  A  N  D ”  cli ni c  ( as  c o  m p ar e d t o  us u al  st a n d ar d  of 
c ar e)  o n  k e y    m et a b oli c  p ar a  m et ers,  q u alit y  of  lif e,  a n d  p ati e nt  s atisf a cti o n  f or    m e n  r e c ei vi n g 
h or  m o n e t h er a p y f or  pr ost at e  c a n c er.   Aft er  1 2   m o nt hs  o n  st u d y,  p ati e nts r a n d o  mi z e d t o t h e  us u al 
st a n d ar d- of-c ar e  tr e at  m e nt  ar  m    will  h a v e  t h e  o p p ort u nit y  t o  cr oss -o v er  a n d  p arti ci p at e  i n  t h e 
S T  A  N  D  cli ni c  f or  t h e  e ns ui n g  1 2   m o nt hs  or  f or  t h e  r e  m ai n d er  of   A  D T  d ur ati o n,   w hi c h e v er  is 
s h ort er.    S h o ul d  t h e  r es ults  i n di c at e  a  b e n efi ci al  i  m p a ct  of  p arti ci p ati o n  i n  a    m ulti -dis ci pli n ar y 
cli ni c  i n    miti g ati n g  t h e  s h ort -  a n d  i nt er  m e di at e -t er  m  t oxi citi es  of    A  D T,  t his    w o ul d  f or  m  t h e 
j ustifi c ati o n  f or  l ar g er  r a n d o  mi z e d  cli ni c al  tri als  t o  ass ess  t h e  i  m p a ct  of  cli ni c  p arti ci p ati o n  o n 
l o n g er-t er  m  c o-m or bi diti es  i n cl u di n g  t h e  i n ci d e n c e  of  di a b et es,  c ar di o v as c ul ar    m or bi dit y  a n d 
m ort alit y,  a n d  o v er all i n ci d e n c e  of  n o n-  pr ost at e  c a n c er s p e cifi c   m ort alit y.   
 
A  s e p ar at e  n o n  -r a n d o  mi z e d  c o h ort  of  p ati e nts r e c ei vi n g  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y   will 
b e  e nr oll e d  t o  ass ess  t h e  f e asi bilit y  of  S T  A  N  D  cli ni c  p arti ci p ati o n  a  m o n g  p ati e nts  r e c ei vi n g 
c h e  m ot h er a p y f or  pr ost at e  c a n c er.  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1. 2  R ati o n al e f o r t h e   Cli ni c al  St u d y   E n d p oi nts 
1. 2 . 1   R ati o n al e f o r t h e  P ri  m a r y   E n d p oi nt 
T h e  pri  m ar y  e n d p oi nt  of t h e  c urr e nt  st u d y   will  b e t h e   m e a n   p er c e nt  c h a n g e  fr o  m  b as eli n e  t o  1 2 
m o nt hs  i n   p er c e nt a g e  b o d y  f at    m ass  as  c al c ul at e d  b y  bi o el e ctri c al  i  m p e d e n c e  a n al y z er.  Pri or 
l o n git u di n al st u di es  h a v e  d e  m o nstr at e d  a  c o nsist e nt   m e a n  p er c e nt a g e  i n cr e as e i n  p er c e nt a g e  f at 
m as  s  of  1 1- 1 2%   ( +/-  1. 5  %)  aft er  1  y e ar  of  a n dr o g e n  d e pri v ati o n  t h er a p y   [ 1 3]. Cr  oss- s e cti o n al 
i  m a gi n g st u di es  h a v e s h o  w n  a str o n g  c orr el ati o n   wit h  p er c e nt a g e  b o d y f at i n cr e as es  o n   A  D T   wit h 
i n cr e as es i n  pr e d o  mi n a ntl y  s u b c ut a n e o us  a di p os e tiss u e. I n cr e as es i n  b o d y f at   m ass  d uri n g   A  D T 
ar e  str o n gl y  ass o ci at e d   wit h  ot h er ris k f a ct ors f or  d i a b et es  a n d  c ar di o v as c ul ar  dis e as e, i n cl u di n g 
d ysli pi d e  mi a,   i ns uli n   r esist a n c e,   a n d   o b esit y .  R es ults   o bt ai n e d   vi a   us e   of   a   bi o el e ctri c al 
i  mp e d e n c e  a n al y z er  c orr el at e   wit h t h e  us e  of  ot h er  p er c e nt  b o d y f at  ass ess  m e nts, i n cl u di n g  d u al 
e n er g y   X -r a y  a bs or pti o  m etr y (  D E  X  A)  a n d  u n d er  w at er   w ei g hi n g   m et h o d ol o gi es,  a n d i ntr a-p ati e nt 
v ari a bilit y is l o  w  [ 1 4].  
M e as uri n g  p er c e nt a g e  b o d y  f at   wit h  h a n d h el d  bi o el e ctri c al  i  m p e d a n c e  d e vi c e  t h us  r e pr es e nts  a 
r e a dil y  o bt ai n a bl e,  f e asi bl e,  a n d  cli ni c all y  r el e v a nt   m ar k er  of t h e  m et a b oli c i  m p a ct  of  a n dr o g e n 
d e pri v ati o n  t h er a p y.  It  is  h y p ot h esi z e d  t h at  c o  m pr e h e nsi v e    m ulti -dis ci pli n ar y  c o u ns eli n g    m a y 
pr o  m ot e  s ust ai n e d  lif est yl e  c h a n g es    wit h  r es p e ct  t o   di et  a n d  e x er cis e    w hi c h    m a y   p arti all y 
miti g at e t h e  a d v ers e   m et a b oli c i  m p a ct  of   A  D T   o n  p er c e nt  b o d y f at,  a n d i n t ur n,  d e cr e as e t h e ris k 
of  l o n g er  t er  m    m et a b oli c   d er a n g e  m e nts  i n cl u di n g  i n ci d e n c e   of   di a b et es   a n d   c ar di o v as c ul ar 
m or bi dit y  a n d   m ort alit y.     
1. 2 . 2 R ati o n al e f o r t h e I n cl usi o n  of   A d diti o n al   M et a b oli c   E n d p oi nts   
Pri or   pr os p e cti v e  l o n git u di n al   st u di es   h a v e   c h ar a ct eri z e d  t h e   p ot e nti al  i  m p a ct   of   a n dr o g e n 
d e pri v ati o n  t h er a p y  o n    m et a b oli c  ris k  f a ct ors  f or  c ar di o v as c ul ar  dis e as e  a n d  di a b et es.    A  m o n g 
t h es e i n cl u d e  c o nsist e nt i n cr e as es i n f asti n g  pl as  m a i ns uli n  a n d i ns uli n r esist a n c e  as   m e as ur e d  b y 
t h e    H o  m e ost ati c    M o d el  (  H  O  M  A-I  R),  i n cr e as es  i n   h e  m o gl o bi n    A 1 c,   d ysli pi d e  mi a  i n cl u di n g 
i n cr e as es  i n  t ot al  c h ol est er ol  a n d  s er u  m  tri gl y c eri d es,  as   w ell  as  c h a n g es  i n  b o d y  c o  m p ositi o n 
i n cl u di n g  i n cr e as e  i n  b od y    w ei g ht,    w aist  cir c u  mf er e n c e   [ 1 3, 1 5].  I n cr e as es  i n  h e  m o gl o bi n   A 1 c 
a n d  ot h er    m ar k ers  of  i ns uli n  r esist a n c e  d uri n g    A  D T  ar e  oft e n  cli ni c all y  si g nifi c a nt;  a n dr o g e n 
d e pri v ati o n  t h er a p y    w as  ass o ci at e d    wit h  a n  i n cr e as e d  ris k  of  t h e  d e v el o p  m e nt  of  di a b et es  o n 
m ulti v ari at e  a n al ysis  i n  pri or  l ar g e  r etr os p e  cti v e  st u d y  [ 7].   E v er y  1  %  i n cr e as e  i n  h e  m o gl o bi n 
A 1  C   w as  ass o ci at e d   wit h  i n cr e as e d  ris k  of    mi cr o v as c ul ar  c o  m pli c ati o ns  i n cl u di n g  r eti n o p at h y,   
n e p hr o p at h y,  a n d  n e ur o p at h y [ 1 6 ].   T h e   H  O  M  A-I  R i n d e x is  str o n gl y  ass o ci at e d   wit h  s u bs e q u e nt 
ris k  of  d e v el o pi n g  di a bet es  a n d  c ar di o v as c ul ar  dis e as e  i n  pri or pr os p e cti v e  st u di es [ 1 7] .   W h et h er 
or  n ot  t h e  i  m p a ct  of    A  D T  o n  t h es e    m et a b oli c  p ar a  m et ers  tr a nsl at es  i nt o  a n  i n cr e as e d  ris k  of 
c ar di o v as c ul ar   m ort alit y is  u n cl e ar   wit h  pri or  st u di es  pr o vi d e d   mi x e d  e vi d e n c e.  M e as uri n g   t h es e 
a d diti o n al  e n d p oi nts  is  li k el y  t o  pr o vi d e  a    m or e  c o  m pr e h e nsi v e  ass ess  m e nt  of  t h e  i  m p a ct  of 
p arti ci p ati o n  i n  t h e   S T  A  N  D   cli ni c   o n  t h e    m et a b oli c  t o xi citi es   of   a n dr o g e n   d e pri v ati o n,   as 
c o  m p ar e d t o   m e as ur e  m e nt  of  c h a n g es i n  p er c e nt a g e  b o d y f at  al o n e.   
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1 . 2. 3   B o n e   H e alt h  
F or   m e n   wit h o ut  b o n e   m et ast as es  at t h e ti  m e  of st u d y  e ntr y, t h e   m e a n  c h a n g e fr o  m  b as eli n e t o  1 2 
m o nt hs i n  b o n e   mi n er al  d e nsit y  as  ass ess e d  b y   D  X  A  s c a n   will  b e  a  s e c o n d ar y  st u d y  e n d p oi nt i n 
t h e  c urr e nt  o bs er v ati o n  st u d y.  N u  m er o us   pri or   st udi es  h a v e  c h ar a ct eri z e d  t h e  d e c li n e  i n  b o n e 
mi n er al   d e nsit y   o bs er v e d    wit h   a n dr o g e n   d e pri v ati o n  t h er a p y.   I n   a   pri or   r a n d o  mi z e d  tri al 
c o  m p ari n g  st a n d ar d   A  D T t o  hi g h -d os e  bi c al ut a  mi d e  ( a  n o n -c astr ati n g   A  R  a nt a g o nist), t h e   m e n 
r a n d o  mi z e d t o t h e   A  D T tr e at  m e nt  ar  m  h a d  a   m e a n  d e cli n e  fr o  m  b as eli n e i n l u  m b ar  s pi n e  b o n e 
mi n er al  d e nsit y   of  2. 5  %  aft er  1 2    m o nt hs  of  t h er a p y  [ 1 8]. R e d u cti o ns  i n  b o n e    mi n er al  d e nsit y 
wit h    A  D T   ar e   cli ni c all y   r el e v a nt  -   pri or   o bs er v ati o n al   st u di es   h a v e   als o   d e  m o nstr at e d   a n 
i n cr e as e d ris k  of  ost e o p or oti c fr a ct ur es   wit h  a n dr o g e n  d e pri v ati o n t h er a p y [ 1 9]. 
1. 3. 4  Q u alit y  of   Lif e   a n d  Ps y c h os o ci al I  m p a ct  of   A n d r o g e n   D e p ri v ati o n  
A n dr o g e n  d e pri v ati o n t h er a p y is  ass o ci at e d   wit h  a n  a d v ers e i  m p a ct  o n  o v er all  q u alit y  of lif e  as 
t y pi c al si d e  eff e cts i n cl u di n g  h ot fl as h es, er e ctil e  d ysf u n cti o n,  f ati g u e,  a n d  d e pr essi o n.  
1. 3. 4. 1   O v e r all   Q u alit y  of   Lif e   Ass ess  m e nt 
A   v ali d at e d   m e as ur e  of  g e n er al  q u alit y  of lif e is t h e  S F - 1 2 Q  O L  s ur v e y  ,  a n  a b br e vi at e d f or  m  of 
t h e  S F-3 6   wit h   w hi c h it is ti g htl y  c orr el at e d  [ 2 0]. I n  a  pri or  pr os p e cti v e  st u d y  of   m e n  u n d er g oi n g 
A  D T,  t h er e    w as  a  st atisti c all y  a n d  cli ni c all y  si g nifi c a nt    m e a n  d e cr e as e  fr o  m  b as eli n e  i n  t h e 
s c or es   of  s e v er al   d o  m ai ns    wit hi n  t h e   S F -3 6   pr ofil e,  i n cl u di n g   g e n er al   h e alt h,   vit alit y,   a n d 
c o  m p osit e  p h ysi c a l h e alt h [ 2 1].   
1. 3. 4. 2   H ot  Fl as h es 
H ot  fl as h es  ar e  a  c o  m  m o n  a  n d   b ot h ers o  m e  s y  m pt o  m  ass o ci at e d    wit h   a n dr o g e n   d e pri v ati o n 
t h er a p y,  t h o u g h  t h e  ex a ct    m e c h a nis  m   r e  m ai ns  u n cl e ar.  Pri or  st u di es  e x a  mi ni n g  t h e  i  m p a ct  of 
A  D T  o n  h ot  fl as h es  h a v e  us e d  a  v ari et y  of  s c al es t o   m e as ur e t h e i n ci d e n c e  a n d  s e v erit y  of  h ot 
fl as h es, i n cl u di n g t h e   H ot  Fl as h  S c or e.   T h e  c urr e nt  st u d y   will  us e t h e   H ot  Fl as h  R el at e d   D ail y 
R el at e d I nt erf er e n c e  S  c al e  (  H F  R  DI S),   w hi c h  h as  pr e vi o usl y  b e e n  v ali d at e d i n  a  st u d y  p o p ul ati o n 
of  br e ast  c a n c er   s ur vi v ors  c o  m p ar e d  t o  a g e -  mat c h e d  c o ntr ols  [ 2 2 ].  I n  t his  st u d y,  t h e   H F  R  DI S 
w as  i nt er n all y  c o nsist e nt,  d e  m o nstr at e d  c orr el ati o ns    wit h  ot h er  h ot  fl as h  v ari a bl es,  c orr el at e d 
wit h   m e as ur es  of  aff e ct  a n d   m o o d,  a n d  d e  m o nstr at e d s e nsiti vit y t o  c h a n g e  o v er ti  m e.  
1. 3. 4 . 3   E r e ctil e a n d   U ri n a r y   D ysf u n cti o n 
Er e ctil e  d ysf u n cti o n is  a   w ell  -c h ar a ct eri z e d  c o  m pli c ati o n  of  a n dr o g e n  d e pri v ati o n t h er a p y,  b ot h 
i n    m e n   wit h  a n d  t h os e   wit h o ut  pri or  r a di c al  pr ost at e ct o  m y  or  r a di ati o n  t h er a p y  t o  t h e  pr ost at e 
gl a n d . E PI  C - 2 6 is  a   w ell-v ali d at e d   m e as ur e  m e nt  of  er e ctil e  a n d  uri n ar y  f u n cti o n   w hi c h  h as  b e e n 
st u di e d  i n  v ari o us  dis e as e  s etti n gs  i n cl u d e d  pri or  pr ost at e  c a n c er  st u di es  a n d    will  b e  us e d  t o 
m e as ur e  er e ctil e f u n cti o n i n t h e  c urr e nt st u d y   [ 2 3].  
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1. 3. 4. 4  F ati g u e 
F ati g u e  is  a  c o  m  m o n  a n d  b ot h ers o  m e si d e  eff e ct  of  a n dr o g e n  d e pri v ati o n t h er a p y   w hi c h  c a n  h a v e 
a n  a d v ers e i  m p a ct  o n  q u alit y  of lif e  f or  s o  m e   m e n  r e c ei vi n g  a n dr o g e n  d e pri v ati o n t h er a p y.  I n  a 
pri or  cr oss -s e cti o n al  st u d y  c o  m p ari n g  5 7    m e n  r e c ei vi n g    A  D T    wit h  5 1  a g e -m at c  h e d  c o ntr ols, 
m or e   m e n i n t h e   A  D T  gr o u p  h a d  s e v er e f ati g u e  c o  m p ar e d t o t h e  c o ntr ol  c o h ort ( 1 4  %  vs.  4  %,  p  =   
0. 0 3) .   T h e   L e e  F ati g u e  s c al e  is  a  w ell  -v ali d at e d   vis u al  a n al o g    m e as ur e  of  f ati g u e,    w hi c h  h as 
d e  m o nstr at e d  hi g h  r eli a bilit y  a n d  v ali dit y  c o  m p ar e d t o t h e  St a nf or d  Sl e e pi n ess  S c al e  [ 2 4]. T h e 
L e e  F ati g u e  S c al e    will  b e  us e d  t o    m e as ur e  t h e  d e gr e e  of  f ati g u e  a n d  c h a n g e  i n  e n er g y  l e v el 
e x p eri e n c e d  b y  p ati e nts r e c ei vi n g   A  D T i n t h e  c urr e nt st u d y.   
1. 3. 4 . 5   D e p r essi o n  
D e pr essi o n is   c o  m  m o n  a n d  fr e q u e ntl y  u n d er di a g n os e d  a  m o n g   m e n  r e c ei vi n g   A  D T  f or  pr ost at e 
c a n c er.  Pri or  st u di es i n di c at e  a  r at e  of  d e pr essi o n i n t his  p ati e nt  p o p ul ati o n t h at  f ar  e x c e e ds t h e 
e x p e ct e d  pr e v al e n c e  a  m o n g  a g e -m at c h e d  c o ntr ols.  I n  a  pri or  cr oss  -s e cti o n al  st u d y  of  4 5    m e n 
r e c ei vi n g    A  D T  (  m e di a n  d ur ati o n   of   A  D T    w as    3. 3   y e ars),  t h e   pr e v al e n c e   of   d e pr essi o n  as 
s cr e e n e d  f or  b y t h e  str u ct ur e d  cli ni c al i nt er vi e  w  usi n g t h e   D S  M -I  V  crit eri a   w as  1 2. 8  %,  8 ti  m es 
t h at  of   t h e  n ati o n al  a v er a g e  i n    m e n  [ 2 5].  I n  t h e  c urr e nt  st u d y,  t h e  P  H  Q - 9,  a    w ell -v ali d at e d 
s cr e e ni n g    m etri c  f or  d e pr essi o n  c o nsisti n g  of  9   it e  ms,    will  b e  us e d  t o    m e as ur e  t h e  c h a n g e  i n 
d e pr essi v e  s y  m pt o  ms  a  m o n g   m e n  b ei n g tr e at e d   wit h  a n dr o g e n  d e pri v ati o n t h er a p y  f or  h or  m o n e 
s e nsiti v e   pr ost at e  c a n c er.   P  H  Q -9  r es ults   m ust    b e  r e vi e  w e d   b y  tr e ati n g   h e a lt h-c ar e   pr o vi d er 
d uri n g t h e  c o urs e  of  p ati e nt’s st u d y  visit.  
1. 3. 4. 6   C o g niti v e  F u n cti o n  
T h er e  is    mi x e d  e vi d e n c e  r e g ar di n g  t h e  i  m p a ct  of  a n dr o g e n  d e pri v ati o n  t h er a p y  o n  c o g niti o n. 
S e v er al  st u di es  h a v e  d e  m o nstr at e d  d e cr e  m e nts i n  ps y c h o  m ot or  s p e e d/ pr o c essi n g  s p e e d, r e a cti o n 
ti  m es,  a n d    w or ki n g    m e  m or y.    V er b al    m e  m or y  a n d  fl u e n c y  h a v e  s h o  w n    m or e    mi x e d  eff e cts  i n 
pri or  st u di es.  T h e   Att e nti o n al  F u n cti o n I n d e x is  a   w ell -v ali d at e d   m etri c  of   w or ki n g   m e  m or y  a n d 
pr o c essi n g  s p e e d  t h at   w as  c h os e n  f or  t h e  c urr e nt  st u d y  t o  b ett er  c a pt ur e  t h e  s p e cifi c  c o g niti v e 
as p e cts  p ot e nti all y  aff e ct e d  b y   A  D T.   
1. 3. 5  R ati o n al e f o r t h e   C o r r el ati v e  St u d y   E n d p oi nts   
1. 3. 5. 1:   G e r  mli n e  P ol y  m o r p his  ms 
I n  c o ntr ast t o   m e as uri n g t h e  ass o ci ati o n  b et  w e e n  effi c a c y  of   A  D T  a n d  g er  mli n e  p ol y  m or p his  ms, 
t he   ass o ci ati o n   b et  w e e n   A  D T  t o xi cit y   a n d    g er  mli n e   v ari ati o n  i n   g e n es   e n c o di n g   pr ot ei ns 
i n v ol v e d  i n   st er oi d   bi os y nt h esis   or   dr u g    m et a b olis  m  is  l ar g el y   u n e x pl or e d.  I n    m et ast ati c 
h or  m o n e- r e c e pt or  p ositi v e  br e ast  c a n c er,  c ert ai n  p ol y  m or p his  ms    wit hi n  t h e  estr o g e n   r e c e pt or 
g e n e  w er e  ass o ci at e d   wit h i n cr e as e d i n ci d e n c e  of  h ot  fl as h es i n  p ati e nts tr e at e d   wit h   t a  m o xif e n 
[ 2 6]. 
 
Wit h  r es p e ct  t o  pri  m ar y  a n dr o g e n  d e pri v ati o n  t h er a p y    wit h   L  H  R  H   a g o nists,  t h er e  h a v e  b e e n 
s e v er al   st u di es  i n v esti g ati n g  t h e   ass o ci ati o n   of   S  N Ps  i n   g e n es   b el o n gi n g  t o  t h e   a n dr o g e n 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
s y nt h esis  p at h  w a y  a n d  dis e as e  o ut c o  m e.  I n  a  pri or  st u d y  i n v esti g ati n g  t h e  ass o ci ati o n  b et  w e e n 
g e n ot y p es  fr o  m  1 2 7  S  N Ps  i n  2 0  diff er e nt  g e n es    wit hi n  t h e  a n dr o g e n  s y nt h eti c  p at h  w a y    wit h 
dis e as e  o ut c o  m es i n   m e n tr e at e d   wit h   A D T f or  a d v a n c e d  pr ost at e  c a n c er, t hr e e  p ol y  m or p his  ms i n 
s e p ar at e  g e n es  (  C  Y P 1 9  A 1,   H S  D 3  B 1,  a n d   H S  D 1 7  B 4)   w er e  ass o ci at e d   wit h ti  m e t o  pr o gr essi o n 
o n     m ulti v ari at e   a n al ysis    [ 2 7].     L ess   is   k n o  w n,   h o  w e v er,   a b o ut   t h e   ass o ci ati o n   b et  w e e n 
p ol y  m or p his  ms   wit hi n  c a n di d a t e  g e n es t h at   mi g ht  pr e di ct  f or  s o  m e  of t h e  p ot e nti al t o xi citi es  of 
A  D T,  i n cl u di n g  t h e    m et a b oli c  t o xi citi es  dis c uss e d  a b o v e.  Pr e di cti n g  p ot e nti al  t o xi cit y  of   A  D T 
m a y  b e  ulti  m at el y  us e d t o  g ui d e  cli ni ci a ns i n  a  v ari et y  of  cli ni c al  s c e n ari os, i n cl u di n g ti  mi n  g  of 
i niti ati o n  of   A  D T i n   m e n   wit h  bi o c h e  mi c all y r el a ps e d  dis e as e. 
 
T h e  c urr e nt  st u d y  s a  m pl e  si z e    will  p er  mit  o nl y  a n  e x pl or at or y  a n al ysis  of  t h e  ass o ci ati o ns 
b et  w e e n  f u n cti o n al,  n o n -s y n o n y  m o us  g er  mli n e  p ol y  m or p his  ms  a n d  t h e    m et a b oli c  t o xi cit y  of 
A  D T.   T h e   h y p ot h esis is t h at  p ol y  m or p his  ms  of f u n cti o n al r el e v a n c e   w hi c h  d e pl et e i ntr a -c ell ul ar 
a n dr o g e ns    m a y  b e  ass o ci at e d    wit h  a n   i n cr e as e d  li k eli h o o d  of    m et a b oli c  t o xi citi es  r el at e d  t o 
a n dr o g e n  d e pri v ati o n t h er a p y, i n cl u di n g i n cr e asi n g ris k  of i ns uli n r esist a n c e.  
 
1. 3. 5. 2   T r a b e c ul a r   B o n e   Mi c r o- A r c hit e ct u r e   
C h a n g es   i n   B  M  D,  es p e ci all y t h os e   m e as ur e d  usi n g   D  X  A  d o  n ot r efl e ct t h e  c h a n g es t a ki n g  pl a c e 
i n t h e  c orti c al  a n d tr a b e c ul ar  b o n e  c o  m p art  m e nts  a n d  d o  n ot  e ntir el y  e x pl ai n  b o n e  str e n gt h  a n d 
fr a ct ur e  ris k.    W e  h a v e  r e c e ntl y  s h o  w n,  usi n g  hi g h-r es ol uti o n  p eri p h er al  c o  m p ut e d  t o  m o gr a p h y 
(  H  R p  Q  C T), t h at  a g e  a n d   m et a b olis  m  r el at e d  c h a n g es i n t h es e  c o  m p art  m e nts  diff er  a n d  r e gi o n al 
c h a n g es  i n    mi cr o -ar c hit e ct ur e  h a v e  pr of o u n d  i  m p a ct  o n  bi o  m e c h a ni c al  c h ar a ct eristi cs  of  b o n e. 
M a  g n eti c  r es o n a n c e i  m a gi n g   m a y b e  us e d t o  q u a ntif yf att y i nfiltr at i o n  i n    m us cl e  o r  s a r c o p e ni a 
t h us   m a y b e  a  p ot e nti al  s urr o g at e f or  ass essi n g l oss  of  str e n gt h. I n  a  p ri o r  st u d y  of  2 6   m e n   wit h 
m et ast ati c  pr ost at e  c a n c er  o n   A  D T t h e l oss i n t h e  c orti  c al  b o n e  c o  m p art  m e nt  is  gr e at er  t h a n  i n 
tr a b e c ul ar   b o n e,   a n d  t h at  t h e  l oss  i n  tr a b e c ul ar   b o n e  is  r es p o nsi bl e  f or  t r a b e c ul a r   b o n e 
d e c r e as es .    T h es e   diff er e nti al  eff e cts  i n  c orti c al  a n d  tr a b e c ul ar   b o n e,  a n d  l oss   of  tr a b e c ul ar 
n u  m b er  h as  pr of o u n d  eff e cts  o n  b o n e str e n g t h.  F urt h er  m or e, t h e  diff er e n c es  b et  w e e n  b o n e l oss i n 
m e n   wit h   m et ast ati c  dis e as e   m a y  b e  diff er e nt t h a n t h os e  o n  pri  m ar y  pr ost at e  c a n c er  a n d  at t h e 
i niti ati o n  of   A  D T t h er a p y.  T h us,   w e f e el  a  gr o u p  of   m e n   wit h  pri  m ar y  pr ost at e  c a n c er  st arti n g  o n 
A  D T    w o ul d  s  er v e  as  a  b ett er    m o d el  f or    m al e  ost e o p or osis,  a n d  assist  i n  d es cri bi n g  t h e  ti  m e -
c o urs e  of    m al e  h or  m o n e  d efi ci e nt  o ns et  of  ost e o p or osis.  Hi g h  -r es ol uti o n  p eri p h er al  c o  m p ut e d 
t o  m o gr a p h y is  a l o  w  d os e t e c h ni q u e t h at  pr o vi d es i  m a g es  d e pi cti n g  c orti c al  a n d tr a b e c ul ar  b o n e 
str u ct ur e. 
 
R e gi o n al   v ari ati o n  i n  tr a b e c ul ar   str u ct ur e   a cr oss   a xi al   s e cti o ns  is   oft e n   o bs c ur e d   b y  t h e 
c o n v e nti o n al  gl o b al  a n al ysis,   w hi c h t a k es  a n  a v er a g e  v al u e f or t h e  e ntir e  c o  m p art  m e nt.   W e  h a v e 
c h ar a ct eri z e d  s p ati al  v ari a bilit y i n  tr a b e c ul ar str u ct ur e   wit hi n  a  cr oss -s e cti o n  at t h e  dist al  r a di us 
a n d  ti bi a,  a n d   g e n d er   a n d  a g e   eff e cts   usi n g  i n   vi v o   hi g h -r es ol uti o n   p eri p h er al   q u a ntit ati v e 
c o  m p ut e d t o  m o gr a p h y (  H  R -p  Q  C T) i n  1 4 6  h e alt h y i n di vi d u als  a g e d  2 0 -7 8  y e ars.  Tr a b e c ul ar  b o n e 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
v ol u  m e   fr a cti o n   (  B  V/ T  V),    n u  m b er   ( T b.  N),   t hi c k n ess   ( T b. T h),   s e p ar ati o n   ( T b. S p),   a n d 
h et er o g e n eit y   ( T b. 1/  N. S  D)     w er e   o bt ai n e d   i n   a   t ot al   of   1 1   r e gi o ns -t h e   e ntir e   tr a b e c ul ar 
c o  m p art  m e nt (t h e  gl o b al   m e a ns), i n n er,  o ut er,  a n d  ei g ht  d efi n e d  s u br e gi o ns.   R e gi o n al  v ari ati o ns 
w er e  e x a  m  i n e d   wit h  r es p e ct t o t h e  gl o b al   m e a ns,  a n d  c o  m p ar e d  b et  w e e n   w o  m e n  a n d   m e n,  a n d 
b et  w e e n  y o u n g  ( 2 0 -2 9  y e ars  ol d)  a n d  el d erl y  ( 6 5 -7 9  y e ars  ol d)  a d ults.   S u bst a nti al  r e gi o n al 
v ari ati o ns i n tr a b e c ul ar  b o n e  str u ct ur e  at t h e  dist al  r a di us  a n d  ti bi a   w er e  r e v e al e d  ( e. g.   B  V/ T  V 
v ari e d  -4 0  % t o  + 5 7  %  a n d  -5 9  % t o  + 1 0 0  %  of t h e  gl o b al   m e a ns, r es p e cti v el y, f or  el d erl y   w o  m e n). 
T h e  i n n er -l at er al  (I L)   s u br e gi o n   h a d  l o  w    B  V/ T  V,    T b.  N,   a n d    T b. T h,   a n d  l o  w    T b. S p   a n d 
T b. 1/  N. S  D  at  b ot h  sit es; t h e  o p p osit e   w as tr u e i n t h e  o ut er -a nt eri or  (  O  A)  s u br e gi o n  at t h e  dist al 
r a di us  a n d  t h e  o ut er-m e di al  (  O  M)  a n d   -p ost eri or  (  O P)  s u br e gi o ns  at  t h e  dist al  ti bi a.    G e n d er 
diff er e n c es    w er e    m ost  pr o n o u n c e d  i n  t h e  i n n er -a nt eri or  (I  A)  s u br e gi o n  c o  m p ar e d  t o  t h e  ot h er 
r e gi o ns  or t h e  gl o b al   m e a n  diff er e n c es  at  bot h  sit es.  Tr a b e c ul ar  str u ct ur e  ass o ci at e d   wit h  a g e  a n d 
diff er e d  b et  w e e n  y o u n g  a n d  el d erl y  a d ults  pr e d o  mi n a ntl y i n t h e i n n er -p ost eri or (I P)  s u br e gi o n  at 
t h e  dist al r a di us  a n d i n t h e I L  a n d I  A  s u br e gi o ns  at t h e  dist al ti bi a;  o n t h e  ot h er  h a n d, it r e  m ai n e d 
u n c h a n g e d i n t h e   O  A s u br e gi o n  at t h e  dist al r a di us  a n d i n t h e   O  M s u br e gi o n  at t h e  dist al ti bi a f or 
b ot h    w o  m e n  a n d    m e n.    W e  d e  m o nstr at e d  t h at  n ot  o nl y  t h e  c o n v e nti o n al  gl o b al  a n al ysis  c a n 
o bs c ur e  r e gi o n al  diff er e n c es,  b ut  als o  ass u  mi n g  b o n e  st at us  fr o  m t h at  o f  s  m all er  s u br e gi o n   m a y 
i ntr o d u c e  a  c o nf o u n di n g  s a  m pli n g  err or.   T h er ef or e,  a  c o  m bi n e d  a p pr o a c h  of  i n v esti g ati n g  t h e 
e ntir e   r e gi o n,   e a c h   s u br e gi o n,   a n d   t h e   c orti c al   c o  m p art  m e nt     m a y   off er     m or e   c o  m pl et e 
i nf or  m ati o n. 
 
1. 3. 5. 3  S e c o n d   Di git:  F o u rt h   Di git   L e n gt h   R ati o  a n d  F et al   T est ost e r o n e   E x p os u r e  
T h e r ati o  b et  w e e n t h e l e n gt h  of t h e  2 n d  a n d  4t h  di gits, t y pi c all y   m e as ur e d  o n t h e ri g ht  h a n d, is  a 
p h ysi c al  tr ait  t h at  c orr el at es    wit h  f et al  t est ost er o n e  e x p os ur e.    T h e  fi n di n g  c a n  b e    m e as ur e d 
t hr o u g h o ut  lif e   a n d   c orr elat es    wit h   p h ysi c al    m a nif est ati o ns   a n d   dis e as e   pr o c ess es  t h at   ar e 
ass o ci at e d   wit h  a n dr o g e n  e x c ess es  s u c h  as  a utis  m,   m y o c ar di al i nf ar cti o n  a n d  pr ost at e  c a n c er.  It 
h as  als o  b e e n  ass o ci at e d    wit h  b e h a vi or al  tr aits  t h at  ar e  c o  m  m o nl y  ass o ci at e d    wit h  a n dr o g e n 
e x c e ss, s u c h  as ris k t a ki n g. 
 
Alt h o u g h t h e li n k  b et  w e e n  2 d: 4 d r ati o  a n d  pr ost at e  c a n c er  h as  b e e n  est a blis h e d i n  o n e st u d y 
p ati e nt   wit h  a  p ositi v e   2 d: 4 d r ati o (i n d e x fi n g er l o n g er t h a n t h e ri n g fi n g er  o n t h e ri g ht  h a n d)  h a d 
a  3 3  % r e d u c e d ris k  of  pr ost at e  c a n c er . 
 
Gi v e n   t h at it is  a   m ar k er  of  br ai n ‘ pri  mi n g’  b y t est ost er o n e,   w e  h y p ot h esi z e t h at  p ati e nts   wit h  a 
hi g h er  2 d: 4 d r ati o ( gr e at er t est ost er o n e  e x p os ur e i n  ut er o)   will  b e   m or e s e nsiti v e t o  c h a n g es i n 
s er u  m t est ost er o n e  at  a n y  p oi nt i n lif e  a n d t h er ef or e   will  e x p eri e n c e  a  gr e at er  d e gr e e  of t y pi c al 
a n dr o g e n  d e pri v ati o n t o xi citi es ( h ot fl us h es,  d e cr e as e d  q u alit y  of lif e,   m o o d s  wi n gs  et c.) t h a n 
t h os e   wit h  a l o  w er r ati o. 
 
T h e r ati o is   m e as ur e d  o n t h e ri g ht  h a n d  a n d  c a n  b e  p erf or  m e d  at  a n y  p oi nt i n st u d y  e ntr y. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   1 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
2.   H y p ot h e si s  a n d  St u d y   O bj e cti v e s  
 
2. 1    H y p ot h esis 
T h e  pri  m ar y  h y p ot h esis  of t h e  st u d y is  t h at  a cti v e  p arti ci p ati o n i n  a   m ulti-dis ci pli n ar y  cli ni c   wit h 
i n di vi d u ali z e d  c o u ns eli n g r e g ar di n g  e x er cis e  a n d  di et ar y  h a bits,  as  c o  m p ar e d t o st a n d ar d- of-c ar e 
wit h  p h ysi ci a n  c o u ns eli n g  d uri n g  t h e  fr a  m e  w or k  of  f oll o  w  -u p  visits,    will  l e a d  t o  di  mi nis h e d 
i  m p a ct  of  a n dr o g e n  d e pri v ati o n  t h er a p y  usi n g  o bj e cti v e    m e as ur es  a n d  s urr o g at e    m ar k ers  of 
i ns uli n  r esist a n c e  a n d  c ar di o v as c ul ar  dis e as e  ris k  f a ct ors,  i n cl u di n g  g ai ns  i n  b o d y  f at    m ass, 
f asti n g   i ns uli n/ gl u c os e   l e v els,    w ei g ht   g ai n   a  m o n g     m e n    wit h   pr ost at e   c a n c er.     W e   f urt h er 
h y p ot h esi z e  t h at  i n di vi d u ali z e d   e d u c ati o n al  s essi o ns   a n d   c o u ns eli n g  r e g ar di n g   ps y c h os o ci al 
as p e cts  of  a n dr o g e n  d e pri v ati o n  will l e a d   t o i  m pr o v e d  p ati e nt  u n d erst a n di n g  a n d  s atisf a cti o n  a n d 
o v er all l ess  a d v ers e i  m p a ct  o n  q u alit y  of lif e  usi n g  v ali d at e d  p ati e nt -r e p ort e d   m etri cs  a d dr essi n g 
t h e  s p e cifi c iss u es  r ais e d   wit h  a n dr o g e n  d e pri v ati o n t h er a p y.  S h o ul d t h e  st u d y  r es ults  fr o  m t his 
pr eli mi n ar y  p h as e  2  st u d y  pr o vi d e  e vi d e n c e  s u p p orti n g  p arti ci p ati o n  i n t h e   S T  A  N  D  cli ni c, t his 
will   pr o vi d e    t h e  j ustifi c ati o n   f or  a   c o nfir  m at or y   r a n d o  mi z e d   cli ni c al  tri al   a cr oss    m ulti pl e 
i n v esti g ati o n al  sit es  t o  ass ess  t h e  g e n er ali z a bilit y  a n d  r e pr o d u ci bilit y  of  t h e    m ulti- dis ci pli n ar y 
cli ni c,  a n d  t o  ass ess  l o n g -t er  m  i  m p a ct  of m ulti  -dis ci pli n ar y  cli ni c  p arti ci p ati o n  o n  i n ci d e n c e  of 
di a b et es,   c ar di o v as c ul ar   dis e as e,   a n d   n o n -pr ost at e   c a n c er   r el at e d     m ort alit y.        Ulti  m at el y, 
e nr oll  m e nt i nt o  a   m ulti -dis ci pli n ar y  cli ni c  f or   m e n r e c ei vi n g   A  D T   m a y  b e c o  m e  a r o uti n e  as p e ct 
of  pr ost at e  c a n c er    m a n a g e  m e nt  as  a    m e a ns  t o    miti g at e  t h e  p ot e nti al l y  si g nifi c a nt  t o xi cit y  of 
a n dr o g e n  d e pri v ati o n t h er a p y.  
 
2 . 2  St u d y   O bj e cti v es 
2. 2 . 1 P ri  m a r y   O bj e cti v e  
R a n d o  mi z e d  c o h o rt:   T o  c o  m p ar e  t h e    m e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e  t o  1 2    m o nt hs  i n 
p er c e nt a g e   b o d y  f at    m ass  a  m o n g    m e n    wit h   pr ost at e  c a n c er  r e c ei vi n g  a n dr o g e n   d e pri v ati o n 
t h er a p y r a n d o  mi z e d t o  p arti ci p at e i n t h e  “ S T  A  N  D ”  cli ni c  vs.  us u al st a n d ar d  of  c ar e. 
 
N o n  -r a n d o  mi z e d  pil ot  c o h o rt:   T o  d et er  mi n e  t h e  f e asi bilit y  of  c o  m pl eti n g    m ulti -dis ci pli n ar y 
S T  A  N  D  cli ni c  visits   wit hi n  c o nt e xt  of  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y f or  pr ost at e  c a n c er. 
 
2. 2. 2  S e c o n d a r y   O bj e cti v es  
 
T o  c o  m p a r e  t h e   m e a n   p e r c e nt   c h a n g e  f r o  m  b as eli n e  t o  1 2   m o nt hs  a n d  p att e r ns  of  c h a n g e 
o v e r ti  m e  d u ri n g  p a rti ci p ati o n i n t h e  S  T  A  N  D  cli ni c  vs.  us u al  st a n d a r d  of  c a r e   wit h  r es p e ct 
t o: 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
M et a b oli c I  m p a ct  o n   Di a b et es  a n d   C ar di o v as c ul ar  Ris k  F a ct ors:    
-   F asti n g  bl o o d  gl u c os e 
-   F asti n g  pl as  m a i ns uli n l e v el  
-   I ns uli n r esist a n c e  as  c al c ul at e d b y   H  O  M  A -I R 
-   H e  m o gl o bi n   A 1 c 
-   F asti n g li pi ds (t ot al  c h ol est er ol,  L  D L,   H  D L, tri gl y c er ci d es)  
-   W aist  cir c u  mf er e n c e   
-   B o d y   w ei g ht/ b o d y   m ass i n d e x 
-   E x er cis e  p att er ns  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e  a n d  a  m b ul at or y  a c c el er o  m et er 
ass ess  m e nt  (s e e   A p p e n di c es  2  a n d  5 r es p e cti v el y) 
-   Bl o o d  pr ess ur e 
 
B o n e   H e alt h:   
-   B o n e  d e nsit y  as  ass ess e d  b y   D  X  A s c a n   
-   2 5- (  O  H)  vit a  mi n   D s er u  m l e v els 
 
Q u alit y  of  Lif e/ Ps y c h os o ci al I  m p a ct:   
-   D e pr essi o n  as   m e as ur e d  b y  P  H  Q  - 9 
-   C o g niti v e f u n cti o n  as   m e as ur e d  b y t h e   Att e nti o n al   F u n cti o n al I n d e x  
-   O v er all  q u alit y  of lif e  as   m e as ur e d  b y  S F  - 1 2 
-   F ati g u e  as   m e as ur e d  b y t h e  L e e  F ati g u e  S c al e  
-   Er e ctil e   a n d  uri n ar y f u n cti o n  as   m e as ur e d  b y E PI  C - 2 6 
-   H ot fl as h s e v erit y  as   m e as ur e d  b y   H ot  Fl as h   R el at e d   D ail y I nt erf er e n c e  S c al e   
 
A  m o n g   m e n  r a n d o  mi  z e d t o  r e c ei v e  us u al  st a n d a r d  of  c a r e t h at  c r oss -o v e r t o  p a rti ci p at e i n 
t h e  S  T  A  N  D  cli ni c  aft e r   m o nt h  1 2  of t h e st u d y: 
 
T o   m e as ur e t h e   m e a n  c h a n g e fr o  m  b as eli n e  at  st art  of  p arti ci p ati o n i n t h e  S T  A  N  D  cli ni c  aft er  1 2 
m o nt hs  of  p arti ci p ati o n i n:  
 
-   M et a b oli c  p  ar a  m et ers i n cl u di n g  p er c e nt a g e  b o d y f at, f asti n g i ns uli n/ gl u c os e,   H  O  M  A -I R, 
b o d y   w ei g ht/ b o d y   m ass i n d e x,   w aist  cir c u  mf er e n c e 
-   B o n e  h e alt h 
-   Q u alit y  of lif e   
-   P ati e nt s atisf a cti o n  
 
A  m o n g   m e n i n t h e  n o n  - r a n d o  mi z e d  pil ot  c o h o rt: 
-   T o   d et er  mi n e  t h e    m e a n   c h a n g e  fr o  m   b as eli n e  t o   1 2    m o nt hs   d uri n g   S T  A  N  D   cli ni c 
p arti ci p ati o n i n t h e  pri  m ar y  a n d  s e c o n d ar y   m et a b oli c  a n d  q u alit y  of lif e  p ar a  m et ers list e d 
a b o v e. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
2. 2. 3   C o r r el ati v e  St u d y   O bj e cti v e s 
•    T o i n v esti g at e  f or  a  r el ati o ns hi p  b et  w e e n i n h erit e d  g e n eti c  p ol y  m or p his  ms  of  f u n c  ti o n al 
r el e v a n c e  n e ar  or   wit hi n  g e n es  e n c o di n g  pr ot ei ns   wit h r ol es i n  st er oi d  h or  m o n e tr a ns p ort 
a n d   a n dr o g e n  r e c e pt or  si g n ali n g    wit h   c h a n g es  i n    m et a b oli c   p ar a  m et ers   a  m o n g    m e n 
tr e at e d   wit h  a n dr o g e n  d e pri v ati o n t h er a p y. 
•    T o  i n v esti g at e   c h a n g es  i n  tr a b e c ul ar   b o n e    mi cr o -ar c hit e ct ur e   as    m e as ur e d   b y    Hi g h 
R es ol uti o n   P eri p h er al    Q  C T  I  m a gi n g  of  r a di us  a n d  ti bi a  d uri n g  a n dr o g e n  d e pri v ati o n 
t h er a p y. 
•    T o i n v esti g at e f or r el ati o ns hi p  b et  w e e n  2 n d di git t o  4 t h di git l e n gt h r ati o ( 2  D: 4  D r ati o)  a n d 
q u alit y  of lif e  o n  a n dr o g e n  d e pri v ati o n t h er a p y. 
•    T o  i n v esti g at e  f or  a  r el ati o ns hi p  b et  w e e n  2 n d di git  t o  4 t h di git  l e n gt h  r ati o  a n d  b as eli n e 
e  m p at h y s c or e  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e . 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
3.  St u d y   D e si g n   
3 . 1   O v e r all  St u d y C h a r a ct e risti cs 
R a n d o  mi z e d,   p h as e   2   st u d y    wit h   cr oss  -o v er   d esi g n  t o   ass ess  t h e  l o n git u di n al  i  m p a ct   of 
p arti ci p ati o n  i n  t h e    m ulti -dis ci pli n ar y  S T  A  N  D  cli ni c   vs.  r e c ei pt  of  us u al  st a n d ar d  of  c ar e   o n 
c h a n g es  i n   k e y    m et a b oli c   p ar a  m et ers,   q u alit y   of  lif e,   a n d   p ati e nt  s atisf a cti o n   a  m o n g    m e n 
r e c ei vi n g  a n dr o g e n  d e priv ati o n t h er a p y f or  pr ost at e  c a n c er.  St a n d ar d -of -c ar e t h er a p y   will  c o nsist 
of  e v er y  3- m o nt h  visits  c o  m pris e d  of r e vi e  w  of   m e di c al  hist or y, t o xi cit y  ass ess  m e nt,  a n d lif est yl e 
m o difi c ati o n  c o u ns eli n g  pr o vi d e d  b y i n di vi d u al  h e alt h  c ar e  pr o vi d er,  L  H  R  H  a n al o g   i nj e cti o ns  b y 
tr ai n e d  o n c ol o g y  n urs e.  P ati e nts i n t h e  us u al  c ar e tr e at  m e nt  ar  m will  h a v e   u nr estri ct e d  a c c ess t o 
e x er cis e,   n utriti o n,   a n d   s y  m pt o  m    m a n a g e  m e nt   s er vi c e   u p o n   p ati e nt  r e q u est   or   as   d e e  m e d 
n e c ess ar y  b y  h e alt h  c ar e  pr o vi d er.  M e n  r a n d o  mi z e d  t o  p arti  ci p ati o n  i n  t h e  S T  A  N  D  cli ni c   will 
h a v e  e v er y  3   m o nt h  visits   wit h  h e alt h  c ar e  pr o vi d ers  a n d  L  H  R  H  a n al o g i nj e cti o ns,   m o nt hl y  s elf -
dir e ct e d  e d u c ati o n al  “  m o d ul es ”  c o v eri n g t h e  v ari o us  as p e cts  of  h or  m o n e t h er a p y  as   w ell  as  e v er y 
3- m o nt h   i n di vi d u ali z e d   c o u ns eli n  g   pr o vi d e d   b y   r e gist er e d   di etiti a n,   e x er cis e   tr ai n er,   a n d 
s y  m pt o  m   m a n a g e  m e nt  s er vi c e .   At t h e  e n d  of  1 2   m o nt hs  of  st u d y  p arti ci p ati o n,  p ati e nts i niti all y 
r a n d o  mi z e d t o r e c ei v e st a n d ar d-of -c ar e,   will  h a v e t h e  o pti o n  of  cr ossi n g -o v er t o  p arti ci p at e i n t h e 
S T  A N  D  cli ni c f or t h e  e ns ui n g  1 2   m o nt hs.  
 
A  n o n  -r a n d o  mi z e d  pil ot  c o h ort  of  p ati e nts r e c ei vi n g  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y   will  b e 
e nr oll e d  i n   p ar all el  t o   ass ess  t h e  f e asi bilit y   of   S T  A  N  D   cli ni c   p arti ci p ati o n  i n  t his   p ati e nt 
p o p ul ati o n. 
 
3. 2  St u d y   E n d p oi nt s 
3. 2. 1  P ri  m a r y   E n d p oi nt  
R a n d o  mi z e d  c o h o rt:   M e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e t o  1 2   m o nt hs i n  p er c e nt a g e  b o d y  f at 
m ass  as   m e as ur e d  b y  bi o el e ctri c al i  m p e d a n c e  a n al y z er   (s e e   A p p e n di x  4).  
N o n  -r a n d o  mi z e d   c h e  m o h o r  m o n al   c o h o rt:   P er c e nt a g e   of   c o  m pl et e d   S T  A  N  D   cli ni c   visits 
d uri n g t h e  c o urs e  of t h e  1 2   m o nt h  S T  A  N  D  cli ni c  p arti ci p ati o n. 
3. 2. 2  S e c o n d a r y   E n d p oi nts  
M e a n  p er c e nt  c h a n g e fr o  m  b as eli n e t o  1 2   m o nt hs  a n d  p att er ns  of  c h a n g e fr o  m  b as eli n e   wit h 
r es p e ct t o t h e f oll o  wi n g: 
M et a b oli c I  m p a ct  o n   Di a b et es  a n d   C ar di o v as c ul ar   Dis e as e  Ris k  F a ct ors:    
-   F asti n g  bl o o d  gl u c os e 
-   F asti n g  pl as  m a i ns uli n l e v el  
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
-   I ns uli n r esist a n c e  as  c al c ul at e d  b y   H  O  M  A-I R 
-   H e  m o gl o bi n   A 1 c 
-   F asti n g li pi ds (t ot al  c h ol est er ol,  L  D L,   H  D L, tri gl y c er ci d es)  
-   W aist  cir c u  mf er e n c e   
-   B o  d y   w ei g ht/ b o d y   m ass i n d e x 
-   E x er cis e  p att er ns  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e  a n d  a  m b ul at or y  a c c el er o  m et er 
ass ess  m e nt  (  A p p e n di c es  2  a n d  5 r es p e cti v el y) 
-   Bl o o d  pr ess ur e 
 
B o n e   H e alt h:   
-   B o n e  d e nsit y  at t h e l u  m b ar s pi n e, f e  m or al  n e c k,  a n d t ot al  hi p  as  ass e  ss e d  b y   D  X  A s c a n 
a  m o n g  p ati e nts   wit h o ut  b o n e   m et ast as es  at t h e ti  m e  of st u d y  e ntr y  
-   S er u  m  2 5- (  O  H)  vit a  mi n   D l e v els 
 
Q u alit y  of  Lif e/ Ps y c h os o ci al I  m p a ct:   
-   D e pr essi o n  as   m e as ur e d  b y  P  H  Q  - 9 
-   C o g niti v e f u n cti o n  as   m e as ur e d  b y   Att e nti o n al  F u n cti o n al I n d e x 
-   O v er all  q u alit y  of lif e  as   m e as ur e d  b y  S F  - 1 2 
-   F ati g u e  as   m e as ur e d  b y t h e  L e e  F ati g u e  S c al e  
-   Er e ctil e  a n d  uri n ar y f u n cti o n  as   m e as ur e d  b y  E PI  C - 2 6 
-   H ot fl as h s e v erit y  as   m e as ur e d  b y   H ot  Fl as h   R el at e d   D ail y I nt erf er e n c e  S c al e   
 
P ati e nt  S atisf a cti o n:   
-   P ati e nt s atisf a cti o n   as   m e as ur e d  b y  a  v ali d at e d  q u esti o n n air e 
-   P ati e nt i nsi g ht  a n d  u n d erst a n di n g  of tr e at  m e nt  a n d  dis e as e- r el at e d iss u es  as   m e as ur e d  b y 
a s elf -a d  mi nist er e d  ass ess  m e nt   
 
3. 2. 3   C o r r el ati v e  St u d y   E n d p oi nt s 
 
•    Ass o ci ati o n  b et  w e e n i n h erit e d  g e n eti c  p ol y  m or p his  ms  of f u  n cti o n al r el e v a n c e  n e ar  or 
wit hi n  g e n es  e n c o di n g  pr ot ei ns   wit h r ol es i n st er oi d  h or  m o n e tr a ns p ort  a n d  a n dr o g e n 
r e c e pt or si g n ali n g   wit h  c h a n g es i n   m et a b oli c  p ar a  m et ers  a  m o n g   m e n tr e at e d   wit h 
a n dr o g e n  d e pri v ati o n t h er a p y. 
•    M e a n  c h a n g e fr o  m  b as eli n e i n tr a b e c ul ar  b o n e  ar c hit e ct ur e  as   m e as ur e d  b y tr a b e c ul ar 
b o n e  n u  m b er ( T b  N)  a n d tr a b e c ul ar  b o n e  v ol u  m e fr a cti o n (  B  V/ T  V)  aft er  1 2   m o nt hs  of 
a n dr o g e n  d e pri v ati o n t h er a p y. 
•    Ass o ci ati o n  b et  w e e n  2  D: 4  D r ati o   wit h  c h a n g e i n  q u alit y  of lif e  o n  a n dr o g e n  d e pri v ati o n 
t h er a p y. 
•    A  ss o ci ati o n  b et  w e e n  2  D: 4  D r ati o   wit h  b as eli n e  e  m p at h y s c or e  as   m e as ur e d  b y  v ali d at e d 
q u esti o n n air e. 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
3. 3  St u d y  S c h e  m a  
 
 
 
3. 3 . 1  P ri  m a r y   C o  m pl eti o n: 
 
St u d y  a c cr u al is  a nti ci p at e d t o  b e  a p pr o xi  m at el y  2  p ati e nts  p er   m o nt h, l e a di n g t o  a n  a c cr u al 
d ur ati o n  of  a p pr o xi  m at el y   4 0 m o nt hs.   A nti ci p at e d ti  m e fr o  m l ast  p ati e nt  e nr oll e d t o  pri  m ar y 
st u d y  c o  m pl eti o n  a n d  a n al ysis  of  pri  m ar y  a n d s e c o n d ar y  e n d p oi nts  e q u als  a p pr o xi  m at el y  1 2 
m o nt hs, l e a di n g t o t h e  pri  m ar y  c o  m pl eti o n  of st u d y i n  a p pr o xi  m at el y  5 2   m o nt hs   fr o  m first 
p ati e nt  e nr oll e d . 
 
St u d y  a c cr u al  of t h e  2 0  p ati e nt  n o n-r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort   will  b e  c o  m pl et e d i n 
p ar all el  a n d is  esti  m at e d t o  b e  a p pr o xi  m at el y  0. 8  p ati e nts/  m o nt h, l e a di n g t o  a n  a p pr o xi  m at e  2 4 
p ati e nt  a c cr u al  p eri o d.   
 
3. 3 . 2  St u d y   C o  m pl eti o n: 
 
T h e t ot al st u d y  d ur ati o n i n cl u di n g f oll o  w  u p  is  esti  m at e d t o  b e  5  y e ars.    
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
4.  St u d y  P o p ul ati o n  
 
8 0  e v al u a bl e  p ati e nts   wit h  pr ost at e  c a n c er  wit h  c o n c urr e nt  or  pl a n n e d tr e at  m e nt   wit h  a n dr o g e n 
d e pri v ati o n  t h er a p y    will  b e  eli gi bl e  f or  st u d y  p arti ci p ati o n .  P ati e nts    m ust  h a v e  i niti at e d    A  D T 
wit hi n  6   m o nt hs  pri or t o  d a y  1  of  st u d y  e ntr y,  a n d t h e  e x p e ct e d  d ur ati o n  of   A  D T   m ust  b e  at l e ast 
1 2   m o nt hs fr o  m st u d y  e ntr y.  
 
2 0  p ati e nts   w h o  ar e r e c ei vi n g  or  pl a n ni n g t o r e c ei v e  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y   will  b e 
e nr o ll e d i n  a  p ar all el  n o n-r a n d o  mi z e d  c o h ort, t o  est a blis h t h e  f e asi bilit y  of  c o  m pl eti n g  S T  A  N  D 
cli ni c  visits i n t his  p ati e nt  p o p ul ati o n.  
 
4. 1  I n cl usi o n   C rit e ri a  
•    Hist ol o gi c  c o nfir  m ati o n  of  a d e n o c ar ci n o  m a  of t h e  pr ost at e 
•    R e c ei vi n g  or  pl a n ni n g t o r e c ei v e   A  D T   wit h  L  H  R  H  a g o nist  or  a nt a g o nist  
•    E x p e ct e d  d ur ati o n  of   A  D T  at l e ast  1 2   m o nt hs fr o  m  d at e  of st u d y  c o ns e nt 
•    C o n c urr e nt  a nti a n dr o g e n t h er a p y  all o  w e d  b ut  n ot r e q uir e d 
•    First  d os e  of  L  H  R  H  a g o nist  or  a nt a g o nist  n o   m or e t h a n  6   m o nt hs  pri or t o  d at e  of st u d y 
c o ns e nt 
•    Pri or/ c o n c urr e nt r a di ati o n  all o  w e d 
•    Ot h er i n v esti g ati o n al  a g e nts i n  a d diti o n t o  L  H  R  H  a g o nist/ a nt a g o nist  ar e  all o  w e d ( e. g. 
n o v el  a nti- a n dr o g e ns,  a n dr o g e n s y nt h esis i n hi bit ors) 
•    Pri or  a n dr o g e n  d e pri v ati o n t h er a p y  all o  w e d,  pr o vi d e d t h er e is  d o c u  m e nt e d  e vi d e n c e  of 
t est ost er o n e r e c o v er y t o  >  1 5 0  n g/ d L  a n d  gr e at er t h a n  1 2   m o nt hs  d ur ati o n  b et  w e e n l ast 
“ eff e cti v e ”  d at e  of   A  D T  a n d  d at e  of st u d y  c o ns e nt 
•    R a n d o  mi z e d  c o h o rt  o nl y:   
o    N o  pri or  c h e  m ot h er a p y   wit hi n  1 2   m o nt hs  of st art  d at e  of st u d y 
o    N o  pl a n n e d  c h e  m ot h er a p y  at l e ast  1 2   m o nt hs fr o  m st u d y  e ntr y 
•    N o n  -r a n d o  mi e d  pil ot  c o h o rt:  
o    C o n c urr e nt  c h e  m ot h er a p y   (i niti at e d   wit hi n  3   m o nt hs  of st u d y  e ntr y)  or  pl a n n e d 
c h e  m ot h er a p y   wit hi n  3   m o nt hs  of st u d y  e ntr y 
•    E  C  O  G  p erf or  m a n c e st at us  of  0  –  2  
•    A bili  t y t o si g n   writt e n i nf or  m e d  c o ns e nt 
•    Willi n g t o  att e n d   m o nt hl y  cli ni c  visits  at   U  C S F   
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
4. 2  E x cl usi o n   C rit e ri a   
•    P h ysi c all y  u n a bl e  or  u n  willi n g t o  p arti ci p at e i n r e c o  m  m e n d e d  e x er cis e  pr o gr a  ms  or tr a v el 
t o   U  C S F  o n  a   m o nt hl y  b asis 
•    Pr es e n c e  of  p er  m a n e nt  p a c e  m a k e r  or i  m pl a nt a bl e m e di c al  d e vi c e.    
o    Artifi ci al j oi nt  pr ost h es es  a n d  v e n o us filt ers  ar e  all o  w e d.  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
5 .  St u d y D r u g     
 
5. 1   L u pr o n   D e p ot ( L e u pr oli d e  a c et at e f or  d e p ot s us p e nsi o n)   D es cri pti o n,  F or  m ul at i on  a n d  
St or a g e  
 
5. 1. 1   D es cri pti o n    
 
L u pr o n   D e p ot ( L e u pr oli d e   a c et at e ) is  a s y nt h eti c   n o n a p e pti d e   a n al o g  of  n at ur all y  o c c urri n g  
g o n a d otr o pi n r el e asi n g  h or  m o n e (  G n  R  H  or  L  H- R  H).     
 
5. 1. 2  F or  m ul ati o n  
 
L u pr o n   D e p ot ( L e u pr oli d e  a c et at e ) f or i nj e cti o n is  a st eril e,  a q u e o us s ol uti o n i nt e n d e d f or 
s u b c ut a n e o us i nj e cti o n. It is  a v ail a bl e i n  a  2. 8   m L   m ulti pl e- d os e  vi al  c o nt ai ni n g l e u pr oli d e 
a c et at e ( 5   m g/  m L),  s o di u  m  c hl ori d e,   U S P ( 6. 3   m g/  m L) f or t o ni cit y  a dj ust  m e nt,  b e n z yl  al c o h ol, 
N F  as  a  pr es er v ati v e  ( 9   m g/  m L),  a n d   w at er f or i nj e cti o n,   U S P.  T h e  p  H   m a y  h a v e  b e e n  a dj ust e d 
wit h s o di u  m  h y dr o xi d e,   N F  a n d/ or  a c eti c  a ci d,   N F.  T h e  p  H r a n g e is  4. 0 t o  6. 0.   
 
T h e  vi al is  p a c k a g e d  as  a   4   D a y  P ati e nt   A d  mi nistr ati o n   Kit   wit h  1 4  dis p os a bl e s yri n g es  a n d  2 8 
al c o h ol s  w a bs,   N  D  C  0 1 8 5- 7 4 0 0- 8 5.   
 
5. 1. 3  St or a g e  
 
St or e  b el o  w  7 7° F ( 2 5°  C).   D o  n ot fr e e z e.  Pr ot e ct fr o  m li g ht; st or e  vi al i n  c art o n  u ntil  us e. 
 
G ui d eli n es f or   A d  mi nistr ati o n:   S e e  Tr e at  m e nt  a n d   D os e   M o difi c ati o n s e cti o n  of  pr ot o c ol 
 
5. 2        Eli g ar d   D es cri pti o n,  F or  m ul ati o n,  a n d  St or a g e 
 
5. 2. 1   D es cri pti o n 
 
Eli g ar d is  a st eril e  p ol y  m eri c   m atri x f or  m ul ati o n  of l e u pr oli d e  a c et at e,  a   G n  R  H  a g o nist  . 
 
5. 2. 2  F or  m ul ati o n  
 
Eli g ar d  is  pr efill e d  a n d s u p pli e d i n t  w o s e p ar at e, st eril e s yri n g es   w h os e  c o nt e nts  ar e   mi x e d 
i  m  m e di at el y  pri or t o  a d  mi nistr ati o n.  T h e t  w o s yri n g es  ar e j oin e d  a n d t h e si n gl e  d os e  pr o d u ct is 
mi x e d  u ntil it is  h o  m o g e n o us.  
 
Eli g ar d  is  a d  mi nist er e d s u b c ut a n e o usl y,   w h er e it f or  ms  a s oli d  dr u g  d eli v er y  d e p ot. 
 
5. 2. 3  St or a g e   
 
St or e  at  2  –  8 °  C ( 3 5. 6  –  4 6. 4 ° F) 
 
G ui d eli n es f or   A d  mi nistr ati o n:   S e e  Tr e at  m e nt  a n d   D os e   M o difi c ati o n s e cti o n  of  pr ot o c ol. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
5. 3     Z ol o d e x   D es cri pti o n,  F or  m ul ati o n  a n d  St or a g e 
 
5. 3. 1    D es cri pti o n  
 
Z ol a d e x  ( g os er eli n  a c et at e) is  a s y nt h eti c  d e c a p e pti d e  a n al o g  of  g o n a d otr o pi n r el e asi n g 
h or  m o n e (  G n  R  H  or  L  H  R  H). 
 
5. 3. 2  F or  m ul ati o n  
 
Z ol a d e x  ( g os er eli n  a c et at e)  d e p ot is s u p pli e d  as  a  c yli n dri c al r o d  of  bi o d e gr a d a bl e  a n d 
bi o c o  m p ati bl e   D- L  L a cti d e - gl y c oli d e  c o p ol y  m er.  E a c h  Z  O L  A  D E  X  d e p ot  c o nt ai ns  g os er eli n 
a c et at e  e q ui v al e nt t o  3. 6   m g  of  g os er eli n.  T his  d e p ot is  pr es e nt e d i n  a st eril e r e a d y- t o- us e s yri n g e 
wit h  a  1 6  g a u g e  n e e dl e f or  a si n gl e s u b c ut a n e o us i nj e cti o n.  T his si n gl e-  d os e s yri n g e is  ass e  m bl e d 
wit h  a  pr ot e cti v e sl e e v e ( S af e S yst e  m  ™) i n  a s e al e d, st eril e  p o u c h t h at  c o nt ai ns  a  d esi c c a nt.   
 
5. 3. 3  St or a g e   
 
Pr ot e ct fr o  m li g ht  a n d   m oist ur e.  St or e i n t h e i nt a ct  p a c k a g e  b et  w e e n  2°  C  a n d  2 5°  C. 
 
G ui d eli n es f or   A d  mi nistr ati o n:   S e e  Tr e at  m e nt  a n d   D os e   M o difi c ati o n s e cti o n  of  pr ot o c ol 
 
5. 4     T elst ar  D es cri pti o n,  F or  m ul ati o n,  a n d  St or a g e  
 
5. 4. 1   D es cri pti o n  
 
5. 4. 1  Tr elst ar is  a s y nt h eti c  d e c a p e pti d e   a g o nist  a n al o g u e  of  g o n a d atr o pi n r el e as e  h or  m o n e 
(  G n  R  H). 
 
5. 4. 2  F or  m ul ati o n  
 
Tr elst ar is  a d  mi nist er e d  as  a si n gl e i ntr a  m us c ul ar i nj e cti o n i n  eit h er  b utt o c k.    T h e l y o p hili z e d 
mi cr o gr a n ul es  ar e t o  b e r e c o nstit ut e d i n st eril e   w at er.    N o  ot h er  dil u e nt s h o ul d  b e  us e d.   D u e t o 
diff er e nt r el e as e  c h ar a ct eristi cs, t h e  d os a g e str e n gt hs  ar e  n ot  a d diti v e  a n d   m ust  b e s el e ct e d  b as e d 
o n t h e  d esir e d  d osi n g s c h e d ul e:  3. 7 5   m g  e v er y  4   w e e ks,  1 1. 2 5  e v er y  1 2   w e e ks  or  2 2. 5   m g  e v er y 
2 4   w e e ks. 
 
5. 4. 3  St or a g e   
 
St or e  at  2 0 - 2 5°  C ( 6 8- 7 7° F).  [ S e e   U S P   C o ntr oll e d   R o o  m  T e  m p er at ur e.]    D o  n ot fr e e z e  Tr elst ar 
wit h   MI  XJ E  C T.   
 
G ui d eli n es f or   A d  mi nistr ati o n:   S e e  Tr e at  m e nt  a n d   D os e   M o difi c ati o n s e cti o n  of  pr ot o c ol 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   2 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
6 . D r u g   T r e at  m e nt  Pl a n  
 
6. 1  L  H  R  H   R o ut e  of   A d  mi nistr ati o n ,  Pri  m ar y  Si d e  Eff e cts,  a n d   D os e   M o difi c ati o ns  a n d   D osi n g 
D el a ys   
 
6. 1. 1    R o ut e  of   A d  mi nistr ati o n  
 
T h e  L  H  R  H a i nj e cti o ns   will  b e  d eli v er e d  eit h er s u b c ut a n e o usl y ( Eli g ar d  ®,  Z ol a d e x  ®)  or 
i ntr a  m us c ul arl y ( L u pr o n   D e p ot  ®  or  Tr elst ar  ®)  b y  a tr ai n e d  h e alt h  c ar e  pr o vi d er   w hil e  o n 
pr ot o c ol t h er a p y. 
 
6. 1. 2  Pri  m ar y  Si d e  Eff e cts  
 
H ot fl as h es,  d e cr e as e d li bi d o,  br e ast  p ai n,  g y n e c o  m asti a,  h y p er gl y c e  mi a,  h y p er c h ol est er ol e  mi a, 
d e cr e as e d  b o n e   mi n er al  d e nsit y, f ati g u e,  a n e  mi a,  m o o d  c h a n g es. 
 
6. 1. 3    Dr u g  S u p pl y 
 
T h e  dr u gs   will  b e  c o  m  m er ci all y s u p pli e d.  
 
F or  a  c o  m pl et e  d es cri pti o n  of t h es e  dr u gs,  pl e as e s e e t h e  p a c k a g e i ns erts. 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
7 .  St u d y   A cti viti e s 
 
7 . 1  St u d y  S c h e d ul e 
 
P r e -St u d y/  
S c r e e ni n g   
(  wit hi n 6 
w e e ks  of 
D a y  1  of 
St u d y)  
D a y   1 
St u d y   Visit  
E n d  of 
E v e r y 
M o nt h    
( +/-  2 w e e k  s) 
E n d  of 
E v e r y  3 
M o nt hs    
( +/- 2   w e e ks)  
E n d  of 
M o nt h  1 2 
St u d y   Visit  
( +/- 2   w e e ks)  
F oll o  w   U p 
Visit l  
(6   m o nt hs 
aft e r 
c o  m pl eti o n 
of  S  T  A  N  D 
cli ni c ) 
P h ysi c al  E x a  m 
wit h   H e alt h   C ar e 
Pr o vi d er  
(  B ot h st u d y  ar  ms) 
X 
X 
 
X 
X 
X 
L  H  R  H   A n al o g u e a 
 
X 
 
X 
 
 
E x er cis e, 
N utriti o n,   
S y  m pt o  m 
M a n a g e  m e nt 
c o u ns eli n g b 
 
X 
X 
 
 
 
E d u c ati o n al 
M o d ul es ( S T  A  N  D 
cli ni c  ar  m  o nl y ) 
 
 
X 
 
X 
 
 
 
C o u ns eli n g, 
r e vi e  w t ests  a n d 
q u esti o n n air es  
 
 
 
X 
X 
X 
I nf or  m e d   C o ns e nt   
X   
 
 
 
 
 
 
R a n d o  mi z ati o n     
X   
 
 
 
 
 
D e  m o gr a p hi cs     
X   
 
 
 
 
 
 
P ast   M e di c al 
Hist or y   
X 
 
 
 
 
 
C o n c o  mit a nt 
M e di c ati o ns
i 
X 
X 
 
X 
X 
 
Q  O L  / e  m p at h y 
Q u esti o n n air es c 
 
X 
 
X 
X 
X 
C o  -m or bi dit y 
Ass ess  m e nt d 
X 
 
 
 
 
 
R ati o  of  2 n d t o  4t h 
di git fi n g er l e n gt h e 
X 
 
 
 
 
 
W ei g ht/  B o d y 
M ass 
I n d e x/ P er c e nt 
B o d y   F at f 
X 
X 
 
X 
X 
X 
E  C  O  G 
P erf or  m a n c e 
 
 
X  
 
X 
X 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
D  X  A   S c a n g  
X 
 
 
 
X 
 
H  R p  Q  C T 
( o pti o n al)h 
X 
 
 
 
X 
 
S er u  m  P S  A i    
X 
X 
 
X 
X 
X 
S er u  m t est ost er o n e    
 
X j 
 
 
X 
X 
S er u  m  2 5 -(  O  H) 
vit a  mi n  D l e v el   
 
X 
 
X 
X 
 
F asti n g 
gl u c o s e/li pi d 
p a n el,   H g b  A 1 c, 
i ns uli n l e v el 
 
X 
 
X 
X 
X 
H e  m o gl o bi n   A 1 c     
 
X 
 
X 
X 
X 
Pl as  m a/s er u  m f or 
b a n ki n g k 
 
X 
 
X 
X 
X 
P  B  M  Cs f or 
g er  mli n e 
p ol y  m or p his  ms  
( o pti o n al)k 
 
X 
 
 
 
 
a.  P ati e nts   w h o  h a v e st art e d   A  D T  pri or t o st u d y  e nr oll  m e nt   will  b e  k e pt  o n s a  m e s c h e d ul e f or  n e xt  d os e  of  L  H  R  H 
a n al o g  a n d  pr o vi d er  visit   w hil e  o n st u d y.   O n st u d y  p ati e nts   will r e c ei v e  L  H  R  H  a g o nist  e v er y  3   m o nt hs  ( +/- 1   w e e k), 
o n s a  m e  d a y  a s  h e alt h  c ar e  pr o vi d er  visits   w h e n e v er  p ossi bl e.   
b :  P ati e nts r a n d o  mi z e d t o t h e  S T  A  N  D  cli ni c will  visit   wit h  o n e  of t hr e e   s p e ci alti es ( e x er cis e,  n utriti o n, s y  m pt o  m 
m a n a g e  m e nt  )  at  e a c h   m o nt hl y  visit.  T h e t ot al  n u  m b er  of  visits   wit h  e a c h s p e ci alt y   will  b e f o ur  o n  a n  e v er y  3-m o nt h 
b asis.  T h e r ot ati o n  of t h e s c h e d ul e  of  pr o vi d ers   m a y  b e  a dj ust e d  d e p e n di n g  u p o n  a v ail a bilit y  of  pr o vi d er  a n d  p ati e nt. 
P ati e nts r a n d o  mi z e d t o t h e  us u al  c ar e st u d y  ar  m   will  b e r ef err e d t o  n utriti o n,  e x er cis e,  a n d s y  m pt o  m   m a n a g e  m e nt 
s er vi c es  u p o n  p ati e nt r e q u est  or  as  d e e  m e d  n e c e ss ar y  b y  h e alt h  c ar e  pr o vi d er.   
c : Q u alit y  of lif e  q u e sti o n n air e s t o  b e  c o  m pl et e d i n cl u d e  S F  -1 2,  E PI  C -2 6 , H ot  Fl as h   R el at e d   D a  il y I nt erf er e n c e 
S c al e ,  L e e  F ati g u e  S c al e, P  H  Q -9,   At t e nti o n al  F u n cti o n al I n d e x,  E x er cis e q u esti o n n air es ,  a n d  e  m p at h y  q u oti e nt- 8 
(s e e   A p p e n di x  2).  T h es e  q u esti o n n air es   m a y  b e  c o  m pl et e d  o nli n e  a h e a d  of s c h e d ul e d  visit  or  at t h e ti  m e  of  cli ni c 
visit,  eit h er  e l e ctr o ni c all y  or  o n  p a p er.  T h e  P  H  Q-9 s c al e   m ust  b e  c o  m pl et e d  o n  p a p er  o n t h e s a  m e  d a y  as  st u d y  visit, 
a n d r e vi e  w e d  a n d si g n e d  b y  h e alt h  c ar e  pr o vi d er  pri or t o  p ati e nt  dis c h ar g e fr o  m  cli ni c.   
d :   Ass ess e d   wit h   C h arls o n   C o  m or bi dit y I n d e x (s e e   A p p e n di x  3) 
e:  M e as ur e d  b y  c ali p er (s e e  S e cti o n  1).  F or  p ati e nts  alr e a d y  e nr oll e d  o n st u d y   w h o  di d  n ot  c o  m pl et e  at  b as eli n e, t his 
m e as ur e  m e nt   will  b e  p erf or  m e d  at t h e  n e xt  pl a n n e d st u d y  visit.   
f: P er c e nt  b o d y f at t o  b e   m e as ur e d  usi n g  bi oi  m p e d a n c e  d e vi c e  o n   C 1  D 1,  e v er y  3  m o nt hs,  a n d  e n d  of   m o nt h  1 2   o n 
st u d y ( s e e   A p p e n di x  4) 
g : B o n e   mi n er al  d e nsit y   m e a s ur e d  at t h e l u  m b ar s pi n e  , t ot al  hi p,  a n d f e  m or al  n e c k ( p erf or  m e d   wit hi n  1 2   w e e ks  of 
d a y  1  of st u d y)  
h:   Hi g h r es ol uti o n  q u a ntit ati v e  p eri p h er al   C T  of t h e r a di us  a n d ti bi a ( o p ti o n al) 
i: B  as eli n e  P S  A  d et er  mi n e d  d uri n g s cr e e ni n g if  n ot  alr e a d y t a ki n g  A  D T   
j:  I n cl u d e s cr e e ni n g  ass ess  m e nt  or s er u  m t est ost er o n e  of  pri or r e c ei pt  of   A  D T  
k:  S e e   A p p e n di x  6 f or  c oll e cti o n  a n d  pr o c essi n g i nstr u cti o ns  
l:   F oll o  wi n g  c o  m pl eti o n  of  S T  A  N  D  cli ni c  p arti ci p ati o n,  p ati e nts   will  b e f oll o  w e d  b y t el e p h o n e  visit  aft er  2  a n d  4 
m o nt hs t o  ass ess  a d h er e n c e t o r e c o  m  m e n d e d  di et/ e x er cis e  pl a ns.   At  6   m o nt hs,  p ati e nts   will r et ur n f or  cli ni c 
ass ess  m e nt . 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
7 . 2 S c r e e ni n g   Visit  (  wit hi n 6  w e e ks  of   D a y  1  of  St u d y)   
S cr e e ni n g  pr o c e d ur es  a n d i nf or  m e d  c o ns e nt  as   w ell  as   writt e n  h e alt h i nf or  m ati o n  a ut h ori z ati o n  
m ust  b e  c o  m pl et e d   wit hi n   6  w e e ks  of  d a y  1  of  st u d y.   All  r es e ar c h  -r el at e d  pr o c e d ur es    will  b e 
c o n d u ct e d  aft er  p ati e nt  h as si g n e d   writt e n  c o ns e nt t o  p arti ci p at e i n t h e st u d y.  
T h es e  pr o c e d ur es i n cl u d e:  
•    P h ysi c al  e x a  m  a n d   m e di c al  hist or y  
•    D e  m o gr a p hi cs  a n d  dis e as e  c h ar a ct eristi cs:   
o    D at e  of  pr ost at e  c a n c er  di a g n osis   
o    Gl e as o n  gr a d e  a n d  P S  A  at t h e ti  m e  of  di a g n osis 
o    T y p e  a n d  d at e  of  pri or l o c al t h er a p y (if  a n y)   
o    D at e   of     A  D T   i ni  ti ati o n   a n d   i n di c ati o n   ( a dj u v a nt,   bi o c h e  mi c al   r el a ps e,   or 
m et ast ati c  dis e as e)   
o    C o n c urr e nt  us e  of  a nti- a n dr o g e n ( y es/ n o) 
o    C o n c urr e nt r a di ati o n t h er a p y ( y es/ n o) 
o    M et ast ati c st at us  at ti  m e  of st u d y  e ntr y ( n o n e,  b o n e  o nl y, s oft tiss u e,  a n y  vis c er al)   
Cli ni c al   Ass e  ss  m e nt  
•    C o  -  m or bi dit y  ass ess  m e nt  b y   C h arls o n   C o-  m or bi dit y  S c al e (  A p p e n di x  3) 
•    Q u alit y  of lif e  q u esti o n n air es (s e e   A p p e n di x  2): 
o    S F -1 2,    E PI C -2 6,    H F  R  DI S,    L e e   F ati g u e   S c al e,   P  H  Q -9,    Att e nti o n al   F u n cti o n al 
I n d e x,  e x er cis e  p att er ns,  e  m p at h y s c al e 
•    C o n c o  m  it a nt   m e di c ati o n  
•    W  ei g ht  a n d b o d y   m ass i n d e x 
•    Ass ess  m e nt  of r ati o  of  2 n d di git t o  4 t h di git fi n g er l e n gt h  usi n g  c ali p er  ass ess  m e nt  
R a di o  g r a p hi c  Ass ess  m e nt   
•    D  X  A   B o n e   D e nsit y  S c a n   ( c o  m pl et e d   wit hi n  1 2   w e e ks  of   D a y  1  of st u d y) 
•    Hi g h r es ol uti o n  p eri p h er al  q u a ntit ati v e   C T s c a n  of t h e  dist al ti bi a  a n d r a di us ( o pti o n al)   
L a b o r at o r y   Ass ess  m e nt 
•    B as eli n e  P S  A   m e as ur e  m e nt    
•    S er u  m t est ost er o n e (if  pri or r e c ei pt  of  a n dr o g e n  d e pri v ati o n t h er a p y) 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
7 . 3   R a n d o  mi z ati o n  
O n c e  eli gi bilit y is  c o nfir  m e d   a n d  p ati e nt  h as  si g n e d i nf or  m e d  c o ns e nt ,  p ati e nts   will  b e  str atifi e d 
a c c or di n g t o  d ur ati o n  of   A  D T  pri or t o  st u d y  e ntr y  ( ≤  3  m o nt hs  vs.   3- 6   m o nt hs)  a n d  b o d y   m ass 
i n d e x  at st u d y  e ntr y ( ≤  3 0  vs.  >  3 0). T h e y   will  b e r a n d o  mi z e d   wit h  e q u al  pr o b a bilit y t o  o n e  of t h e 
t  w o  st u d y  ar  ms  fr o m   wit hi n  e a c h  of   t h e  si x  str at a.    B al a n c e  i n  tr e at  m e nt  assi g n  m e nt    will  b e 
a c hi e v e d  usi n g  a  r a n d o  mi z e d  bl o c k  d esi g n.    R a n d o  mi z ati o n    will  b e  c arri e d  o ut  vi a  c o  m p ut er 
g e n er at e d  r a n d o  m  assi g n  m e nt.   R a n d o  mi z ati o n   m ust  b e  c o  m pl et e d   wit hi n   6  w e e ks  of  d a y  1  of 
st u d y.  
 
A  n o n  -r a n d o  miz e d  pil ot  c o h ort  of  p ati e nts r e c ei vi n g  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y   will  b e 
e nr oll e d  i n   p ar all el  t o   ass ess  t h e  f e asi bilit y   of   S T  A  N  D   cli ni c   p arti ci p ati o n  i n  t his   p ati e nt 
p o p ul ati o n. 
 
7 . 4 D a y  1   St u d y   Visit  
7 . 4. 1 Cli ni c al   Ass ess  m e nt   
•    P h ysi c al  e x a  mi n ati o n  
•    C o n c o  mit a nt   m e di c ati o ns   
•    E  C  O  G  P erf or  m a n c e  St at us  
•    H ei g ht,   w ei g ht,  b o d y    m ass  i n d e x,  a n d  p er c e nt  b o d y  f at  b y  bi oi  m p e d a n c e    m e as ur e  m e nt   
(s e e   A p p e n di x  6) 
•    L  H  R  H   A n al o g u e   
7 . 4. 2 L a b o r at o r y   Ass ess  m e nt   
•    O pti o n al  P eri p h er al  bl o o d  c oll e cti o n f or  g e n ot y pi n g  
•    E xtr a s er u  m  a n d  P  B  M  Cs  c oll e cti o n f or  b a n ki n g  
•    F asti n g li pi d  p a n el  (t ot al  c h ol est er ol, tri gl y c eri d es,  L  D L,   H  D L),  gl u c os e, i ns uli n l e v els 
•    H e  m o gl o bi n   A 1 c 
•    S er u  m  2 5- (  O  H)  vit a  mi n   D l e v el 
•    S er u  m  P S  A  
•    S er u  m t est ost er o n e   
 
7 . 5 D a y  1  a n d   M o nt hl y  St u d y   Visits   ( +/- 2   w e e ks)  
P ati e nts  r a n d o  mi z e d  t o  t h e  S T  A  N  D  cli ni c   will  r et ur n  t o  cli ni c  o n  a    m o nt hl y  b asis.   D uri n g  t h e 
c o urs e   of  t h es e    m o nt hl y   visits,  t h er e    will   b e   a   s eri es   of   s elf -g ui d e d   e d u c ati o n al    m o d ul es 
dis c ussi n g  v ari o us  as p e cts  of  a n dr o g e n  d e pri v ati o n  t h er a p y  a n d    m a n a g e  m e nt  o f  si d e  eff e cts. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
T h es e   m o d ul es   will  b e  c o  m pris e d  of  P o  w er P oi nt  sli d e  pr es e nt ati o ns   w hi c h t h e  p ati e nts   will  vi e  w 
o n  a  s elf -dir e ct e d   m a n n er  d uri n g t h eir  cli ni c  visit,   wit h t h e  o p p ort u nit y t o  as k  q u esti o ns  b ef or e 
a n d  aft er t h e  pr es e nt ati o n.  I n  a d diti o n,  o n  a r ot ati ng  s c h e d ul e,  p ati e nts   will   m e et  o n e -t o-o n e   wit h 
a  li c e ns e d  e x er cis e   tr ai n er,  r e gist er e d  di etiti a n,  a n d  s y  m pt o  m    m a n a g e  m e nt  s er vi c e   t o  r e c ei v e 
i n di vi d u ali z e d  c o u ns eli n g.   T h e  r ot ati o n  of t h e  s c h e d ul e  of  pr o vi d ers   m a y  b e  a dj ust e d  d e p e n di n g 
u p o n  a v ail a bilit y  of  pr o vi d er  a n d  p ati e nt.  I n t ot al,  p ati e nts   will   m e et   with  e a c h s p e ci ali z e d s er vi c e 
f o ur ti  m es  o n  a r ot ati n g  e v er y  3   m o nt h-s c h e d ul e.   
P ati e nts  e nr oll e d  i n  t h e   n o n -r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort    will  r et ur n  t o  cli ni c   o n  a n 
a p pr o xi  m at el y     m o nt hl y   b asis   f or   r ot ati n g   visits     wit h   e x er cis e,   n utriti o n,   a n d   s y  m pt o  m 
m a n a g e  m e nt,   wit h s c h e d ul e  of  visits   m at c hi n g   w h e n e v er  p ossi bl e t h e s c h e d ul e d  d at es  of i nf usi o n 
c e nt er  a p p oi nt  m e nts  
P ati e nts  r a n d o  mi z e d  t o  t h e  st a n d ar d -of -c ar e  ar  m    will  b e  r ef err e d  t o  n utriti o n,  e x er cis e,  a n d 
s y  m pt o  m    m a n a g e  m e nt  s er vi c e   u p o n   p ati e nt  r e q u est   or  if   d e e  m e d   n e c ess ar y   b y   h e alt h  c ar e 
pr o vi d er,   as   p er   c urr e nt   st a n d ar d - of-c ar e   a n d   pr a cti c e   g ui d eli n es.   P ati e nts     w ill   h a v e   t h e 
o p p ort u nit y t o r e c ei v e t h e  e d u c ati o n al   m o d ul es f or r e vi e  w  o utsi d e t h e  cli ni c s etti n g     
D uri n g t h e  c o urs e  of t h e  visit   wit h t h e  e x er cis e tr ai n er,  p ati e nts   will r e vi e  w  e x er cis e  p att er ns   wit h 
t h e  us e  of  q u estio n n air es  fill e d  o ut  pri or  t o  visit  a n d  vi a  t h e  us e  of   a  m b ul at or y  a c c el er o  m et er 
w hi c h   q u a ntifi es  a cti vit y l e v el .  P ati e nts   will r e c ei v e i n di vi d u ali z e d  c o u ns eli n g r e g ar di n g  s p e cifi c 
e x er cis es,  a n d  r ei nf or c e  m e nt  of  est a blis hi n g  r e g ul ar  e x er cis e  r o uti n e.   D uri n g  t h e  c o urs e  of  t h e 
visit,  p ati e nts   w ill  h a v e t h e  o p p ort u nit y t o  pr a cti c e  a ct u al  e x er cis e r o uti n es  u n d er t h e  s u p er visi o n 
of t h e  e x er cis e tr ai n er,  a n d   will r e c ei v e i n -p ers o n  ass ess  m e nt  of  a er o bi c fit n ess l e v el.   
D uri n g t h e  c o urs e  of t h e  visit   wit h t h e r e gist er e d  di etiti a n,  p ati e nts   will r e vi e  w   di et ar y  h a bits  wit h 
t h e  us e  of  di et l o gs  fill e d  o ut  pri or t o  e a c h  visit.  P ati e nts   will r e c ei v e i n di vi d u ali z e d  c ou ns eli n g 
o n r e c o  m  m e n d e d f o o ds/ di et,  a n d   will r e c ei v e f e e d b a c k  o n  pr o gr ess  o n  a l o n git u di n al  b asis.  
D uri n g t h e  c o urs e  of  visit   wit h s y  m pt o  m   m a n  a g e  m e nt s er vi c e,  p ati e nts  p h ysi c al  a n d  ps y c h os o ci al 
iss u es   will  b e  a d dr ess e d  b y  tr ai n e d  h e alt h  c ar e  pr o vi d er.   C o u ns eli n g  a n d    m e di c al   m a n a g e  m e nt 
will  b e  pr o vi d e d.  
7. 6   E v e r y  3  M o nt h   St u d y   Visits ( +/ -  2   w e e ks) 
7. 6 . 1   Cli ni c al   Ass ess  m e nt 
•    P h ysi c al  e x a  m  
•    C o n c o  mit a nt   m e di c ati o ns   
•    E  C  O  G  P erf or  m a n c e  St at us  
•    Q u alit y  of lif e  q u esti o n n air es 
o    S F - 1 2,  E PI C - 2 6,  H F  R  DI S,    L e e   F ati g u e   S c al e,   P  H  Q  -9,    Att e nti o n al   F u n cti o n al 
I n d e x, e x er cis e  p att er n  ass ess  m e nt,  e  m p at h y s c al e  
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
•    W ei g ht,  b o d y   m ass i n d e x,  a n d  p er c e nt  b o d y f at  b y  bi oi  m  p e d a n c e   m e as ur e  m e nt  
•  P ati e nts   will  b e  r ef err e d t o t h e  S y  m pt o  m   M a n a g e  m e nt  S er vi c e ,  n utriti o n  s er vi c e, a n d/ or 
e x er cis e  p h ysi ol o gist  f or f urt h er  e v al u ati o n  at t h e  dis cr eti o n  of  h e alt h  c ar e  pr o vi d er  or  p er 
p ati e nt r e q u est  ( St a n d ar d- of-c ar e tr e at  m e nt  ar  m   o nl y) 
•  L H  R  H  a n al o g u e   a d  mi nistr ati o n  
•  C o u ns eli n g  r e g ar di n g  lif est yl e    m o difi c ati o ns  a n d  r e vi e  w   of  t h e  r es ults   of  t h e  a b o v e 
l a b or at or y  t ests  a n d   q u alit y   of  lif e   q u esti o n n air es   b y  a  tr ai n e d   n urs e   pr a ctiti o n er   or 
p h ysi ci a n.  
o  T h e  P  H  Q -9  q u esti o n n air e  s cr e e ni n g  f or  d e pr essi o n   m ust  b e  c o  m pl et e d i n  p ers o n 
d uri n g t h e  st u d y  visit  a n d   m ust  b e  si g n e d  b y tr e ati n g  h e alt h  c ar e  pr o vi d er  pri or t o 
p ati e nt  dis c h ar g e fr o  m  cli ni c  
7. 6 . 2   L a b o r at o r y   Ass ess  m e nt 
•    S er u  m  a n d  pl as  m a  c oll e cti o n f or  b a n ki n g  
•    F asti n g li pi d  p a n el,  gl u c os e,  a n d i ns uli n l e v el 
•    H e  m o gl o bi n   A 1 c 
•    S er u  m  2 5- (  O  H)  vit a  mi n   D l e v el 
•    S er u  m  P S  A  
7. 7  E n d  of   M o nt h  1 2  St u d y   Visit   ( +/- 2  w e e ks) 
7. 7 . 1   Cli ni c al   Ass ess  m e nt 
•    P h ysi c al  e x a  m  
•    C o n c o  mit a nt   m e di c ati o ns   
•    E  C  O  G  P erf or  m a n c e  S t at us 
•    Q u alit y  of lif e  q u esti o n n air es  
o    S F - 1 2,  E PI C - 2 6,  H F  R  DI  S,    L e e   F ati g u e   S c al e,   P  H  Q -9,    Att e nti o n al   F u n cti o n al 
I n d e x,  e  m p at h y s c al e 
•    W ei g ht,    b o d y   m ass i n d e x,  a n d  p er c e nt  b o d y f at  b y  bi oi  m p e d a n c e   m e as ur e  m e nt 
7. 7 . 2   L a b o r at o r y   Ass ess  m e nt 
•    S er u  m  a n d  pl as  m a f or  b a n ki n g  
•    F asti n g li pi d  p a n el,  gl u c os e,  a n d i ns uli n l e v els 
•    H e  m o gl o bi n   A 1 c 
•    S er u  m  2 5- (  O  H)  vit a  mi n   D l e v els 
•    S er u  m  P S  A  
•    S er u  m t est ost er o n e 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
7. 7 . 3 R a di o g r a p hi c   Ass ess  m e nt   
•    D  X  A  S c a n   
•    Hi g h r es ol uti o n  p eri p h er al  q u a ntit ati v e   C T s c a n  of t h e  dist al ti bi a  a n d r a di us ( o pti o n al)   
7. 8  C o n c o  mit a nt   M e di c ati o ns   
C o n c o  mit a nt    m e di c ati o ns   will  b e  r e c or d e d  at  e a c h   st u d y  visit.  T h e  a d diti o n  of    m e di c ati o ns  t o 
m a n a g e f asti n g  bl o o d  gl u c os e, li pi ds,  b o n e  d e nsit y,  or  bl o o d  pr ess ur e   will  b e  all o  w e d  a n d  at t h e 
dis cr eti o n  of t h e i n di vi d u al tr e ati n g  p h ysi ci a n.  
7. 9  F oll o  w   U p  
P ati e nts  r a n d o  mi z e d t o t h e  st a n d ar d - of-c ar e  st u d y  ar  m   will  h a v e t h e  o pti o n  of  cr ossi n g -o v er t o 
p arti ci p ati o n  i n  t h e  S T  A  N  D  cli ni c  at  t h e  e n d  of    m o nt h  1 2  st u d y  visit.  P ati e nts    w h o  o pt  t o 
p arti ci p at e i n t h e  S T  A  N  D  cli ni c   will  b e f oll o  w e d f or  a n  a d diti o n al  1 2   m o nt hs.  T h e  S T  A  N  D  cli ni c 
s c h e d ul e   will  b e i d e nti c al t o t h at f oll o  w e d  b y  p ati e nts i niti all y r a n d o  mi z e d t o t h e  S T  A  N  D  cli ni c.   
F oll o  wi n g  c o  m pl eti o n  of  S T  A  N  D  cli ni c  p arti ci p ati o n,  p ati e nts    will  b e  f oll o  w e d   b y  t el e p h o n e 
visit  aft er  2  a n d  4   m o nt hs  t o  ass ess a d h er e n c e t o r e c o  m  m e n d e d  di et/ e x er cis e  pl a ns.  At  6   m o nt hs 
f oll o  wi n g  c o  m pl eti o n  of t h e  S T  A  N  D  cli ni c,  p ati e nts   will r et ur n f or  cli ni c  ass ess  m e nt,   w hi c h   will 
i n cl u d e  a  p h ysi c al  e x a  m,  a   m e as ur e  m e nt  of    w ei g ht,  b o d y    m ass  i n d e x,  p er c e nt a g e  b o d y  f at, 
l a b or at or y  t ests  i n cl u di n g  e v al u ati o n  of  f asti n g  gl u c os e/li pi d/i ns uli n  p a n els,  h e  m o gl o bi n    A 1 c,  
pl as  m a   m et a b olit es,   s er u  m   P S  A,   s er u  m   t est ost er o n e    a n d   c o  m pl eti o n   of   q u alit y   of   lif e 
q u esti o n n air es  as  o utli n e d i n t h e   A p p e n di x,  a n d s er u  m  a n d  pl as  m a  b a n ki n g.  
7. 1 0  D u r ati o n  of   St u d y 
T h e t ot al  d ur ati o n  of t h e  st u d y  i n cl u di n g f oll o  w  u p is  e x p e ct e d t o  b e  a p pr o xi  m at el y  5  y e ars fr o  m 
t h e  d at e t h e first  p ati e nt is  e nr oll e d  o nt o st u d y.  
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
8 . A s s e s s  m e nt  of  St u d y  V a ri a bl e s   
 
8 . 1  P e r c e nt   B o d y  F at   Esti  m ati o n 
P er c e nt  b o d y  f at    will  b e  esti  m at e d   at  b as eli n e  a n d  e v er y  3    m o nt hs    wit h  t h e  us e  of  st a n d ar d 
bi o el e ctri c al  i  m p e d a n c e    m o nit or   (s e e    A p p e n di x   4).   Pri or   st u di es   h a v e   d e  m o nstr at e d   hi g h 
r eli a bilit y  a n d str o n g  c orr el ati o n   wit h  ot h er   m o d aliti es i n cl u di n g   D  X  A s c a ns.  
8 . 2  P ati e nt-R e p o rt e d   O ut c o  m es   
At  b  as eli n e  a n d  e v er y  3   m o nt hs  p ati e nts   will  c o  m pl et e  q u alit y  of lif e  a n d  ot h er  q u esti o n n air es  as 
o utli n e d  i n    A p p e n di x  2.  P ati e nts    will  c o  m pl et e  t h e  q u esti o n n air es  o nli n e    wit hi n  o n e    w e e k  of 
st u d y   visit   or   at  t h e  ti  m e   of   st u d y   visit,   eit h er   el e ctr o ni c all y   or   o n   p a p er.    T h e   P  H  Q -9 
q u esti o n n air e    m ust   b e  c o  m pl et e d   o n   p a p er   d uri n g  t h e  st u d y   visit.   It  is    m a n d at or y  t h at  t h e 
r es p o nsi bl e  h e alt h  c ar e  pr o vi d er f or t h e st u d y  visit r e vi e  w  a n d si g n t h e r es ults  of t h e  P  H  Q- 9 pri or 
t o  p ati e nt  dis c h ar g e fr o  m  cli ni c. 
8 . 3 G e r  mli n e  P  ol y  m o r p his  ms 
C oll e cti o n  of  p eri p h er al  bl o o d   m o n o n u cl e ar  c ells f or  ass ess  m e nt  of  g er  mli n e  p ol y  m or p his  ms  a n d 
t h eir  ass o ci ati o n   wit h  t h e  r el e v a nt  t o xi citi es  of   A  D T  is  a n  e x pl or at or y  o bj e cti v e  of  t h e  c urr e nt 
st u d y  a n d  p ati e nt  p arti ci p ati o n i n t his  as p e ct  of t h e st u d y is  o pti o n al.  
T h e  g e n eti c  p ol y  m or p his  ms  s el e ct e d  f or  t his  st u d y    w er e  b as e d  o n  a  lit er at ur e  r e vi e  w  of  pri or 
st u di es    w hi c h   d e  m o nstr at e d  si g nifi c a nt  ass o ci ati o ns   b et  w e e n   p ol y  m or p his  ms   n e ar   or    wit hi n 
s el e ct  g e n es  of i nt er est  e n c o di n g  pr ot ei ns i n v ol v e d i n  st er oi d  h or  m o n e   m et a b olis  m, i ntr a- c ell ul ar 
tr a ns p ort,  estr o g e n/ a n dr o g e n  r e c e pt or  si g n ali n g,  a n d t h e  I  G F  p at h  w a y wit h  cli ni c al  o ut c o  m es  o n 
a n dr o g e n  d e pri v ati o n  t h er a p y.    M ost  pri or  st u di es  i n cl u d e d  p ol y  m or p his  ms  wit h   a    mi n or  all el e 
fr e q u e n c y   >  5  %  i n  t h e    CE  U   (  C a u c asi a n)  p o p ul ati o n.  T h e  f ull  s et   of  p ol y  m or p his  ms  t o  b e 
a n al y z e d is list e d i n   A p p e n di x  1. 
G e n o  mi c   D  N  A   will  b e  pr e p ar e d  fr o  m  p eri p h er al  bl o o d  usi n g  a   QI  A a  m p   D  N  A   Bl o o d   Mi ni   Kit   
(  Q ui a g e n  I n c,   V al e n ci a,   C  A,   U S  A).   D  N  A   will  b e  st or e d  at  4°  C.   G e n ot y pi n g wi  ll  b e  c arri e d  o ut 
usi n g  S e q u e n o  m i P L E  X   m atri x -assist e d l as er  d es or pti o n/i o ni z ati o n  (  M  A L  DI)-ti  m e  of fli g ht   m ass 
s p e ctr o  m etr y   t e c h n ol o g y   (  C arls b a d,     C  A;    htt p://  w  w  w.s e q u e n o  m. c o  m/s e q _ g e n ot y pi n g. ht  ml/). 
Ass a ys   w  ill  b e d esi g n e d  usi n g  S e q u e n o  m’s  M ass  A  R  R  A  Y   Assi g n  D e  si g n er  a p pli c ati o n,  v ersi o n 
3. 0.  P ol y  m er as e  c h ai n  r e a cti o n  ( P  C  R)  a n d  si n gl e  b as e  e xt e nsi o n  ( S  B E)  oli g o n u cl e oti d es   w ill  b e 
s y nt h esi z e d   b y   I nt e gr at e d    D  N  A    T e c h n ol o gi es  (  C or al vill e,   I  A).   P  C  R   a  m plifi c ati o n    will   b e 
p erf or  m e d  usi n g  a n i n p ut  of  1 0  n g  of  D  N  A   i n  a fi n al  v ol u  m e  of  6 L.   T h e  P  C  R  pr o d u cts   w ill  b e 
s u bs e q u e ntl y  tr e at e d   wit h  s hri  m p  al k ali n e  p h os p h at as e,  a n d  t h e  S  B E  r e a cti o ns   w ill  b e i niti at e d 
usi n g i P L E  X  e n z y  m e  a n d   m ass -m o difi e d t er  mi n at ors   ( b ot h  S e q u e n o  m).   Aft er  d es alti n g,  7  n L  of 
t h e  S  B E  r e a cti o n   will  b e s p ott e d  o nt o  a  S p e ctr o  C  HI P  ( S e q u e n o  m)  pr el o a d e d   wit h  7  n L  of   3-
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
h y dr o x y pi c oli ni c  a ci d    m atri x.    T h e  S p e ctr o  C  HI P s    w ill  b e  a n al y z e d  i n  a ut o  m at e d   m o d e  b y  a 
M ass  Arr a y   C o  m p a ct  s oli d  p h as e  l as er    m ass  s p e ctr o  m et er   s yst e  m  (  Br u k er    D alt o ni cs,   Bill eri c a, 
M  A).    T h e   r es ul  ti n g   s p e ctr a  will   b e    a n al y z e d   a n d   g e n ot y p es   c all e d   i n   r e al -ti  m e   b y   t h e 
S p e ctr o  C all er  al g orit h  m,  f oll o  w e d  b y   a d diti o n al  us er -i niti at e d  a n al ysis    wit h  t h e  S p e ctr o T y p er 
v. 3. 4  A ( S e q u e n o  m).  T h e  err or r at e  o n t his  pl atf or  m is  esti  m at e d t o  b e l ess t h a n  0. 0 3  %. 
F or   t h e    mi cr os at ellit e  a n al ysis,  D  N  A  s a  m pl es   will  b e    w h ol e  g e n o  m e  a  m plifi e d    usi n g  I ll ustr a 
G e n o  mi P hi     V 2   a c c or di n g   t o   t h e     m a n uf a ct ur er’s   r e c o  m  m e n d e d   pr ot o c ol   (  G E     H e alt h c ar e, 
C h alf o nt  St   Gill es,   U  K).   T h e y   will  t h e n  b e   q u a ntifi e d  usi n g   R  N  As e P   G e n e  E x pr essi o n   Ass a y 
a c c or di n g t o t h e  m a n uf a ct ur er’s  r e c o  m  m e n d e d  pr ot o c ol   (  A p pli e d   Bi os yst e  ms,   F ost er   Cit y,   C  A, 
U S  A).   P ol y  m er as e  c h ai n  r e a cti o n  ( P  C  R)   will  b e  p erf or  m e d  usi n g  2  μ  M  fi n al  c o n c e ntr ati o n  f or 
b ot h  f or  w ar d   a n d  r e v ers e   pri  m ers,   1. 5    m  m ol/ L    M g,   a n d   0. 2   u nits   of   Pl ati n u  m    T a q    D  N  A 
P ol y  m er as e  (I n vitr o g e n,     C arls b a d,    C  A,    U S  A)  i n   a  fi n al   v ol u  m e   of   1 0 μ L.  Aft er   a n  i niti al 
d e n at ur ati o n  of  5   mi n  at  9 4 °C,   s a  m pl es  will  b e   t hr o u g h  3 5  c y cl es  aft er 9 4°  C f or  4 0  s, t h e  pr o p er 
a n n e ali n g  t e  m p er at ur e f or  3 0  s,  a n d  7 2°  C f or  3 0  s, f oll o  w e d  b y  a fi n al  e xt e nsi o n  st e p  of 7 2°  C f or 
1 0   mi n.   O n e   mi cr olitr e  of  P  C  R  pr o d u ct   will  b e  a d d e d t o  a   mi xt ur e  of   Hi -Di   F or  m a  mi d e (  A p pli e d 
Bi os yst e  ms)  a n d   R  O  X 4 0 0  H  D  St a n d ar d  (  A p pli e d   Bi os yst e  ms).   S a  m pl es   will  t h e n  b e    d e n at ur e d 
f or  5   mi n  at 9 5°  C  a n d  pl a c e d  o n i c e f or  3   mi n, f oll o  w e d  b y  c a pill ar y  el e ctr o p h or esis  o n  a n   A  BI 
3 7 3 0  X L(  A p pli e d    Bi os yst e  ms).    G e n ot y p es   will   b e   s c or e d  usi n g    G e n e  M a p p er   4. 0   (  A p pli e d 
Bi os yst e  ms).   
8. 4   Hi g h   R es ol uti o n  P e ri p h e r al   Q u a ntit ati v e   C  T I  m a gi n g  
T h e i  m a g e  c oll e cti o n   will t a k e  pl a c e  at t h e   C hi n a  B asi n i  m a gi n g f a cilit y  at   U  C S F.   3  D tr a b e c ul ar 
b o n e  d e nsit y  a n d  str u ct ur e,  c orti c al  b o n e  d e nsit y, t hi c k n ess  a n d  p or osit y  at t h e  dist al  r a di us  a n d 
ti bi a  will   b e    m e as ur e d   usi n g   hi g h -r es ol uti o n   p eri p h er al   q u a ntit ati v e  c o  m p ut e d  t o  m o gr a p h y 
(  H  R p  Q  C T). 
R e gi o n al  of  I nt er est   D efi niti o n 
I n t h e  s u p eri or-i nf eri or  dir e cti o n   w e   will  c oll e ct  1 8   m  m  of i  m a g e  d at a,   w e   will  a n al y z e t his  st a c k 
i n t  w o  st a g es, t h e  dist al  9   m  m, t h e n  9   m  m-1 8   m  m.  I n  a d diti o n  r e gi o n al  a n al ysis  f or tr a b e c ul ar 
b o n e,  i n  8  r e gi o ns    will  b e  p erf or  m e d.    T h e   tr a b e c ul ar  c o  m p art  m e nt    will  b e  di vi d e d  i nt o  t  w o 
c o n c e ntri c  r e gi o ns  (i n n er  a n d  o ut er  s u b -r e gi o ns),   w h er e t h e  ar e a  of t h e i n n er  s u b-r e gi o n   will  b e 
6 0  %  of t h e  e ntir e tr a b e c ul ar  r e gi o n.   T h e  v ol u  m e   will  b e  f urt h er  di vi d e d i nt o  a xi al  q u a dr a nts.  I n 
t h e  l e g,   a  li ne   c o n n e cti n g  t h e   a xi al   c e ntr oi ds   of  t h e  ti bi a   a n d  fi b ul a   a n d  it’s   ort h o g o n al 
c o  m pli  m e nt     will    d efi n e   a p pr o xi  m at el y     m e di al -l at er al/ a nt eri or-p ost eri or    q u a dr a nts.   I n   t h e 
f or e ar  m, t h e   m aj or  a n d   mi n or  a x es  of t h e  a xi al  cr oss  s e cti o n  of t h e r a di us   will  d efi n e t h e m e di al  -
l at er al/ a nt eri or-p ost eri or  q u a dr a nts.   E a c h  s u b -r e gi o n  d e n ot e d  b y  a t  w o l ett er  a cr o n y  m  b as e d  o n 
l o c ati o n:  I  or    O  f or  i n n er  or  o ut er  s u b-r e gi o ns,  r es p e cti v el y;  a n d    M,  P,    L,  or    A  f or    m e di al, 
p ost eri or,   l at er al    a n d    a nt eri or,   r es p e cti v el y.     M e a n   tr a b e c ul ar    d e nsit o  m etri c    a n d     mi cr o -
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   3 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
ar c hit e ct ur al i n di c es   will  b e  c o  m p ut e d  f or  e a c h i n di vi d u al  s u b -r e gi o n.   T h e  c orti c al  a n al ysis   will 
b e  d o n e i n t h e  4  a xi al  q u a dr a nts.  
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
9 .  Pl a n n e d  St ati sti c al   M et h o d s 
 
9 . 1 St u d y   D esi g n  
R a n d o  mi z e d,   p h as e   2   st u d y    wit h   cr oss  -o v er   d esi g n  t o   ass ess  t h e  l o n git u di n al  i  m p a ct   of 
p arti ci p ati o n  i n  t h e    m ulti -dis ci pli n ar y  S T  A  N  D  cli ni c   vs.  r e c ei pt  of  us u al  st a n d ar d  of  c ar e   o n 
c h a n g es  i n   k e y    m et a b oli c   p ar a  m et ers,   q u alit y   of  lif e,   a n d   p ati e nt  s atisf a cti o n   a  m o n g    m e n 
r e c ei vi n g  a n dr o g e n  d e pri v ati o n t her a p y f or  pr ost at e  c a n c er.  St a n d ar d -of -c ar e t h er a p y   will  c o nsist 
of  e v er y  3- m o nt h  visits  c o  m pris e d  of r e vi e  w  of   m e di c al  hist or y, t o xi cit y  ass ess  m e nt,  a n d lif est yl e 
m o difi c ati o n  c o u ns eli n g  pr o vi d e d  b y i n di vi d u al  h e alt h  c ar e  pr o vi d er,  L  H  R  H  a n al o g i nj e cti o ns   b y 
tr ai n e d   o n c ol o g y   n urs e.   P ati e nts     will   h a v e   a c c ess   t o   e x er cis e,   n utriti o n,   a n d   s y  m pt o  m 
m a n a g e  m e nt    c o u ns eli n g  if  s o  r e q u est e d  b y  t h e  p ati e nt   or  d e e  m e d  n e c ess ar y  b y  h e alt h  c ar e 
pr o vi d er .    M e n  r a n d o  mi z e d  t o  p arti ci p ati o n  i n  t h e  S T  A  N  D  cli ni c    will  r e c ei v e,  i n  a d diti o n  t o 
st a n d ar d  e v er y  3   m o nt h  visits   wit h  h e alt h  c ar e  pr o vi d ers  a n d   L  H  R  H  a n al o g i nj e cti o ns,   m o nt hl y 
s elf-dir e ct e d  e d u c ati o n al  “  m o d ul es ”  c o v eri n g t h e  v ari o us  as p e cts  of  h or  m o n e t h er a p y  as   w ell  as 
e v er y  3 -m o nt h  i n di vi d u ali z e d  c o u ns eli n g  pr o vi d e d  b y  r e gi  st er e d  di etiti a n,  e x er cis e  tr ai n er,  a n d 
s y  m pt o  m   m a n a g e  m e nt  s er vi c e .   At t h e  e n d  of  1 2   m o nt hs  of  st u d y  p arti ci p ati o n,  p ati e nts i niti all y 
r a n d o  mi z e d t o r e c ei v e st a n d ar d-of -c ar e,   will  h a v e t h e  o pti o n  of  cr ossi n g -o v er t o  p arti ci p at e i n t h e 
S T  A  N  D  cli ni c f or t h e  e ns ui n g  1 2   m o nt hs.  
 
A  n o n  -r a n d o  mi z e d  pil ot  c o h ort  of 2 0  p ati e nts r e c ei vi n g  c o n c urr e nt  c h e  m o h or  m o n al t h er a p y   will 
b e  e nr oll e d  i n  p ar all el  t o  ass ess  t h e  f e asi bilit y  of  S T  A  N  D  cli ni c  p arti ci p ati o n  i n  t his  p ati e nt 
p o p ul ati o n. 
 
9 . 2 D et e r  mi n ati o n  of  S a  m pl e  Si z e  a n d  St u d y  P o  w e r   
T h e  s a  m pl e  si z e  esti  m at e  is  b as e d  u p o n  t h e  pri  m ar y  e n d p oi nt  of  t h e  st u d y,  t h e    m e a n  p er c e nt 
c h a n g e  i n   p er c e nt a g e   b o d y   f at   fr o  m   b as eli n e  t o   1 2    m o nt hs.    B as e d   o n   pri or   pr os p e cti v e 
l o n git u di n al  st u di es,  it  is  esti  m at e d  t h at    m e n  r e c ei vi n g    A  D T  a n d  st a n d ar d- of-c ar e  p h ysi ci a n 
c o u ns eli n g  r e g ar di n g  e x p e ct e d  t o xi citi es    will  e x p eri e n c e  a    m e a n  1 2 %  (  s d  =  1 7  %)  i n cr e as e  i n 
p er c e nt a g e  b o d y f at  aft er  1 2   m o nt hs  of   A  D T [ 1 3].  If   m e n  p arti ci p ati n g i n t h e  S T  A  N  D  cli ni c,   wit h 
i n di vi d u ali z e d  e x er cis e/ n utriti o n  c o u ns eli n g  a n d  l o n git u di n al  ass ess  m e nt,  h a v e,  o n  a v er a g e,  n o 
i n cr e as e  i n  p er c e nt a g e  b o d y  f at    m ass  aft er  1 2    m o nt hs  of  h or  m o n e  t h er a p y,  t his   w o ul d   w arr a nt 
f urt h er  e v al u ati o n  of  a    m ulti-dis ci pli n ar y  cli ni c  i n  a  l ar g er  r a n d o  mi z e d  cli ni c al  tri al   wit h  l o n g -
t er  m  e n d p oi nts  of i nt er est, i n cl u di n g i n ci d e n c e  of  di a b et es  a n d  p ot e nti all y  c ar di o v as c ul ar  dis e as e. 
A n  e nr oll  m e nt t ar g et  of   3 2  e v al u a bl e  p ati e nts  p er  ar  m  will   pr o vi d e  p o  w er  of  8 0  % t o  d et e ct  a n 
eff e ct  si z e  of  0. 7 1   i n  t h e  diff er e n c e  i n    m e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e  t o  1 2    m o nt hs  i n 
p er c e nt a g e  b o d y f at   m ass  b et  w e e n t h e t  w o  ar  ms,  usi n g  a t  w o -s a  m pl e  t t est  a n d  a t  w o-t ail e d l e v el 
of  si g nifi c a n c e   =  0. 0 5.    T h e  t ot al  pl a n n e d  a c cr u al  is   4 0  p ati e nts  p er  ar  m  a c c o u nti n g  f or  a n 
i n e v al u a bl e r at e  of  2 0  %. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A  s a  m pl e  si z e   of   2 0   p ati e nts    is  c h os e n  f or  t h e   n o n-r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort  t o 
est a blis h  t h e  f e asi bilit y  of  a    m ulti -dis ci pli n ar y  cli ni c  i n  t his  p ati e nt  p o p ul ati o n.    T h e  pri  m ar y 
e n d p oi nt  f or t his  pil ot  c o h ort is t h e  p er c e nt a g e  of  c o  m pl et e d  S T  A  N  D  cli ni c  visits,   wit h  a t ar g et 
g o al  of  8 0  %.   A  s a  m pl e  si z e  of  2 0  p ati e nts  ( 1 3  visits  p er  p ati e nt;  2 6 0  visits  i n  t ot al)  pr o vi d es 
1 7. 5  %  pr e cisi o n t o  d et er  mi n e t h e  p er c e nt a g e  of  c o  m pl et e d  visits  at  9 5  %  c o nfi d e n c e. 
 
9 . 3 I nt e ri  m   A n al ysis  
I nt eri  m  a n al ysis   will  b e  p erf or  m e d  aft er  3 3  %  of t h e  pl a n n e d s a  m pl e  si z e  of r a n d o  mi z e d p ati e nts 
c o  m pl et e  1 2 -m o nt h  c ar e.   T o  pr es er v e  t h e  o v er all  t y p e  I  err or  r at e  at  <  0. 0 5,  t h e  L a n -D e  M ets 
s p e n di n g f u n cti o n  will  b e  us e d t o  all o c at e  n o  mi n al  al p h a  -l e v els  at t h e i nt eri  m  a n d fi n al  a n al ys es. 
T h e  effi c a c y  st o p pi n g  b o u n d ar i es  f or  t h e  pri  m ar y  effi c a c y  e n d p oi nt  at  t h e  i nt eri  m  a n d  fi n al 
a n al ys es  ar e  p   <  0. 0 2 6 a n d  p   <  0. 4 7 4, r es p e cti v el y.  
 
A n i nt eri  m  a n al ysis f or t h e  n o n  -r a n d o  mi z e d  c o h ort   will  b e  p erf or  m e d  aft er  1 0  p ati e nts  h a v e  b e e n 
e nr oll e d  o n  t h e  S T  A  N  D  cli ni c  f or  a    mi ni  m u  m   of  6    m o nt hs.  If  t h e  p er c e nt a g e  of  c o  m pl et e d 
S T  A  N  D  visits  is  l ess  t h a n  6 0  %,  t h e  st u d y  s c h e d ul e    will  b e  alt er e d  t o  e ns ur e  hi g h er  r at es  of 
p ati e nt  a d h er e n c e t o t h e  cli ni c s c h e d ul e.  
 
9. 4   A c c r u al 
A  t ot al  of   8 0   p ati e nts    will  b e  e nr oll e d   i n  t h e  r a n d o  mi z e d  p ati e nt  c o h ort  at  t h e    U ni v ersit y  of 
C alif or ni a  S a n  Fr a n cis c o.   St u d y  a c cr u al is  a nti ci p at e d t o  b e  a p pr o xi  m at el y  2  p ati e nts  p er   m o nt h, 
l e a di n g t o t ot al  st u d y  a c cr u al  d ur ati o n  of 4 0  m o nt hs.   A nti ci p at e d ti  m e fr o  m l ast  p ati e nt  e nr oll e d 
t o   pri  m ar y   st u d y   c o  m pl eti o n   a n d   a n al ysis   of   pri  m ar y   a n d   s e c o n d ar y   e n d p oi nts   e q u als 
a p pr o xi  m at el y  1 2   m o nt hs, l e a di n g t o  a n  esti  m at e d  pri  m ar y  st u d y  d ur ati o n  of  5 2   m o nt hs.  A t ot al 
of  2 0  p ati e nts   will  b e  e nr oll e d  i n  t h e  n o n -r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort,  at  a n  esti  m at e d 
fr e q u e n c y  of  0. 8  p ati e nts/  m o nt h, l e a di n g t o  a n  esti  m at e d  a c cr u al  p eri o d  of  2 4   m o nt hs. 
 
9. 5  A n al ysis  P o p ul ati o ns   
T h e  pri  m ar y   a n al ysis  f or t h e r a n d o  mi z e d  c o h ort  will i  n cl u d e  all  p ati e nts   w h o  h a v e  a  b o d y f at   % 
m e as ur e  m e nt   at  b as eli n e  a n d  at   m o nt h  1 2  o n  st u d y  ( +/ -  2   w e e ks).  If  a p ati e nt  c o  m es  off  st u d y 
pri or t o  o bt ai ni n g t h e  e n d  of   m o nt h  1 2  b o d y f at   %   m e as ur e  m e nt, t h e y   will  n ot  b e i n cl u d e d i n t h e 
pri  m ar y st u d y  a n al ysis.  
All  p ati e nts  e nr oll e d  i n  t h e  c h e  m o h or  m o n al  n o n  -r a n d o  mi z e d  c o h ort   w h o  c o  m pl et e   C 1  D 1  visit 
will  b e i n cl u d e d i n t h e  a n al ysis  of t h e  pri  m ar y  e n d p oi nt, t h e  p er c e nt a g e  of  c o  m pl et e d  visits i n t h e 
S T  A  N  D  cli ni c.  
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
9. 6  D e  m o g r a p hi cs  a n d   B as eli n e   C h a r a ct e risti cs   
D e  m o gr a p hi c  v ari a bl es   will i n cl u d e  a g e, r a c e,   a n d  et h ni cit y.   B as eli n e  c h ar a ct eristi cs   will i n cl u d e  
t h e f oll o  wi n g: 
o    H ei g ht,   w ei g ht,  b o d y   m ass i n d e x,   w aist  cir c u  mf er e n c e,  p er c e nt a g e  b o d y f at 
o    Ass ess  m e nt  of  c o  -  m or bi diti es i n cl u di n g  di a b et es  a n d  h e art  dis e as e (  A p p e n di x  3) 
o    D at e  of  pr ost at e  c a n c er  di a g n osis   
o    Gl e as o n  gr a d e  a n d  P S  A  at t h e ti  m e  of  di a g n osis 
o    T y p e  a n d  d at e  of  pri or  l o c al t h er a p y (if  a n y) 
o    D at e   of    A  D T  i niti ati o n  a n d  i n di c ati o n  ( a dj u v a nt,   bi o c h e  mi c al  r el a ps e,   or    m et ast ati c 
dis e as e)  
o    B as eli n e  P S  A  at t h e st art  of   A  D T    
o    C o n c urr e nt  us e  of  a nti- a n dr o g e n 
o    M et ast ati c st at us  at ti  m e  of st u d y  e ntr y ( n o n e,  b o n e  o nl y, s oft tiss u e,  a  n y  vis c er al)  
 
9. 7  St u d y   E n d p oi nts  
9. 7 . 1  P ri  m a r y   E n d p oi nt 
 
R a n d o  mi z e d  c o h o rt:   M e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e t o  1 2   m o nt hs   i n  p er c e nt a g e  b o d y  f at 
m ass  as   m e as ur e d  b y  bi o el e ctri c al i  m p e d a n c e  a n al y z er.    
 
N o n  - r a n d o  mi z e d  c o h o rt: P er c e nt a g e  of  c o  m pl et e d  S T  A  N  D  cli ni c  visits.  
 
9. 7 . 2  S e c o n d a r y   E n d p oi nts 
M e a n  p e r c e nt   c h a n g e  f r o  m  b as eli n e  t o  1 2    m o nt hs  a n d  p att e r ns  of  c h a n g e  f r o  m  b as eli n e  
wit h  r es p e ct t o t h e f oll o  wi n g  : 
 
M et a b oli c I  m p a ct  o n   Di a b et es  a n d   C ar di o v as c ul ar   Dis e as e  Ris k  F a ct ors:    
-   F asti n g  bl o o d  gl u c os e 
-   F asti n g  pl as  m a i ns uli n l e v el  
-   I ns uli n r esist a n c e  as  c al c ul at e d  b y   H  O  M  A-I R 
-   H e  m o gl o bi n   A 1 c 
-   F asti n g li pi ds (t ot al  c h ol est er ol,  L  D L,   H  D L, tri gl y c er ci d es)  
-   W aist  cir c u  mf er e n c e   
-   B o d y   w ei g ht/ b o d y   m ass i n d e x 
-   E x er cis e  p att er ns  as   m e as ur e d  b y  v ali d at e d  q u esti o n n air e  a n d  p e d o  m et er  ass ess  m e nt   
-   Bl o o d  pr ess ur e 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
B o n e   H e alt h:   
-   B o n e  d e nsit y  at t h e l u  m b ar  s pi n e,  f e  m or al  n e c k,  a n d t ot al  hi p  as  ass ess e d  b y   D  X  A  s c a n 
a  m o n g  p ati e nts   wit h o ut  b o n e   m et ast as es  at t h e ti  m e  of st u d y  e ntr y  
-   S er u  m  2 5- (  O  H)  vit a  mi n   D l e v els 
 
Q u alit y  of  Lif e/ Ps y  c h os o ci al I  m p a ct:  
-   D e pr essi o n  as   m e as ur e d  b y  P  H  Q  - 9 
-   C o g niti v e f u n cti o n  as   m e as ur e d  b y   Att e nti o n al  F u n cti o n al I n d e x 
-   O v er all  q u alit y  of lif e  as   m e as ur e d  b y  S F  - 1 2 
-   F ati g u e  as   m e as ur e d  b y t h e  L e e  F ati g u e  S c al e  
-   Er e ctil e   a n d  uri n ar y f u n cti o n  as   m e as ur e d  b y E PI  C - 2 6 
-   H ot fl as h s e v erit y  as   m e as ur e d  b y   H ot  Fl as h   R el at e d   D ail y I nt erf er e n c e  S c al e   
 
9. 7 . 3   C o r r el ati v e  St u d y   E n d p oi nts 
 
-      Ass o ci ati o n  b et  w e e n  i n h erit e d  g e n eti c  p ol y  m or p his  ms  of  f u n cti o n al  r el e v a n c e  n e ar  or 
wit hi n   g e n es  e n c o di n g  pr ot ei ns    wit h  r ol es  i n  st er oi d  h or  m o n e  tr a ns p ort  a n d  a n dr o g e n 
r e c e pt or   si g n ali n g    wit h   c h a n g es  i n    m et a b oli c   p ar a  m et ers   a  m o n g    m e n  tr e at e d    wit h 
a n dr o g e n  d e pri v ati o n t h er a p y. 
-   
M e a n  c h a n g e  fr o  m  b as eli n e  i n  tr a b e c ul ar  b o n e  ar c hit e ct ur e  as    m e as ur e d  b y  tr a b e c ul ar 
b o n e  n u  m b er  ( T b  N)  a n d  tr a b e c ul ar  b o n e  v ol u  m e  fr a cti o n  (  B  V/ T  V)  aft er  1 2   m o nt hs  of 
a n dr o g e n  d e pri v ati o n t h er a p y. 
-   
Ass o ci ati o n  b et  w e e n  2  D: 4  D r ati o   wit h  c h a n g e i n  q u alit y  of lif e  o n  a n dr o g e n  d e pri v ati o n 
t h er a p y. 
-   
Ass o ci ati o n  b et  w e e n  2  D: 4  D  r ati o  a n d  b as eli n e  a n d  p er c e nt  c h a n g e  fr o  m  b as eli  n e  i n 
e  m p at h y s c or e.  
 
9. 8  M et h o ds f o r   A n al ysis   
G e n er all y,  fr e q u e n c y  distri b uti o ns,    m e a ns,  a n d  st a n d ar d  d e vi ati o ns    will  b e  us e d  t o  d es cri b e 
s u bj e ct  d e  m o gr a p hi cs  a n d  b as eli n e  c h ar a ct eristi cs.   U ni v ari at e  a n al ysis  a  m o n g  v ari a bl es   will  b e 
ass ess e d  usi n g  t h e  t  w o -s a  m pl e  t-t est,    Wil c o x o n-r a n k-s u  m  t est,   C hi-s q u ar e  t est,  as  a p pr o pri at e. 
St atisti c al  si g nifi c a n c e    will  b e  d e cl ar e d  b as e d  o n  al p h a  l e v el  of  0. 0 5.  F or  t h e  e n d p oi nts    wit h 
missi n g l ess t h a n  2 5  %   of  v al u es,  m ulti v ari at e i  m p ut ati o n  usi n g f ull y  c o n diti o n al  s p e cifi c ati o n (  R 
MI C E  p a c k a g e)    will  b e  i  m pl e  m e nt e d  .  F or  e n d p oi nts    missi n g    m or e  t h a n  2 5  %  of  v al u es,  t h e 
e n d p oi nt   will  b e  e x cl u d e d fr o  m t h e fi n al  a n al ysis.  
 
9. 8 . 1 A n al yti c  Pl a n f o r t h e  P ri  m a r y   O bj e cti v e   
T  w o -sa  m pl e t -t est   will  b e  us e d t o  c o  m p ar e t h e   m e a n  p er c e nt  c h a n g e fr o  m  b as eli n e i n  p er c e nt a g e 
b o d y  f at  aft er  1 2   m o nt hs  of  st u d y  p arti ci p ati o n.   T h e  c h a n g es i n  p er c e nt a g e  b o d y  f at  a cr oss t h e 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
diff er e nt ti  m e  p oi nts   will  b e  e v al u at e d  usi n g r e p e at e d   m e as ur es  a n al ysis   of  c o v ari a n c e.  T o f urt h er 
c h ar a ct eri z e t h e  p att er ns  o v er t h e ti  m e  a n d i n v esti g at e t h e  eff e ct  of  tr e at  m e nt  ar  m  assi g n  m e nt,  a 
li n e ar    mi x e d    m o d el    will   b e  a p pli e d    wit h  a dj usti n g  f or  str atifi c ati o n  f a ct ors  a n d   c o v ari at es 
i n cl u di n g C h arls o n  c  o- m or bi dit y i n d e x  s c or e,  a g e,   a n d  b as eli n e  d e pr essi o n  s c or e  as   m e as ur e d  b y 
P  H  Q -9.   P ati e nts     w h o   d o   n ot   h a v e   a   b as eli n e   or   e n d - of-m o nt h   1 2   p er c e nt a g e   b o d y   f at 
m e as ur e  m e nt,  or  t h os e  t h at  st art    m e di c ati o ns   k n o  w n  t o  aff e ct  b o d y  f at/ b o d y   w ei g ht  d uri n g  t h e 
c o urs e  of  t h e  1 2 -m o nt h  st  u d y ,  i n cl u di n g    m etf or  mi n,  i ns uli n,  c orti c ost er oi ds,    mirt a z a pi n e,  or 
m e g estr ol  ,   will  b e  e x cl u d e d fr o  m t h e  pri  m ar y  e n d p oi nt  a n al ysis. I n  a n  e x pl or at or y  a n al ysis, t h es e 
p ati e nts    will  b e  r et ai n e d  t o  ass ess  t h e  i  m p a ct  of  S T  A  N  D  cli ni c  p arti ci p ati o n  o n   c h a n g es  i n  
p er c e nt a g e  b o d y f at  o v er ti  m e  b ot h  b ef or e  a n d  aft er i niti ati o n  of   m e di c al   m a n a g e  m e nt.  
 
F or t h e  n o n -r a n d o  mi z e d  c h e  m o h or  m o n al  c o h ort, t h e  p oi nt  esti  m at e  a n d  9 5  %  c o nfi d e n c e i nt er v al 
of t h e  p er c e nt a g e  of  c o  m pl et e d  S T  A  N  D  cli ni c  visits   will  b e r e p ort e d. 
 
9. 8 . 2 A n al yti c  Pl a n f o r t h e  S e c o n d a r y   O bj e cti v es   
T  w o -s a  m pl e t t est   will  b e  us e d t o  c o  m p ar e t h e   m e a n  c h a n g e fr o  m  b as eli n e t o  1 2   m o nt hs f or t h e 
s e c o n d ar y  e n d p oi nts   w hi c h  h ol d  t h e  n or  m alit y  ass u  m pti o n.  F or   e n d p oi nts t h at d o  n ot  h ol d  t h e 
n or  m alit y  ass u  m pti o n,  as  w ell  as f or   or di n al l e v el  of   m e as ur e  m e nts,   Wil c o x o n -r a n k-s u  m t est   will 
b e   us e d.    T o  e v al u at e  t h e  c h a n g es  i n  s e c o n d ar y   e n d p oi nts  a cr oss  t h e   diff er e nt  ti  m e   p oi nts, 
r e p e at e d    m e as ur es  a n al ysis  of  c o v ari a n c e    will  b e  us e d  f or  c o nti n u o us  e n d p oi nts  ( a p pr o pri at e 
tr ansf or  m ati o n   will  b e  a p pli e d  if  n or  m alit y  ass u  m pti o n  d o es n’t  h ol d),   w hil e  r e p e at e d   m e as ur es 
g e n er ali z e d  esti  m ati o n  e q u ati o n    wit h   a  c u  m ul ati v e  l o gi c   c at e g ori c al    will  b e  a p pli e d  f or  t h e 
or di n al   l e v el    of     m e as ur e  m e nts.     G e n er ali z e d   li n e ar     mi x e d     m o d els     wit h   a dj us tm e nt     f or 
str atifi c ati o n  f a ct ors  a n d  p ossi bl e  c o v ari at es   will  b e  a p pli e d  t o  f urt h er  c h ar a ct eri z e  t h e  p att er ns 
o v er t h e ti  m e  a n d i n v esti g at e t h e  eff e ct  of t h e  c ar e t y p e   wit h  a p pr o pri at e li n k  f u n cti o n.   R es ults 
will  b e  dis pl a y e d i n  a  gr a p hi c al f as hi o n.   P ati e n ts   w h o  st art   m e di c ati o ns  k n o  w n t o  aff e ct  e n d p oi nt 
b ei n g  a n al y z e d  ( e. g.  st ati ns  f or  t h e  li pi d  p a n el    m e as ur e  m e nt)    will  b e  e x cl u d e d  fr o  m  t h e    m ai n 
st atisti c al  a n al ysis.  I n  a  s e nsiti vit y  a n al ysis  t h es e  p ati e nts   will  b e  r et ai n e d  t o  ass ess  i  m p a ct  of 
S T  A  N  D  cli ni c  p arti ci p ati o n  o n  st u d y  o ut c o  m es.  N o  a dj ust  m e nt f or   m ulti pl e  c o  m p aris o ns   will  b e 
m a d e f or t h e  a n al ysis  of t h e s e c o n d ar y,  e x pl or at or y  o bj e cti v es.   
 
F or  p ati e nts   w h o  cr oss -o v er fr o  m  st a n d ar d - of-c ar e t o  p arti ci p at e i n t h e  S T  A  N  D  cli ni c, t h e   m e a n 
c h a n g e  fr o  m   m o nt h  1 2  t o   m o nt h  2 4  aft er  t  w el v e   m o nt hs  of  p arti ci p ati o n  i n  t h e  S T  A  N  D  cli ni c 
wit h r es p e ct t o t h e st u d y  e n d p oi nts   will  b e  d es cri pti v el y r e p ort e d.  
 
D uri n g  t h e  f oll o  w  -u p  p h as e  of  t h e  st u d y,  t h e    m e a n  c h a n g e  fr o  m  c o  m pl eti o n  of  S T  A  N  D  cli ni c 
p arti ci p ati o n t o  1 2   m o nt hs  aft er  c o  m pl eti o n   wit h r es p e ct t o  st u d y  e n d p oi nts   will  b e  d es cri pti v el y 
r e p ort e d.  
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
9. 8 . 3   A n al yti c  Pl a n f o r t h e   C o r r el ati v e   O bj e cti v es 
T h e r el ati o ns hi p  b et  w e e n  e a c h   pr e-s el e ct e d S  N P  g e n ot y p e  a n d t h e  p er c e nt  c h a n g e fr o  m  b as eli n e 
t o  1 2   m o nt hs  o n-st u d y i n  p er c e nt a g e  b o d y  f at,  f asti n g  pl as  m a  gl u c os e,  b o d y   m ass i n d e x,   w aist 
cir c u  mf er e n c e,  a n d f asti n g i ns uli n  a  m o n g   m e n  u n d er g oi n g   A  D T   will  e a c h  b e t est e d  usi n g  a t  w o -
s a  m pl e  t  t est  or    Wil c o x o n -r a n k-s u  m  t est  as  a p pr o pri at e    w h e n  t h e  S  N Ps  ar e  i n  d o  mi n a nt  or 
r e c essi v e  f as hi o n.    W h e n  S  N Ps  ar e  i n  t h e  a d diti v e    m o d el,  f or  e a c h  S  N P,  a  g e n er ali z e d  li n e ar 
m o d el   wit h  a n    a p pr o pri at e li n k   will  b e  us e d  c o nsi d eri n g  e a c h b as eli n e -1 2   m o nt h  c h a n g e  as  t h e 
r es p o ns e  v ari a bl e  a n d  S  N P  g e n ot y p e ( c o d e d  as  0,  1,  a n d  2 f or  z er o,  o n e  a n d t  w o  c o pi es  of   mi n or 
all el e)  as  t h e  pr e di ct or.   A n al ysis   will  b e  e xt e n d e d  t o  a dj ust  f or  p ossi bl e  ris k  f a ct ors  b y  fitti n g 
m ulti v ari at e   g e n er ali z e d   li n  e ar     m o d els   f or   e a c h  b as eli n e -1 2     m o nt h   c h a n g e  a n d   e a c h   S  N P. 
M ulti pl e t esti n g  a dj ust  m e nts   will  b e  d o n e f or  e a c h   b as eli n e -1 2   m o nt h  c h a n g e  a cr oss  all  S  N Ps  b y 
c o ntr olli n g f or f als e  dis c o v er y r at e. 
T h e    m e a n   p er c e nt   c h a n g e   fr o  m   b as eli n e  i n  tr a b e c ul ar   b o n e    mi cr o ar c hit e ct ur e   p ar a  m et ers 
i n cl u di n g  tr a b e c ul ar   b o n e   n u  m b er  a n d  tr a b e c ul ar   b o n e   v ol u  m e  ass ess e d   b y   hi g h  r es ol uti o n 
q u a ntit ati v e  p eri p h er al   C T   will  b e  d es cri pti v el y  r e p ort e d  f or  t h e  e ntir e  st u d y  p o p ul ati o n.  I n  a n 
e x pl or at or y  f as hi o n, t h e   m e a n  p er c e nt  c h a n g e  b et  w e e n t h os e  r a n d o  mi z e d t o t h e  S T  A  N  D  v ers us 
us u al  c ar e tr e at  m e nt  ar  ms   will  b e  c o  m p ar e d  usi n g   M a n n -W hit n e y t est.   
T h e   distri b uti o n   of  t h e   2  D: 4  D  fi n g er  l e n gt h  r ati o    will   b e   d et er  mi n e d  f or  t h e   e ntir e  st u d y 
p o p ul ati o n.   As  t h e  o pti  m al  c ut -off  t o  d efi n e  s e nsiti vit y  t o  a n dr o g e n  d e pri v ati o n  t h er a p y  is  n ot 
k n o  w n, t h e  st u d y  c o h ort   will  b e  di c h ot o  mi z e d i nt o t h os e   wit h  2  D: 4  D r ati os  a b o v e  a n d  b el o  w t h e 
m e di a n  r es p e cti v el y.   T h e   m e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e i n   Q  O L  s c or es  fr o  m t h e  c oll e ct e d 
q u esti o n n air es  as   w ell  as t h e  b as eli n e  a n d   m e a n  p er c e nt  c h a n g e  fr o  m  b as eli n e i n  e  m p at h y  s c or e 
will  b e  c o  m p ar e d  b et  w e e n  di c h ot o  mi z e d s u b gr o u ps  usi n g t h e   M a n n-  W hit n e y t est.   
N o  a dj ust  m e nt  f or   m ulti pl e  c o  m p aris o ns   will  b e    m a d e  f or  t h e  a n al ysis  of  t h e  c orr el ati v e  st u d y 
e n d p oi nts. 
   
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1 0 . St u d y   M a n a g e  m e nt  
1 0. 1  P r e- st u d y   D o c u  m e nt ati o n  
T his  st u d y   will  b e  c o n d u ct e d i n  a c c or d a n c e   wit h  t h e  et hi c al  pri n ci pl es t h at  h a v e t h eir  ori gi n i n 
t h e    D e cl ar ati o n  of    H elsi n ki  as  st at e d  i n  2 1   C F  R  § 3 1 2. 1 2 0( c)( 4);  c o nsist e nt    wit h    G  C P  a n d  all 
a p pli c a bl e r e g ul at or y  r e q uir e  m e nts. 
 
B ef or e  i niti ati n g  t his  tri al,  t h e  I n v esti g at or   will    h a v e    writt e n   a n d   d at e d  a p pr o v al  fr o  m  t h e 
I nstit uti o n al   R e vi e  w   B o ar d f or t h e  pr ot o c ol,   writt e n i nf or  m e d  c o ns e nt  f or  m,  s u bj e ct  r e cr uit  m e nt 
pr o c e d ur es  ( e. g.,  a d v ertis e  m e nts),  a n d  a n y  ot h er   wr itt e n i nf or  m ati o n t o  b e  pr o vi d e d t o  s u bj e cts 
b ef or e  a n y  pr ot o c ol r el at e d  pr o c e d ur es  ar e  p erf or  m e d  o n  a n y s u bj e cts.   
 
T h e I n v esti g at or   m ust  c o  m pl y   wit h t h e  a p pli c a bl e r e g ul ati o ns i n   Titl e  2 1  of t h e   C o d e  of  F e d er al 
R e g ul ati o ns  ( 2 1    C F  R)   P arts   § 5 0,   § 5 4,   a n d   §  3 1 2,   G  C P/I C  H   g ui d eli n es,   a n d   all   a p pli c a bl e 
r e g ul at or y  r e q uir e  m e nts.     T h e  I R  B  m ust   c o  m pl y    wi  t h  t h e  r e g ul ati o ns  i n   2 1    C F  R   5 6   a n d 
a p pli c a bl e r e g ul at or y r e q uir e  m e nts.  
 
1 0 . 2 I nstit uti o n al   R e vi e  w   B o a r d   A p p r o v al  
T h e  pr ot o c ol,  t h e  pr o p os e d  i nf or  m e d  c o ns e nt   f or  m,  a n d  all  f or  ms  of  p arti ci p a nt  i nf or  m ati o n 
r el at e d  t o  t h e  st u d y  ( e. g.  a d v ertis e  m e nts  us e d  t o  r e cr uit  p arti ci p a nts)    will  b e  r e vi e  w e d  a n d 
a p pr o v e d   b y   t h e    C o  m  mitt e e   o n    H u  m a n    R es e ar c h  (  U  C S F’s  I R  B).     Pri or  t o   o bt ai ni n g    C  H  R 
a p pr o v al,  t h e  pr ot o c ol    m ust  b e  a p pr o v e d   b y  t h e    H el e n    Dill er  F a  mil y    C o  m pr e h e nsi v e   C a n c er 
C e nt er   Pr ot o c ol   R e vi e  w   C o  m  mitt e e  ( P R  C).     T h e  i niti al  pr ot o c ol  a n d  all  pr ot o c ol  a  m e n d  m e nts 
m ust  b e  a p pr o v e d  b y t h e I  R  B  pri or t o i  m pl e  m e nt ati o n.  
  
1 0 . 3 I nf o r  m e d   C o ns e nt  
All  p arti ci p a nts   m ust   b e  pr o vi d e d  a  c o ns e nt f or  m  d es cri bi n g t h e st u d y   wit h s uffi ci e nt i nf or  m ati o n 
f or  p arti ci p a nts  t o    m a k e  a n  i nf or  m e d  d e cisi o n  r e g ar di n g  t h eir  p arti ci p ati o n.   P arti ci p a nts    m ust 
si g n  t h e  I R  B-a p pr o v e d  i nf or  m e d   c o ns e nt   f or  m  pri or  t o   p arti ci p ati o n  i n   a n y  st u d y  s p e cifi c 
pr o c e d ur e.   T h e  p arti ci p a nt   m ust r e c ei v e  a  c o p y  of t h e  si g n e d  a n d  d at e d  c o ns e nt  d o c u  m e nt.   T h e 
ori gi n al  si g n e d  c o p y  of t h e  c o ns e nt  d o c u  m e nt   m ust  b e r et ai n e d i n t h e   m e di c al r e c or d  or r es e ar c h 
fil e.  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1 0 . 4 C h a n g es i n t h e  P r ot o c ol   
O n c e t h e  pr ot o c ol  h as  b e e n  a p pr o v e d  b y t h e   U  C S F   C o  m  mitt e e  o n   H u  m a n   R es e ar c h (  C  H  R),  a n y 
c h a n g es  t o  t h e  pr ot o c ol    m ust  b e  d o c u  m e nt e d  i n  t h e  f or  m  of  a n  a  m e n d  m e nt.     T h e  a  m e n d  m e nt 
m ust  b e si g n e d  b y t h e I n v esti g at or  a n d  a p pr o v e d  b y  P  R  C  a n d t h e   C  H  R  pri or t o i  m pl e  m e nt ati o n.   
If  it  b e c om es  n e c ess ar y  t o  alt er  t h e  pr ot o c ol  t o  eli  mi n at e  a n  i  m  m e di at e  h a z ar d  t o  p ati e nts,  a n 
a  m e n d  m e nt    m a y  b e  i  m pl e  m e nt e d  pri or  t o   C  H  R  a p pr o v al.    I n  t his  cir c u  mst a n c e,  h o  w e v er,  t h e 
I n v esti g at or     m ust   t h e n   n otif y   t h e     C  H  R   i n     writi n g     wit hi n   fi v e   ( 5)     w or ki n g   d a ys   aft er  
i  m pl e  m e nt ati o n. 
 
1 0 . 5 C as e   R e p o rt  F o r  ms (  C  R Fs)   
T h e   Pri n ci p al  I n v esti g at or    a n d/or   his/ h er   d esi g n e e   will   pr e p ar e   a n d    m ai nt ai n   a d e q u at e   a n d 
a c c ur at e  p arti ci p a nt  c as e  hist ori es    wit h  o bs er v ati o ns  a n d  d at a  p erti n e nt  t o  t h e  st u d y.     St u d y 
s p e cifi c  C as e   R e p ort  F or  ms  (  C  R Fs)   will   d o c u  m e nt  tr e at  m e nt  o ut c o  m es  f or  d at a  a n al ysis . st u d y 
d at a    will  b e  e nt er e d  i nt o   O n  C or e  ®  a n d   R e d  C  A P, U  C S F’s   Cli ni c al   Tri al    M a n a g e  m e nt  S yst e  m 
(  C T  M S)  vi a st a n d ar di z e d   C  R Fs  i n  a c c or d a n c e   wit h t h e   C T  M S  st u d y  c al e n d ar, usi n g  si n gl e  d at a 
e ntr y   wit h  a  s e c ur e  a c c ess  a c c o u nt.   T h e   Cli ni c al   R es e ar c h   C o or di n at or (  C  R  C)   will  c o  m pl et e t h e 
C  R Fs   as  s o o n  as  p ossi bl e  u p o n  c o  m pl eti o n  of  t h e  st u d y  visit;  t h e  I n v esti g at or   will  r e vi e  w  a n d 
a p pr o v e t h e  c o  m pl et e d   C  R Fs.  
 
T h e  i nf or  m ati o n   c oll e ct e d   o n    C  R Fs  s h all   b e   i d e nti c al  t o  t h at   a p p e ari n g  i n   ori gi n al  s o ur c e 
d o c u  m e nts.    S o ur c e  d o c u  m e nts    will  b e  f o u n d  i n  t h e  p ati e nt’s    m e di c al  r e c or ds    m ai nt ai n e d  b y 
U  C S F  p ers o n n el.    All  s o ur c e  d o c u  m e nt ati o n  s h o ul d  b e  k e pt i n  s e p ar at e r es e ar c h f ol d ers f or  e a c h 
p ati e nt.  
 
I n  a c c or d a n c e    wit h  f e d er al  r e g ul ati o ns,  t h e  I n v esti g at or  is  r es p o nsi bl e  f or  t h e  a c c ur a c y  a n d 
a ut h e nti cit y  of  all  cli ni c al  a n d l a b or at or y  d at a  e nt er e d  o nt o   C  R Fs.   E a c h   C  R F   m ust  b e r e vi e  w e d 
f or  a c c ur a c y  b y t h e  I n v esti g at or,  c orr e ct e d  as  n e c ess ar y,  a n d t h e n  a p pr o v e d.    Alt er n ati v el y, t h e 
I n v esti g at or    m a y  si g n  i n di vi d u al,  pri nt e d    C  R Fs.     T h es e  si g n at ur es  att est  t h at  t h e  i nf or  m ati o n 
c o nt ai n e d  o n t h e   C  R Fs is tr u e  a n d  a c c ur at e.  
 
All  s o ur c e  d o c u  m e nt ati o n  a n d   C T  M S  d at a   will  b e  a v ail a bl e  f or  r e vi e  w/  m o nit ori n g  b y t h e   D at a 
a n d  S af et y   M o ni t ori n g   C o  m  mitt e e (  D S  M  C)  a n d r e g ul at or y  a g e n ci es. 
 
T h e  Pri n ci p al I n v esti g at or   will  b e r es p o nsi bl e f or  e ns uri n g t h e  a c c ur at e  c a pt ur e  of  st u d y  d at a.    At 
st u d y  c o  m pl eti o n,   w h e n  t h e  d at a b as e  h as  b e e n  d e cl ar e d t o  b e  c o  m pl et e  a n d  a c c ur at e, t h e  d at a b as e 
will  b e l o c k e d.    A n y  c h a n g es t o t h e  d at a b as e  aft er t h at ti  m e  c a n  o nl y  b e   m a d e  b y j oi nt   writt e n 
a gr e e  m e nt  a  m o n g   t h e  Pri n ci p al  I n v esti g at or ,  t h e    Tri al   St atisti ci a n,  a n d  t h e   Pr ot o c ol   Proj e ct 
M a n a g er.   
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
1 0 . 6 R et e nti o n  of   R e c o r ds   
T h e   I n v esti g at or   a gr e es  t o    m ai nt ai n   a   c o  m pl et e   a n d   c urr e nt   r e c or d   of   all   d o c u  m e nt ati o n 
ass o ci at e d   wit h t h e  st u d y.    All  of t h e  d o c u  m e nts  s h all  b e  k e pt t o g et h er.   E a c h  s h o ul d  b e  a v ail a bl e 
f or r e a d y r e vi e  w.   T h es e st ud y  d o c u  m e nts   will i n cl u d e t h e: 
•    pr ot o c ol 
•    pr ot o c ol  a  m e n d  m e nts,   w h e n  a p pli c a bl e 
•    I n v esti g at or’s  c urr e nt  c urri c ul u  m  vit a e 
•    d o c u  m e nt ati o n  of    C  H  R  a p pr o v als  f or  t h e  pr ot o c ol,  a  m e n d  m e nts,  i nf or  m e d  c o ns e nts  a n d 
a d v ertis e  m e nts  us e d t o r e cr uit  p ati e nts   
•    sit e  visit l o g 
•    c orr es p o n d e n c e ( all  “t o ”  a n d  “fr o  m ”  c orr es p o n d e n c e)  
•    c as e r e p ort f or  ms  a n d i nf or  m e d  c o ns e nt  d o c u  m e nts f or i n di vi d u al  p ati e nts 
•    fi n al r e p ort f or t h e st u d y if  a v ail a bl e. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   4 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1 1 .   R ef e r e n c e s 
 
1.    Br a g a  -  B as ari a   M,   D o bs   A S,   M ull er   D  C  et  al. M et a b oli c s y n dr o  m e i n   m e n   wit h   pr ost at e 
c a n c er  u n d er g oi n g l o n g- t er  m  a n dr o g e n- d e pri v ati o n t h er a p y. J o ur n al   Cli n   O n c ol  2 0 0 6; 
2 4( 2 4):  3 9 7 9- 3 9 8 3. 
2.    B as ari a  S,   M ull er   D  C,   C ar d u c ci   M  A,  et  al.   H y p er gl y c e  mi a  a n d i ns uli n r esist a n c e i n   m e n   wit h 
pr ost at e  c ar ci n o  m a   w h o r e c ei v e  a n dr o g e n  d e pri v ati o n t h er a p y.   C a n c er  2 0 0 6;  1 0 6( 3): 5 8 1- 5 8 8. 
3.    D o c k er y  F,   B ul pitt   CJ,   A g ar  w al  S,  et  al.  T est ost er o n e s u p pr essi o n i n   m e n   wit h  pr ost at e 
c a n c er l e a ds t o  a n i n cr e as e i n  art eri al stiff n ess  a n d  h y p eri ns uli n a e  mi a.   Cli n  S ci ( L o n d)  2 0 0 3; 
1 0 4: 1 9 5- 2 0 1. 
4.    S  mit h J  C,   B e n n ett  S,  E v a ns  L  M,  et  al.  T h e  eff e cts  of i n d u c e d  h y p o g o n a dis  m  o n  art eri al 
stiff n ess,  b o d y  c o  m p ositi o n,  a n d   m et a b oli c  p ar a  m et ers i n   m al es   wit h  pr ost at e  c a n c er. J   Cli n 
E n d o cri n ol   M et a b  2 0 0 1;  8 6( 9): 4 2 6 1- 4 2 6 7. 
5.    S  mit h   M  R,  Fi n k elst ei n J S,   M c  G o v er n  FJ,  et  al.  C h a n g es i n  b o d y  c o  m p ositi o n  d uri n g 
a n dr o g e n  d e pri v ati o n t h er a p y f or  pr ost at e  c a n c er. J   Cli n  E n d o cri n ol   M et a b  2 0 0 2;  8 7( 2): 5 9 9-
6 0 3. 
6.    S  mit h   M  R,  L e e   H,   N at h a n   D  M. I ns uli n s e nsiti vit y  d uri n g  c o  m bi n e d  a n dr o g e n  bl o c k a d e f or 
pr ost at e  c a n c er. J   Cli n  E n d o cri n ol   M et a b  2 0 0 6;  9 1( 4): 1 3 0 5- 1 3 0 8. 
7.    K e ati n g   N L,   O’  M all e y J,  S  mit h   M  R.   Di a b et es  a n d  c ar di o v as c ul ar  dis e as e  d uri n g  a n dr o g e n 
d e pri v ati o n t h er a p y f or  pr ost at e  c a n c er. J o ur n al  of   Cli ni c al   O n c ol o g y  2 0 0 6;  2 4( 2 7): 4 4 4 8-
4 4 5 6. 
8.    L e br et  T,   C ol o b y  P,   D es c ot es J L,  et  al.  E d u c ati o n al t o ol- kit  o n  di et  a n d  e x er cis e: s ur v e y  of 
pr ost at e  c a n c er  p ati e nts  a b o ut t o r e c ei v e  a n dr o g e n  d e pri v ati o n t h er a p y. J  of   Ur ol o g y 
2 0 1 0; 7 6: 1 4 3 4- 1 4 3 9.  
9.    K a h e n d e J  W,  L o o  mis   B  R,   A d hi k ari   B,  a n d   M ars h all  L.   A r e vi e  w  of  e c o n o  mi c  e v al u ati o ns  of 
t o b a c c o  c o ntr ol  pr o gr a  ms. I nt er n ati o n al J  of  E n vir o n  m e nt al   R es e ar c h  a n d  P u bli c   H e alt h 
2 0 0 9;  6: 5 1- 6 8.  
1 0.  N o hl ert  E,   H el g as o n   A  R,  Till gr e n  P,  et  al.   C o  m p aris o n  of t h e  c ost-  eff e cti v e n ess  of  a  hi g h - 
a n d  a l o  w-i nt e nsit y s  m o ki n g  c ess ati o n i nt er v e nti o n i n  S  w e d e n:  a r a n d o  mi z e d tri al.   Ni c oti n e 
a n d  T o b a c c o   R es e ar c h [ a c c e pt e d f or  p u bli c ati o n  2 0 1 3]. 
1 1.  T at e   D F, J a c k v o n y  E  H,   Wi n g   R  R.   A r a n d o  mi z e d tri al  c o  m p ari n g  h u  m a n  e-  m ail  c o u ns eli n g, 
c o  m p ut er- a ut o  m at e d t ail or e d  c o u ns eli n g,  a n d  n o  c o u ns eli n g i n  a n i nt er n et   w ei g ht l oss 
pr o gr a  m.   Ar c hi v es  of I nt er n al   M e di ci n e  2 0 0 6; 1 6 6( 1 5): 1 6 2 0- 2 5.  
1 2.  C h e u n g   A S,  P attis o n   D,   Br et h ert o n I,  et  al.   C ar di o v as c ul ar ris k  a n d  b o n e l oss i n   m e n 
u n d er g oi n g  a n dr o g e n  d e pri v ati o n t h er a p y f or  n o n- m et ast ati c  pr ost at e  c a n c er: i  m pl e  m e nt ati o n 
of st a n d ar di z e d   m a n a g e  m e nt  g ui d eli n es.   A n dr ol o g y  2 0 1 3; 1: 5 8 3- 5 8 9. 
1 3.  S  mit h   M  R.   C h a n g es i n f at  a n d l e a n  b o d y   m ass  d uri n g  a n dr o g e n- d e pri v ati o n t h er a p y f or 
pr ost at e  c a n c er. J  of   Ur ol o g y  2 0 0 4; 6 3( 4): 7 4 2- 7 4 5. 
1 4.  J e ns k y- S q uir es   N E,   Di eli-  C o n  wri g ht   C  M,   R oss u ell o   A,  et  al.   V ali dit y  a n d r eli a bilit y  of  b o d y 
c o  m p ositi o n  a n al ys ers i n  c hil dr e n  a n d  a d ults.   Br J  of   N utriti o n  2 0 0 8; 1 0 0( 4): 8 5 9- 8 6 5. 
1 5.  S  mit h   M  R,  L e e   H,   M c  G o v er n  F,  et  al.   M et a b oli c  c h a n g es  d uri n g  g o n a d otr o pi n- r el e asi n g 
h or  m o n e  a g o nist t h er a p y f or  pr ost at e  c a n c er.   C a n c er  2 0 0 8; 1 1 2: 2 1 8 8- 9 4. 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
1 6.  I nt e nsi v e  bl o o d- gl u c os e  c o ntr ol   wit h s ul p h o n yl ur e as  or i ns uli n  c o  m p ar e d   wit h  c o n v e nti o n al 
tr e at  m e nt  a n d ris k  of  c o  m pli c ati o ns i n  p ati e nts   wit h t y p e  2  di a b et es (  U  K P  D S  3 3).   U  K 
Pr os p e cti v e   Di a b et es  St u d y (  U  K P  D S)   Gr o u p.  L a n c et  1 9 9 8; 3 5 2( 9 1 3 1): 8 3 7. 
1 7.  B o n or a  E,  F or  m e nti ni   G,   C al c at err a  F,  et  al.   H  O  M  A-  esti  m at e d i ns uli n r esist a n c e is  a n 
i n d e p e n d e nt  pr e di ct or  of  c ar di o v as c ul ar  dis e as e i n t y p e  2  di a b eti c s u bj e cts:  pr os p e cti v e  d at a 
fr o  m t h e   V er o n a   Di a b et es   C o  m pli c ati o ns  St u d y.   Di a b et es   C ar e  2 0 0 2; 2 5: 1 1 3 5- 1 1 4 1. 
1 8.  S  mit h   M  R,   G o o d e   M,  Zi et  m a n   A L,  et  al.   Bi c al ut a  mi d e   m o n ot h er a p y  v ers us l e u pr oli d e 
m o n ot h er a p y f or  pr ost at e  c a n c er:  eff e cts  o n  b o n e   mi n er al  d e nsit y  a n d  b o d y  c o  m p ositi o n. J 
Cli n   O n c ol  2 0 0 4; 2 2( 1 3): 2 5 4 6- 2 5 5 3. 
1 9.  S h a hi ni a n   V  B,   K u o   Y F,  Fr e e  m a n J L,  a n d   G o o d  wi n J S.   Ris k  of fr a ct ur e  aft er  a n dr o g e n 
d e pri v ati o n f or  pr ost at e  c a n c er.   N e  w  E n gl J  of   M e di ci n e  2 0 0 5;  3 5 2( 2): 1 5 4- 1 6 4. 
2 0.  W ar e J E  a n d  S h er b o ur n e   C  D.  T h e   M  O S  3 6-  it e  m s h ort-f or  m  h e alt h s ur v e y ( S F- 3 6).   M e di c al 
C ar e  1 9 9 2; 3 0( 6): 4 7 3- 4 8 3. 
2 1.  P ot os k y   A L,   K n o pf   K,   Cl e g g  L  X,  et  al.   Q u alit y- of-lif e  o ut c o  m es  aft er  pri  m ar y  a n dr o g e n 
d e pri v ati o n t h er a p y: r es ults fr o  m t h e  Pr ost at e   C a n c er   O ut c o  m es  St u d y. J   Cli n   O n c ol  2 0 0 1; 
1 9( 1 7): 3 7 5 0- 3 7 5 7. 
2 2.  C ar p e nt er J S.  T h e  h ot fl as h r el at e d  d ail y i nt erf er e n c e s c al e. J  of  P ai n  a n d  S y  m pt o  m 
M a n a g e  m e nt  2 0 0 1; 2 2( 6): 9 7 9- 9 8 9. 
2 3.  S z y  m a ns ki   K  M,   W ei J T,   D u n n   R L,  a n d  S a n d a   M  G.   D e v el o p  m e nt  a n d  v ali d ati o n  of  a n 
a b br e vi at e d  v ersi o n  of t h e  E x p a n d e d  Pr ost at e   C a n c er I n d e x  c o  m p osit e i nstr u  m e nt f or 
m e as uri n g  h e alt h  -r el at e d  q u alit y  of lif e  a  m o n g  pr ost at e  c a n c er s ur vi v ors. J   Ur ol o g y 
2 0 1 0; 7 6( 5): 1 2 4 5- 1 2 5 0. 
2 4.  L e e   K  A,   Hi c ks   G,  a n d   Ni n o- M ur ci a   G.   V ali dit y  a n d r eli a bilit y  of  a s c al e t o  ass ess f ati g u e. 
Ps y c hi atr y   R es e ar c h  1 9 9 1; 3 6: 2 9 1- 2 9 8.  
2 5.  Pirl   W F,  Si e g el   GI,   G o o d e   MJ,  a n d  S  mit h   M  R.   D e pr essi o n i n   m e n r e c ei vi n g  a n dr o g e n 
d e pri v ati o n t h er a p y f or  pr ost at e  c a n c er:  a  pil ot st u d y.  Ps y c h o- O n c ol o g  y  2 0 0 2; 1 1: 5 1 8- 5 2 3. 
2 6.  Ji n   Y,   H a y es   D F,  Li  L,  et  al.  Estr o g e n r e c e pt or  g e n ot y p es i nfl u e n c e  h ot f l as h pr e v al e n c e  a n d 
c o  m p osit e s c or e  b ef or e  a n d  a ft er t a  m o xif e n th er a p y . J   Cli n   O n c ol  2 0 0 8; 2 6( 3 6): 5 8 4 9- 5 8 5 4. 
2 7.  R oss   R,   O h   W  K,   Xi e   W,  et  al. I n h erit e d  v ari ati o n i n t h e  a n dr o g e n  p at h  w a y is  a  ss o ci at e d wit h 
t h e  effi c a c y  of  a n dr o g e n  d e pri v ati o n t h er a p y i n   me n  wit h  pr ost at e  c  a n c er . J   Cli n   O n c ol 
2 0 0 8; 2 6( 6): 8 4 2- 4 7. 
2 8.  S a yl or  PJ,   K ar ol y  E  D,  S  mit h   M  R.  Pr os p e cti v e st u d y  of  c h a n g es i n t h e   m et a b ol o  mi c  pr ofil es 
of   m e n  d uri n g t h eir first  t hr e e   m o nt hs  of  a n dr o g e n  d e pri v ati o n t h er a p y f or  pr ost at e  c a n c er. 
Cli n   C a n c er   R es  2 0 1 2; 1 8: 3 6 7 7- 8 5. 
2 9.  M o a z z a  mi   A  A,  Z h a n g J  X,   K a  m al  -El di n  A,  et  al.   N u cl e ar   m a g n eti c r es o n a n c e  -b as e d 
m et a b ol o  mi cs  e n a bl e  d et e cti o n  of t h e  eff e cts  of  a   w h ol e  gr ai n r y e  a n d r y e  br a n  di et  o n t h e 
m et a b oli c  pr ofil e  of  pl as  m a i n  pr ost at e  c a n c er  p ati e nts. J   N utr  2 0 1 1; 1 4 1: 2 1 2 6- 3 2. 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x  1.   S el e ct e d   G e n eti c  P ol y  m o r p hi s  m s  
 
G e n e  
P ol y  m o r p his  m   
L o c ati o n     
P r ot ei n   
R ef e r e n c e 
C  Y P 1 9  A 1  
( T T T  A)n     
I ntr o n  4   
Ar o  m at as e   
Ts u c hi y a   N,  et  al J  of 
Cli n   O n c ol  2 0 0 6   
C  Y P 1 9  A 1   
rs 1 8 7 0 0 5 0   A >  C   
5  k b  u pstr e a  m   
Ar o  m at as e   
R oss   R,  et  al J  of   Cli n 
O n c ol  2 0 0 8   
H S  D 3  B 1   
rs 1 8 5 6 8 8 8   A >  G   
1 3  k b  u pstr e a  m   
H S  D   
R oss   R,  et  al J  of   Cli n 
O n c ol  2 0 0 8   
H S  D 1 7  B 4 
rs 7 7 3 7 1 8 1   C >  G   
I ntr o n   
H S  D   
R oss   R,  et  al. J  of 
Cli n   O n c ol  2 0 0 8   
S  L  C  O 1  B 3  
3 3 4  T >  G 
E x o n  3   
O  A T P   
H a  m a d a   A,  et  al.   Cli n 
C a n c er   R es  2 0 0 8   
S  L  C  O 1  B 3  
6 9 9   G >  A 
E x o n  6   
O  A T P   
H a  m a d a   A,  et  al.   Cli n 
C a n c er   R es  2 0 0 8   
S  L  C  O 2  B 1  
rs 1 2 4 2 2 1 4 9   A >  G   
E x o n  7   
O  A T P   
Y a n g   M,  et  al. J  of 
Cli n   O n c ol  2 0 1 1   
S  L  C  O 2  B 1  
rs 1 7 8 9 6 9 3   
I ntr o n  7   
O  A T P   
Y a n g   M,  et  al. J  of 
Cli n   O n c ol  2 0 1 1   
S  L  C  O 2  B 1  
rs 1 0 7 7 8 5 8   
I ntr o n  8   
O  A T P   
Y a n g   M,  et  al. J  of 
Cli n   O n c ol  2 0 1 1   
A  R   
(  C  A  G)n 
E x o n  1 (  N T  D) 
A n dr o g e n 
R e c e pt or   
St a nf or d J,  et  al. 
C a n c er   R es  1 9 9 7   
A  R   
(  G  G  C)n   
E x o n  1 (  N T  D) 
A n dr o g e n 
R e c e pt or   
St a nf or d J,  et  al. 
C a n c er   R es  1 9 9 7   
A  R   
rs 1 7 3 0 2 0 9 0   
Pr o  m ot er 
A n dr o g e n 
R e c e pt or   
Li n dstr o  m  et  al   Cli n 
C a n c er   R es  2 0 0 7   
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x   2 . Q u alit y  of  Lif e   Q u e sti o n n ai r e s  
S F - 1 2  ®: 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
E PI  C  - 2 6: 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
L e e  F ati g u e  S c al e:   
 
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   5 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 0  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
Att e nti o n al  F u n cti o n al I n d e x   
 
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 1  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
E x e r cis e  P att e r n   Ass ess  m e nt   (  B as eli n e): 
 
 
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 2  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 3  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
                             F  O  O  D  A  N  D   B  E  V  E  R  A  G  E   W  O  R  K S  H  E  E  T      
   
                
N a  m e:  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Bi rt h d at e:    _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
D a y  of t h e   W e e k:  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
   Pl e as e r e c or d  all f o o ds   &  b e v er a g es  c o ns u  m e d f or t h e  d a y -  t h e   m or e  d et ail e d t h e r e c or d, t h e 
m or e  a c c ur at e t h e  a n al ysis   will  b e.  F or  e x a  m pl e: t ur k e y s a n d  wi c h ( 2 sli c es   w h ol e   w h e at   br e a d,  3 
o z t ur k e y,   ½  c u p l ett u c e,   ¼  c u p t o  m at o,  1 t bs p   m ust ar d). I n cl u d e t  w o   w e e k  d a ys   &  o n e   w e e k e n d 
d a y.  
Ti  m e   
F o o d  o r   B e v e r a g e  
A  m o u nt   
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
   
 
 
W as t his  d a y t y pi c al ?        
   
  Y es       
  N o   
If  n ot,  h o  w s o ? 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 4  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
 
E  Q  - 8   Q u oti e nt 
 
Pl e as e  a ns  w e r  o n  a s c al e  of  1 -5 ( 1  dis a g r e e st r o n gl y;  5  a g r e e  c o  m pl et el y)  h o  w   w ell  e a c h 
st at e  m e nt   m at c h es  y o u r  p e rs o n alit y: 
 
1. I fi n d it  e as y t o  p ut   m ys elf i n s o  m e b o d y  els e’s s h o es. 
 
2. I  a  m  g o o d  at  pr e di cti n g  h o  w  s o  m e o n e   will f e el.  
 
3. I  a  m  q ui c k t o s p ot   w h e n s o  m e o n e i n  a  gr o u p is f e eli n g  a  w k  w ar d  or  u n c o  mf ort a bl e. 
 
4.   Ot h er  p e o pl e t ell   m e I  a  m  g o o d  at  u n d erst a n di n g  h o  w t h e y  ar e f e eli n g  a n d   w h at t h e y  ar e 
t hi n ki n g. 
 
5. I fi n d it  h ar d t o  k n o  w   w h at t o  d o i n  a s o ci al sit u ati o n. 
 
6. I  oft e n fi n d it  h ar d t o j u d g e if s o  m et hi n g is r u d e  or  p olit e. 
 
7. It is  h ar d f or   m e t o s e e   w h y s o  m e t hi n gs  u ps et  p e o pl e s o   m u c h. 
 
8.   Ot h er  p e o pl e  oft e n s a y t h at I  a  m i ns e nsiti v e, t h o u g h I  d o n’t  al  w a ys s e e   w h y. 
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 5  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x  3.  C h a rl s o n  C o  -M o r bi d  it y I n d e x 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 6  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x  4  :   Bi o el e ct ri c al I  m p e d a n c e   D e vi c e f o r   A s s e s s  m e nt  of 
P e r c e nt a g e   B o d y  F at  
 
 
 
I  m p e di  M e d   D F 5 0  
 
I nst r u cti o n   M a n u al   Li n k:  
 
htt p://  w  w  w.i  m p e di  m e d. c o  m/ pr o d u cts/ df 5 0/ df 5 0-f or- us a. ht  m  
 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 7  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x  5:   A c c el e r o  m et e r  F o r   A  m b ul at o r y   R e c o r di n g  of  A cti vit y  L e v el s   
 
 
A cti g r a p h   G  T 3  X +   A c c el e r o  m et e r   
 
 
A c c el er o  m et er  P arti ci p a nt I nstr u cti o ns   
-   Pl e as e   w e ar t h e  b elt   wit h t h e  a c c el er o  m et er f or s e v e n  d a ys, st arti n g t h e   m or ni n g  of 
_ _ _ _ _ _ _ _ _ _ _  a n d  e n di n g t h e  e v e ni n g  of _ _ _ _ _ _ _ _ _ _ _ _ _ _ _. 
-   W e ar   t h e  b elt  ar o u n d  y o ur   w aist   wit h t h e  a c c el er o  m et er  pl a c e d  o n  y o ur ri g ht si d e.  T h e 
d e vi c e s h o ul d  b e  att a c h e d s e c ur el y t o  y o ur  b o d y s o it  d o es  n ot  h a v e  a n y  e xtr a n e o us 
m o v e  m e nt. 
-   Pl e as e   w e ar t h e  b elt   wit h t h e  a c c el er o  m et er  at  all ti  m es   w h e n  a  w a k e, fr o  m risi n g  i n t h e 
m or ni n g  u ntil  g oi n g t o sl e e p  at  ni g ht, f or s e v e n  c o ns e c uti v e  d a ys. 
-   T h e  d e vi c e is  N  O  T     w at er pr o of  – r e  m o v e t h e  b elt   w h e n  b at hi n g  or s  wi  m  mi n g. 
-   Pl e as e r et ur n t h e  b elt   wit h t h e  a c c el er o  m et er  i n  p ers o n,  or  vi a   U S P S i n t h e  pr o vi d e d 
a d dr ess e d st a  m p e d  e n v el o p e,  as s o o n  as  p ossi bl e  aft er  c o  m pl eti n g  y o ur s e v e n  d a ys. 
-   If  a n y  q u esti o ns,  pl e as e  c o nt a ct  us  vi a  e  m ail  or t el e p h o n e:  E v el y n   H a n g 
at  H a n g E  @ c c. u csf. e d u    or  4 1 5- 8 8 5- 3 3 5 7. 
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 8  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x   6 .  D at a  a n d  S af et y   M o nit o ri n g   Pl a n  f o r  a P h a s e  2 I n stit uti o n al 
St u d y  
 
T h e   U  C  S F   H el e n   Dill er  F a  mil y   C o  m pr e h e n si v e   C a n c er   C e nt er (  H  D F  C  C  C)   D at a  a n d   S af et y 
M o nit ori n g   C o  m  mitt e e (  D S  M  C) i s r e s p o n si bl e f or   m o nit ori n g  d at a  q u alit y  a n d  s u bj e ct  s af et y f or 
all   H  D F  C  C  C i n stit uti o n al  cli ni c al  st u di e s.   A  s u  m  m ar y  of   D  S  M  C  a cti viti e s f or t hi s  st u d y i n cl u d e:    
•    R e vi e  w  of   Gr a d e  2  a n d  hi g h er  a d v er s e  e v e nt s.   
•    R e vi e  w  of  s u s p e ct e d  a d v er s e r e a cti o n s  c o n si d er e d “ s eri o u s”  . 
M o nit ori n g  a n d   R e p orti n g   G ui d eli n e s   
I n v e sti g at or s   will  c o n d u ct  c o nti n u o u s r e vi e  w  of  d at a  a n d  s u bj e ct  s af et y  a n d  di s c u s s  e a c h 
s u bj e ct’ s tr e at  m e nt  at   m o nt hl y   Sit e   C o  m  mitt e e   m e eti n g s.  T h e s e  di s c u s si o n s  ar e  d o c u  m e nt e d i n 
t h e   Sit e   C o  m  mitt e e   m e eti n g   mi n ut e s.  T h e  di s c u s si o n   will i n cl u d e t h e  n u  m b er  of  s u bj e ct s, 
si g nifi c a nt t o xi citi e s i n  a c c or d a n c e   wit h t h e  pr ot o c ol,  a n d  o b s er v e d r e s p o n s e s.  
A d v er s e   E v e nt   R e vi e  w  a n d   M o nit ori n g   
All  gr a d e( s)  3  -5  a d v er s e  e v e nt s,   w h et h er  or  n ot  u n e x p e ct e d,  a n d   w h et h er  or  n ot  c o n si d er e d t o 
b e  a s s o ci at e d   wit h t h e  u s e  of t h e  st u d y  tr e at  m e nt,   will  b e  e nt er e d i nt o   O n  C or e  ®,   U  C  S F’ s 
Cli ni c al  Tri al   M a n a g e  m e nt   S y st e  m.   
All  gr a d e( s)  3  -5  a d v er s e  e v e nt s  e nt er e d i nt o   O n  C or e  ®   will  b e r e vi e  w e d  o n  a   m o nt hl y  b a si s  at 
t h e   Sit e   C o  m  mitt e e   m e eti n g s.  T h e   Sit e   C o  m  mitt e e   will r e vi e  w  a n d  di s c u s s t h e  s el e ct e d t o xi cit y, 
t h e t o xi cit y  gr a d e,  a n d t h e  attri b uti o n  of r el ati o n s hi p  of t h e  a d v er s e  e v e nt t o t h e  a d  mi ni str ati o n  of 
t h e  st u d y tr e at  m e nt. 
I n  a d diti o n,  all  s u s p e ct e d  a d v er s e r e a cti o n s  c o n si d er e d “ s eri o u s”  e nt er e d i nt o   O n  C or e  ®,   will  b e 
r e vi e  w e d  a n d   m o nit or e d  b y t h e   D at a  a n d   S af et y   M o nit ori n g   C o  m  mitt e e  o n  a n o n g oi n g  b a si s  a n d 
di s c u s s e d  at   D  S  M  C   m e eti n g s,   w hi c h t a k e  pl a c e  e v er y  si x   w e e k s.  
If  a  d e at h  o c c ur s  d uri n g t h e tr e at  m e nt  p h a s e  of t h e  st u d y  or   wit hi n  3 0  d a y s  aft er t h e l a st 
a d  mi ni str ati o n  of t h e  st u d y  tr e at  m e nt a n d it i s  d et er  mi n e d t o  b e r el at e d  eit h er t o t h e  st u d y 
tr e at  m e nt or t o  a  st u d y  pr o c e d ur e, t h e I n v e sti g at or  or  hi s/ h er  d e si g n e e   m u st  n otif y t h e  D  S  M  C 
C h air   wit hi n   1  b u si n e s s  d a y  of  k n o  wl e d g e  of t hi s  e v e nt.  T h e  c o nt a ct   m a y  b e  b y  p h o n e  or  e -
m ail.  
I n cr e a s e i n   A d v er s e   E v e nt   R at e s 
If  a n i n cr e a s e i n t h e fr e q u e n c y  of   Gr a d e  3  or  4  a d v er s e  e v e nt s ( a b o v e t h e r at e r e p ort e d i n t h e 
I n v e sti g at or   Br o c h ur e  or  p a c k a g e i n s ert) i s  n ot e d i n t h e  st u d y,  a r e p ort  s h o ul d  b e  s u b  mitt e d t o 
t h e   D  S  M  C  at t h e ti  m e t h e i n cr e a s e d r at e i s i d e ntifi e d.  T h e r e p ort   will i n di c at e if t h e i n ci d e n c e  of 
a d v er s e  e v e nt s  o b s er v e d i n t h e  st u d y i s  a b o v e t h e r a n g e  st at e d i n t h e I n v e sti g at or   Br o c h ur e  or 
p a c k a g e i n s ert.  
If  at  a n y ti  m e t h e I n v e sti g at or  st o p s  e nr oll  m e nt  or  st o p s t h e  st u d y  d u e t o  s af et y i s s u e s, t h e 
D  S  M  C   C h air  a n d   D  S  M  C   M a n a g er   m u st  b e  n otifi e d   wit hi n  1  b u si n e s s  d a y  vi a  e  -m ail.  T h e   D  S  M  C 
m u st r e c ei v e  a f or  m al l ett er   wit hi n  1 0  b u si n e s s  d a y s  a n d t h e   C  H  R   m u st  b e  n otifi e d  . 
D at a  a n d   S af et y   M o nit ori n g   C o  m  mitt e e   C o nt a ct s:   
D  S  M  C   C h air:    
 
D  S  M  C   M o nit or s    
P h o n e:    
E  m ail:   
A d dr e s s:    
 
 
 
U  C  S F   H el e n   Dill er  F a  mil y 
C o  m pr e h e n si v e   C a n c er   C e nt er   
S a n  Fr a n ci s c o,   C  A  9 4 1 1 5   
*   D S  M P    a p pr o v e d  b y   N  CI  0 9/ F e br u ar y 2 0 1 2 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   6 9  O F   7 0  


V ersi o n  d at e:  0 7  -0 7 -2 0 1 5                                                                                                                Pr ot o c ol   C  C #  1 3 5 5 1 3  
A p p e n di x   7.  S p e ci  m e n  H  a n dli n g  a n d  St o r a g e  
 
At  b as eli n e,   f or  p ati e nts   w h o  a gr e e t o  p arti ci p at e i n t his  o pti o n al  c o  m p o n e nt  of t h e  st u d y, a  1 2 -
m L  bl o o d  s a  m pl e  i n   t  w o  pl asti c   E  D T  A  t u b es will  b e   c oll e ct e d  fr o  m  e a c h  p arti ci p a nt.  S a  m pl es  
will   b e    st or e d  i n   a  8 0   d e gr e es   b el o  w   C elsi us    fr e e z er  i n  t h e    U  C S F    H el e n    Dill er   F a  mil y 
C o  m pr e h e nsi v e   C a n c er   C e nt er  .   G e n o  mi c D  N  A   will  b e   e xtr a ct e d  b y  usi n g  a   QI  A  m p   D  N  A   Mi ni 
Kit  (
) a c c or di n g t o t h e   U  C S F   D  N  A   B a n k  st a n d ar d  o p er ati n g  pr o c e d ur es . 
B at c h e d   D  N  A  s a  m pl es   will  b e t a k e n   t o t h e   Kr o et z l a b or at or y  at   U  C S F   Missi o n   B a y  c a  m p us f or 
p ol y  m or p his  m  ass ess  m e nt.  
 
I n  a d diti o n,  at  b as eli n e  a n d  aft er  e v er y  3   m o nt hs  o n  st u d y,  a n d  at  6   m o nt hs f oll o  wi n g  c o  m pl eti o n 
of  S T  A  N  D  cli ni c  p arti ci p ati o n,  2 0   m L  of   w h ol e  bl o o d   will  b e  c oll e ct e d i n  o n e ti g ert o p  (s er u  m) 
a n d  o n e l a v e n d er t o p t u b e ( pl as  m a)  a n d  c e ntrif u g e d  at  3 0 0 0 r p  m f or  1 0   mi n ut es.   T h e  s er u  m  a n d 
pl as  m a   will  b e  d e c a nt e d  i nt o  t  w o  2 -m L  p ol y pr o p yl e n e  s cr e  w  c a p  (l e a k  -pr o of)  vi als  (f o ur  t ot al 
vi als)  t h at  h a v e  b e e n  pr o p erl y  l a b el e d   wit h  t h e  u ni q u e  s p e ci  m e n  l o g  n u  m b er  a n d  st or e d  at   - 8 0 
d e gr e es   C elsi us.   
 
S a  m pl es   will  b e  c at al o g u e d i n di vi d u all y i n  p ass  w or d  pr ot e ct e d tiss u e  d at a b as e.  P ati e nt i d e ntifi ers 
will  b e  r e  m o v e d  fr o  m  t his  d at a b as e  a n d  s u bstit ut e d    wit h  st u d y  I  D  n u  m b ers.    A n n ot ati o ns  f or 
i n di vi d u al tiss u e/ bl o o d s a  m pl es   will  b e   m a d e f or  pr o c essi n g.    
 
 
P h a s e  2  –  S T A  N  D  Cli ni c  
P  A  G  E   7 0  O F   7 0  

ICF_001.pdf: 
IRB NUMBER: 14-13335
IRB APPROVAL DATE: 03/08/2018
IRB EXPIRATION DATE: 03/07/2019
ICF 12-20-2016
PAGE 1 OF 15
CC# 135513
Protocol version #3.0 (07-07-2015)
 Rahul Aggarwal, MD
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
CONSENT TO PARTICIPATE IN A RESEARCH STUDY
CC#:  135513  A Multidisciplinary Team-Based Approach to Mitigate the Impact of 
Androgen Deprivation Therapy in Prostate Cancer: a Randomized Phase 2 Study.
The “STAND” (Supportive Therapy in Androgen Deprivation) Clinic
This is a clinical trial, a type of research study. Your study doctor, Rahul Aggarwal M.D., 
and his associates from the University of California, San Francisco (UCSF), Division of 
Hematology/Oncology, Department of Medicine, will explain the clinical trial to you. 
Clinical trials include only people who choose to take part. Please take your time to 
make your decision about participating. You may discuss your decision with your family 
and friends and with your health care team. If you have any questions, you may ask 
your study doctor. 
You are being asked to take part in this study because you have prostate cancer and 
are a candidate for, or have started, androgen deprivation therapy (ADT; ie. hormone 
therapy) for your cancer.
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to determine how to best improve health outcomes and 
manage the potential side effects of hormone therapy. Side effects of hormone therapy 
include hot flashes, fatigue, decreased interest in sex, loss of bone density, weight gain, 
and mood changes, among others. Our current approach to address these issues is to 
evaluate patients in clinic every 3 months, perform counseling and education during the 
course of the visit, and if necessary, refer patients to exercise, nutrition, and/or symptom 
management services. 
The STAND clinic was created to offer a structured approach for men receiving 
hormone therapy. Clinic participation consists of monthly visits with Nutrition, Exercise, 
and Symptom Management services on a rotating basis, as well as self-directed patient 
education sessions. 
It is not known whether participation in a structured program such as the STAND clinic, 
versus the current approach outlined above, leads to better outcomes with respect to 
potential side effects of hormone therapy. This study is being done to compare these 
two approaches and help decide which is better in improving the following factors: 
changes in your percentage body fat and factors that affect your metabolism, your bone 
health, and your quality of life.
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?
Up to 100 people may participate in the study at UCSF.
NCT# 02168062


IRB NUMBER: 14-13335
IRB APPROVAL DATE: 03/08/2018
IRB EXPIRATION DATE: 03/07/2019
ICF 12-20-2016
PAGE 2 OF 15
CC# 135513
Protocol version #3.0 (07-07-2015)
 Rahul Aggarwal, MD
WHAT WILL HAPPEN IF I TAKE PART IN THIS RESEARCH STUDY?
Participants in this study who are not receiving current chemotherapy will be 
randomized into 1 of 2 groups. Randomization means that you are put into a group by 
chance (like rolling dice). A computer program will place you in one of the groups. 
Neither you nor your doctor can choose the group you will be in. You will have an equal 
(one in two) chance of being placed in any group.
If you are placed in group 1 (standard of care treatment), you will have clinic visits every 
3 months and receive current standard of care therapy outlined above. During the visits 
there will be:

A review of your medical history and current medications

Assessment of the impact of hormone therapy on body composition and certain
laboratory tests (e.g. fasting cholesterol levels)

Toxicity assessment

Lifestyle modification counseling and review of quality of life and side effects of
androgen deprivation therapy (ADT; ie. hormone therapy) with questionnaires by 
a trained nurse practitioner and/or physician. Quality of life questionnaires cover 
various items including your mood, energy level, severity of hot flashes, and 
overall functional level. The questionnaires will take approximately 20-30 minutes 
to complete, and can be completed electronically prior to your visit or on paper 
during the course of your visit. The PHQ-9 questionnaire screening for 
depression will be completed in person during your study visit. 

Medication management including hormone injections

Referrals to exercise, nutrition and symptom management services upon patient
request or if deemed necessary by your health care provider. You will have the 
option of visiting with each of these services as many times as necessary during 
the course of the study. 
After 12 months on study, patients in group 1 will have the opportunity to participate 
in the STAND clinic for the next 12 months or for the duration of their hormone 
therapy treatment.
If you are placed in group 2 (STAND clinic), in addition to visits with your health care 
provider every 3 months and assessments as outlined above, you will participate in the 
STAND clinic. The STAND clinic consists of monthly clinic visits in which you will see 
the following services on a rotating basis: 

Nutrition counseling

Exercise training

Symptom management by trained physician and/or nurse practitioner


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In addition, every month you will view an education “module” during your visit, 
consisting of Powerpoint slide presentations covering the various aspects of hormone 
therapy. 
All patients currently receiving or planning to receive chemotherapy will be placed into 
Group 2 (STAND clinic).
Before you begin the main part of the study...
You will need to have the following exams, tests or procedures to find out if you can be 
in the main part of the study. Some of these exams, tests or procedures are part of 
regular cancer care and may be done even if you do not join the study. You will also 
have some procedures that are only being done because you are in the study. These 
are listed as research procedures. If you have had some of them recently, they may not 
need to be repeated. This will be up to your study doctor. 
You must complete the following procedures within 6 weeks prior to day 1 of the study. 
Your visit may take about 1-2 hours.

Physical exam

Review of medical history and assessment of other medical conditions

Weight, body mass index.

Blood draw (about 2 tablespoons) for PSA, if not already receiving ADT.
Research Procedures:

Review of medications that you are taking

DXA Bone Density Scan: An imaging test that measures bone density (the 
amount of bone mineral contained in a certain volume of bone) by passing x-rays
with two different energy levels through
 is used to diagnose 
osteoporosis (decrease in bone mass and density). A bone density scan, using a 
central machine, takes about 15 minutes, including registration. During the 
procedure, you will lie on a table scanner for five to eight minutes. 

Measurement of exercise patterns:  Your physical activity will be measured using
an accelerometer.  This is a small plastic device (about 2 inches on each side) 
that is worn on an elastic waistband around your waist for 7 consecutive days.  It 
must be kept on at all times except when bathing or swimming (it is not 
waterproof).

Measurement of the ratio of the length of your 2nd and 4th digit of your right hand

Optional CT scan of the radius and tibia (long bones of the arm and leg)
During the main part of the study...
If the exams, tests and procedures show that you can be in the main part of the study, 


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and you choose to take part, then you will randomized with equal probability to one of 
the two study “arms” or groups (current standard of care or participation in the STAND 
clinic). 
Regardless of your assignment, you will also be placed into one of four strata 
(subgroups), taking into account the duration of hormone therapy prior to study entry 
and body mass index at study entry. 
All patients will have the following visits  
Day 1 (the visit will take about 1 hour)

Physical exam

Height, weight, body mass index, and percent body fat measurement

LHRH Analogue (hormone injection). If you have already started hormone
therapy, you will be kept on the same schedule as before and may not receive 
hormone injection on the day 1 study visit. Hormone therapy can include  Eligard, 
Zolodex, Trelstar, or Leuprolide Acetate; you and your doctor will discuss which 
brand you receive. There are no significant differences in treatment effect nor 
side effects between brands.

Blood (about 1-2 tablespoons) will be drawn for
o
Fasting lipid/glucose panel and insulin level
o
Hemoglobin A1c (to measure glucose levels)
o
Serum 25-(OH) vitamin D level
o
Serum PSA –a protein produced by the prostate gland, that is used to
monitor treatment response
o
Serum testosterone
You will need to fast for at least 10 hours prior to the blood draw.
Research Procedures:

Review of medications that you are taking

Questions about how your disease is affecting your daily life

Quality of life questionnaires

Questions about your nutritional habits.

Blood (about 1 tablespoon) will be drawn for:
o
Studying metabolism changes of your cells which may help researchers
understand how drug therapies and interventions may be working. 
o
Banking - the researchers would like to collect and store (bank) your blood
for future research. To protect your privacy, your blood samples will be 
identified by your subject number, not your name. These samples will be 
stored at UCSF indefinitely. The researchers and authorized members of 
this research study will have access to the samples and data collected. 
The samples will be destroyed when they are no longer needed.


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
Your blood will be used only for research and will not be sold. The
research done with your specimens may help to develop new
products in the future. You will not be paid for donating blood. If any
discoveries or commercial products are made as a result of
research done on your blood, neither you nor your family will
receive any financial benefits or compensation.
In the future, we may give your specimens and certain medical
information about you (for example, diagnosis, blood pressure, age
if less than 85) to other scientists or companies not at UCSF,
including to a government health research database, but we will not
give them your name, address, phone number, or any other
information that would identify you. Reports about any research will
not be given to you or your doctor.

Sometimes specimens are used for genetic research (about
diseases that are passed on in families). Even if we use the 
specimen for genetic research, we will not put the results in your 
medical record. The research will not change the care you receive. 
Your personal health information cannot be used for additional 
research without additional approval from either you or a review 
committee.
o
Optional blood collection to examine genetic changes. Please refer to
“Using Blood for Research” section at end of form.
The following will be done at the end of every 3 months (the visit will take about 1 
hour):

Physical exam

Weight, body mass index, and percent body fat measurement

LHRH analogue (hormone injection)

Referral to Nutrition, Exercise, and Symptom Management Services upon your
request or if deemed necessary by your health care provider 

Counseling with health care provider to discuss lifestyle modifications, review
laboratory results 

Blood (about 1-2 tablespoons) will be drawn for
o
Fasting lipid/glucose panel and insulin level
o
Hemoglobin A1c (to measure glucose levels)
o
Serum 25-(OH) vitamin D level
o
Serum PSA
You will need to fast for at least 10 hours prior to the blood draw.
Research Procedures:


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
Review of medications that you are taking

Questions about how your disease is affecting your daily life

Quality of life questionnaires

Measurement of exercise patterns (accelerometer) during month 6

Blood (about 1 tablespoon) will be drawn for:
o
To study metabolism changes of your cells
o
Banking
Patients in Group 2 (STAND clinic), will have the following additional, monthly 
visits.
During the course of these monthly visits, there will be a series of self-guided 
educational modules discussing various aspects of ADT and management of side 
effects. These modules will be a series of PowerPoint slides that you view during your 
visit. You will have the opportunity to ask questions before and after you view each 
module. These will also be available to all patients for review outside of the clinic. 
You will have individualized sessions with exercise physiologist, registered dietitian, and 
symptom management services. You will see one of these providers each month on a 
rotating basis for the 12 month duration of the clinic. In total, you will visit with each 
service four times during the course of the year. The STAND clinic visits will take about 
1-2 hours.
All patients will have the following end of the study visit (12 months):
You will have an end of treatment visit at approximately 12 months after beginning the 
study. The visit will take about 2 hours and the following tests and procedures will occur: 

Physical exam

Weight, body mass index, and percent body fat measurement

Counseling with health care provider to discuss lifestyle modifications, review
laboratory results 

Blood (about 1-2 tablespoons) will be drawn for
o
Fasting lipid panel/glucose and insulin level
o
Hemoglobin A1c (to measure glucose levels)
o
Serum 25-(OH) vitamin D levels
o
Serum PSA
o
Serum testosterone
You will need to fast for at least 10 hours prior to the blood draw.
Research Procedures:

Review of medications that you are taking

Questions about how your disease is affecting your daily life

Quality of life questionnaires


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
Questions about your nutritional habits

Measurement of exercise patterns (accelerometer)

DXA Bone Density Scan

Optional CT scan of the radius and tibia (long bones of the arm and leg)

Blood (about 1 tablespoon) will be drawn for
o
To study metabolism changes of your cells
o
Blood collection for banking
Follow Up Visits
If you are randomized to the group 1 (current standard-of-care study arm), you will have 
the option to participate in the STAND clinic after the end of study visit at 12 months. 
Patients who opt to participate in the STAND clinic will be followed for an additional 12 
months. The STAND clinic schedule will be identical to that followed by patients initially 
randomized to the STAND clinic. 
All patients who have completed the STAND clinic will be followed by telephone calls 
after 2 and 4 months to see how you are doing. At 6 months following completion of the 
STAND clinic, you will return for a clinic visit (the visit will take about 1 hour) and have 
the following procedures:

Physical exam

Weight, body mass index, and percent body fat measurement

Counseling with health care provider to discuss lifestyle modifications, review
laboratory results

Blood (about 1-2 tablespoons) for:
o
Fasting lipid panel/glucose and insulin level
o
Hemoglobin A1c
o
Serum PSA
o
Serum testosterone
You will need to fast for at least 10 hours prior to the blood draw.
Research Procedures:

Quality of life questionnaires

Blood (about 1 tablespoon) will be drawn for
o
To study metabolism changes of your cells
o
Banking
STUDY LOCATION: 
All study procedures will be done at the Helen Diller Family Comprehensive Center at 
UCSF. 


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HOW LONG WILL I BE IN THE STUDY?
Participants in the group 1 will receive standard of care treatment for 12 months and 
may choose to participate in the STAND clinic for up to 12 months. Participants in group 
2 will participate in the STAND clinic for 12 months. Participants in the STAND clinic will 
be followed for an additional 6 months after completion of the STAND clinic.
CAN I STOP BEING IN THE STUDY?
Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about 
stopping or decide to stop, and they will tell you how to stop safely. 
It is important to tell the study doctor if you are thinking about stopping, so that your 
doctor can talk about what follow-up care and testing could be most helpful for your 
cancer treatment.
The study doctor may stop you from taking part in this study at any time if they believe it 
is in your best interest, if you do not follow the study rules, or if the study is stopped.
WHAT SIDE EFFECTS OR RISKS CAN I EXPECT FROM BEING IN THE STUDY?
Risks and Side Effects Related LHRH analogs (Eligard, Zoladex, Lupron Depot or 
Trelstar):
Likely

Hot flashes

Fatigue

Mild breast enlargement and pain

Nipple tenderness

Decreased interest in sexual activity

Difficulty maintaining an erection

Decreased bone mineral density
Less Likely

Mood changes including depression

Nausea and vomiting

Swelling of your hands, feet and legs

Low blood counts, which may cause fatigue, shortness of breath when walking,
feeling more cold than usual

Injection site burning and/or stinging


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
Increased blood sugar levels

Increased cholesterol levels

Headaches
Rare but serious

Increased risk of diabetes

Increased risk of heart attacks or stroke
Risks related to Study Procedures 
Randomization Risks:  You will be assigned to a study arm by chance, and the 
treatment you receive may prove to be less effective than the other study.
Blood Drawing (venipuncture) risks: Drawing blood may cause temporary discomfort 
from the needle stick, bruising, and infection.
Bioelectrical Bioimpedance Device for Assessment of Body Fat risks: The weak 
electrical current used to
your body fat is not felt while using the monitor. Do 
not use, or allow others to use, this monitor if fitted with a cardiac pacemaker or other 
medical device. Pregnant women should not use this device
Quality of Life (QOL) Questionnaires risks:  
Answering the Quality of Life 
questionnaire may be an inconvenience. Some of the questions may remind you of 
unpleasant aspects of your therapy or disease, and you may experience some 
discomfort, anxiety or distress in answering such questions. You are free to decline to 
answer any questions you do not wish to answer, or to stop participating at any time.
Bone Mineral Density Scan (DXA) risks: The scanner uses beams of low energy 
radiation to determine the density of the bone or for soft tissue analysis. 
Radiation risks:  This research study involves exposure to radiation from two DXA  
Scans and two optional CT scans of the radius/tibia. This radiation exposure is not 
necessary for your medical care and is for research purposes only. The additional 
amount of radiation that you will receive as a result of participating in this study will be 
less than the yearly natural background radiation in the US, which is 3 mSv (a mSv, or 
milliSievert, is a measurement of radiation). This amount of radiation involves minimal 
risk. If you have any questions regarding the use of radiation or the risks involved, 
please consult the physician conducting the study.
Unknown risks: It is possible that unexpected side effects could occur or that the side 
effects could be more severe than anticipated. At this time, all the side effects of these 


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treatments are not known. Patients must report any unusual symptoms to their doctor 
immediately.
For more information about risks and side effects, ask your study doctor.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
Taking part in this study may or may not make your health better. While doctors hope 
that participation in the STAND clinic or seeing nutrition, exercise, and symptom 
management services on a referral basis will mitigate the side effects associated with 
ADT treatment, there is no proof of this. We do know that the information from this study 
will help doctors learn more about the management of side effects of ADT treatment. 
This information could help future cancer patients.
WHAT OTHER CHOICES DO I HAVE IF I DO NOT TAKE PART IN THIS STUDY?
Your other choices may include:

Getting treatment or care for your cancer without being in a study (i.e. hormone
therapy). 

Taking part in another study

Getting comfort care, also called palliative care - this type of care helps reduce
pain, tiredness, appetite problems and other problems caused by the cancer; 
comfort care does not treat the cancer directly, it works to improve how you feel 
and keep you as active and comfortable as possible

Getting no treatment
Your physician will discuss these other options with you. Please talk to your doctor 
about your choices before deciding if you will take part in this study.
WILL MY MEDICAL INFORMATION BE KEPT PRIVATE?
We will do our best to make sure that the personal information in your medical record is 
kept private. However, we cannot guarantee total privacy. Your personal information 
may be given out if required by law. If information from this study is published or 
presented at scientific meetings, your name and other personal information will not be 
used.
Organizations that may look at and/or copy your medical records for research, quality 
assurance, and data analysis include:

The National Cancer Institute (NCI) and other government agencies, e.g., the


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Food and Drug Administration (FDA), involved in overseeing research 

The University of California
Participation in research may involve a loss of privacy, but information about you will be 
handled as confidentially as possible. A medical record will be created because of your 
participation in this study. Your consent form and some of your research test results will 
be included in this record. Therefore, your other doctors may become aware of your 
participation. Hospital regulations require that all health care providers treat information 
in medical records confidentially.
WHAT ARE THE COSTS OF TAKING PART IN THE STUDY?
You and/or your health plan/insurance company will need to pay for some or all of the 
costs of treating your cancer in this study. Some health plans will not pay these costs for 
taking part in studies. Check with your health plan/insurance company to find out what 
they will pay for. Your study doctors or their clinical staff will obtain authorization from 
your insurance company prior to beginning your treatment. Taking part in this study may 
or may not cost you or your insurance company more than the cost of getting regular 
cancer treatment.
You will not be billed for any of the tests required specifically by the study. These are 
procedures noted above as “research procedures” in this consent form, such as DXA 
bone scans, blood drawn for research, and quality of life questionnaires. Other 
procedures, which are also done in this study but are part of your normal care, will be 
paid for by your or your insurance, such as hormone injections (these will be billed to 
you or your insurance as the Anddrogen deprivation therapy is standard of care for 
prostate cancer). This includes procedures that are considered part of the standard 
treatment for your cancer.
For more information on clinical trials and insurance coverage, you can visit the National 
Cancer Institute's Web site at http://cancer.gov/clinicaltrials/understanding/insurance-
coverage. You can print a copy of the "Clinical Trials and Insurance Coverage" 
information from this Web site.
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and 
ask them to send you a free copy.
WILL I BE PAID FOR TAKING PART IN THIS STUDY?
You will not be paid for taking part in this study.
WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THIS STUDY?
It is important that you tell your study doctors, Dr. Aggarwal, MD, and his associates, if 


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you feel that you have been injured because of taking part in this study. You can tell him 
in person or call him 
. 
Treatment and Compensation for Injury:  If you are injured as a result of being in this 
study, the University of California will provide necessary medical treatment. The costs of 
the treatment may be billed to you or your insurer just like any other medical costs, or 
covered by the University of California depending on a number of factors. The 
University does not normally provide any other form of compensation for injury. For 
further information about this, you may call the office of the Committee on Human 
Research at 415- 476-1814. 
WHAT ARE MY RIGHTS IF I TAKE PART IN THIS STUDY?
Taking part in this study is your choice. You may choose either to take part or not to 
take part in the study. If you decide to take part in this study, you may leave the study at 
any time. No matter what decision you make, there will be no penalty to you and you will 
not lose any of your regular benefits. Leaving the study will not affect your medical care. 
You can still get your medical care from our institution. 
We will tell you about new information or changes in the study that may affect your 
health or your willingness to continue in the study.
In the case of injury resulting from this study, you do not lose any of your legal rights to 
seek payment by signing this form.
WHO CAN ANSWER MY QUESTIONS ABOUT THE STUDY?
You can talk to your study doctor about any questions, concerns, or complaints you 
have about this study. Contact your study doctor, Dr. Aggarwal, MD 
. 
If you wish to ask questions about the study or your rights as a research participant to 
someone other than the researchers or if you wish to voice any problems or concerns 
you may have about the study, please call the Office of the Committee on Human 
Research at 415-476-1814.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can search this Web site 
at any time.
************************************************************
Please note: This section of the informed consent form is about additional 
research studies that are being done with people who are taking part in the main 
study. You may take part in these additional studies if you want to. You can still 


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be a part of the main study even if you say "no" to taking part in any of these 
additional studies.
You can say "yes" or "no" to each of the following studies. Please mark your 
choice for each study.
Using Blood for Research:
If you allow it, during the main part of the study, the study doctor would like to collect 
blood (about 1 tablespoon) to look for genetic changes (genotyping). The doctors would 
like to analyze your blood so that they can determine if there are inherited differences in 
a subset of your genes involved in hormone biology, which may affect treatment side 
effects. This information may help doctors to better manage the treatment side effects of 
future cancer patients. 
The research is not designed specifically to help you. It might help people who have 
cancer and other diseases in the future.
Results from the analysis will be published but your data will not be reported 
individually. Reports about research done with your blood will not be given to you or 
your doctor. These reports will not be put in your health record. The research will not 
have an effect on your care.
Things to Think About
The choice to allow the additional blood collection is up to you. No matter what you 
decide to do, it will not affect your care.
If you decide now that your blood can be drawn for genotyping, you can change your 
mind at any time. Just contact the study doctor, Rahul Aggarwal, MD 
 
, and let us know that you do not want us to use your blood. Then any blood that 
remains will no longer be used for research.
 
In the future, people who do research may need to know more about your health. While 
UCSF may give them reports about your health, it will not give them your name, 
address, phone number, or any other information that will let the researchers know who 
you are.
Your blood will used for genetic research (about diseases that are passed on in 
families) during the study. Even when your blood is used for this kind of research, the 
results will not be put in your health records. 


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Your blood will be used only for research and will not be sold. The research done with 
your blood may help to develop new products in the future. You will not be paid for 
allowing your blood to be used in research even though the research done with your 
blood may help to develop new products in the future. You will not receive any payment 
or financial benefit from any products, tests, or discoveries derived from these samples.
Benefits
The benefits of research using blood include learning more about what causes cancer 
and other diseases, how to prevent them, and how to treat them.
Risks
The greatest risk to you is the release of information from your health records. We will 
do our best to make sure that your personal information will be kept private. The chance 
that this information will be given to someone else is very small.
Making Your Choice
Please read each sentence below and think about your choice. After reading each 
sentence, put your initials in the "Yes" or "No" box. If you have any questions, please 
talk to your doctor or nurse, or call our research review board at 415-476-1814.
No matter what you decide to do, it will not affect your care.
1. I allow my blood to be collected for genotyping.
YES 
NO
2. I agree to undergo the optional CT scans of the radius and tibia prior to start of the
study, and also after 12 months.
YES 
NO


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CONSENT
You have been given copies of this consent form and the Experimental Subject's Bill of 
Rights to keep.
You will be asked to sign a separate form authorizing access, use, creation, or 
disclosure of health information about you.
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to 
participate or to withdraw at any point in this study without penalty or loss of benefits to 
which you are otherwise entitled.
If you wish to participate in this study, you should sign below.
Participant
Date
Participant name (print)
Person obtaining consent
Date
Person obtaining consent 
(print)
Witness – Only required if the participant is a non-English 
speaker
Date