Clinical trial NCT03046836
Conditions: Alcohol Use
Keywords: Couples Oxytocin Aggression Alcohol
Sponsor: Medical University of South Carolina
Start date: 2017-07-01; Completion date: 2021-04-11
Enrollment: 200 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Alcohol use disorders (AUD) and intimate partner aggression (IPA) frequently co-occur. There are significant health and economic burdens associated with AUD and co-occurring IPA, and little empirical data to guide treatment efforts. The neuropeptide oxytocin may help mitigate both AUD and IPA. However, clinical data examining oxytocin's effects on human aggression is scant. The proposed study is designed to address these gaps in the literature by utilizing a human laboratory paradigm to test the effects of oxytocin on craving and aggression among couples with AUD and co-occurring IPA.

Detailed description:

Arms: arm 1: Each participant will self-administer 40 international units (IU) intranasal Oxytocin arm 2: Each participant will self-administer matching saline placebo
Interventions: intervention 1: Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: 40 IU oxytocin nasal spray intervention 2: Saline

Protocol documents:
ICF_001.pdf: 
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N C T 0 3 0 4 6 8 3 9  
Offici al Title: Effects of O x yt oci n o n Alc o h ol Cr a vi n g a n d I nti m ate P art ner 
Vi ole nce   
 


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Me dic al U ni versit y of S o ut h C ar oli n a  
C O N S E N T T O B E A R E S E A R C H S U B J E C T  
 
TI T L E O F R E S E A R C H:  Effects of O x yt oci n o n Alc o h ol Cra vi n g a n d I nti mate Part ner 
A g gressi o n  
 
A. P U R P O S E O F T H E R E S E A R C H  
Y o u are bei n g as ke d t o v ol u nteer f or a researc h st u d y. Researc h st u dies are v ol u ntar y a n d i ncl u de 
o nl y pe o ple w h o c h o os e t o ta ke part. Pleas e rea d t his c o nse nt f or m caref ull y a n d ta ke y o ur ti me 
ma ki n g y o ur decisi o n. As t he st u d y staff disc uss t his c o nse nt f or m wit h y o u, please as k hi m/ her t o 
e x plai n a n y w or ds or i nf or mati o n t hat y o u d o n ot clearl y u n dersta n d.  
T he p ur p ose of t his st u d y is  t o e xa mi ne t he effects of a me dicati o n calle d o x yt oci n o n c o u ples’ 
c o m m u nicati o n s kills a n d be ha vi ors , as well as alc o h ol cra vi n g. O x yt oci n is c urre ntl y a p pr o ve d 
b y t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) t o be gi ve n i ntra ve n o usl y t o i n d uce la b or i n pre g na nt 
w o me n. H o we v er, o x yt oci n is c o nsi dere d “i n vesti g ati o nal use” i n t his st u d y, mea ni n g t hat t he F D A 
has n ot a p pr o ve d it f or h el pi n g i m pr o ve c o m m u nicati o n s kills or cra vi n g . T his is a P hase II st u d y 
of o x yt oci n, mea ni n g t h at it has esta blis he d use f or ot her  p ur p oses a n d researc hers are n o w testi n g 
t his me dicati o n i n lar ger p o p ulati o ns. Y o u are bei n g as ke d t o partici pate beca use y o u are o ver 1 8 
years of a ge, y o u are i n a r o ma ntic r elati o ns hi p, a n d eit her y o u or y o ur part n er dri n ks alc o h ol. T he 
i n vesti gat or i n c har ge of t he st u d y is Dr. J ulia n ne Fla na g a n of t he Me dical U ni versit y of S o ut h 
Car oli na ( M U S C). A gra nt fr o m t he Nati o nal I nstit utes of Healt h ( NI H) will s p o ns or t his st u d y. 
P orti o ns of Dr. Fl a na ga n’s a n d her r esearc h tea m’s salaries will be pai d b y t his  gra nt. T his st u d y 
is bei n g c o n d ucte d i n C harlest o n, S C a n d will i n v ol ve a p pr o xi matel y 2 0 0 partici pa nts. 
B. P R O C E D U R E S  
If y o u deci de t o p artici p ate i n t he st u dy, t he f oll o wi n g will h a p pe n: 
1.  F irst y o u will be as ke d a fe w q u esti o ns i n or der t o scree n y o u f or st u d y eli gi bilit y, w hic h will 
ta ke  a p pr o xi matel y  1 5- 3 0  mi n utes.  D uri n g  t hat  ti me,  y o u  will  be  as ke d  t o  a ns wer  s o me  
q uesti o ns a b o ut y o urself s uc h as y o ur a ge, healt h, relati o ns hi p stat us a n d y o ur use of alc o h ol 
a n d dr u gs t o deter mi ne if y o u are eli gi ble t o partici pate.  
2.  If y o u ha ve rece ntl y start e d ta ki n g a prescri pti o n me dicati o n, y o u ma y be as ke d t o wait 4 wee ks 
u ntil y o u partici pate i n t he st u d y s o t hat t he effects of t he me dicati o n will be sta ble a n d w o n’t 
affect t he st u d y res ults. 
3.  If y o u meet i nitial eli gi bilit y criteria a n d y o u c h o ose t o partici pate, y o u a n d y o ur part ner will 
be i n vite d t o  a n assess m e nt sessi o n  eit her i n p ers o n or via h o me base d tel e healt h . Tele healt h 
is a pr ocess i n w hic h y o u will be c o n necte d t o st u d y staff fr o m t he c o mf ort of y o ur h o me b y usi n g 
V A  a p pr o ve d  vi de o  tec h n ol o g y.  Bef ore  we  be gi n,  y o u  a n d  y o ur  part ner  will  c o m plete  a  
breat hal yzer or s ali va alc o h ol test. If y o u are a w o ma n, y o u will be as ke d t o c o m plete a uri ne 
pre g na nc y test. T he uri ne pre g n a nc y test m ust b e ne gati ve i n or der t o p artici pate. If y o ur 


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pre g na nc y test is ne gati v e, or if y o u are male, y o u will be as ke d t o pr o vi de a uri n e sa m ple t o 
test for dr u g use  if t he a p p oi nt me nt is bei n g c o n d ucte d i n office. Y o u will als o be as ke d t o 
pr o vi de a  bl o o d sa m ple, if p ossi ble,  t o meas ure le vels of o x yt oci n nat urall y occ urri n g i n y o ur 
b o d y. O nl y o ne bl o o d sa m ple ma y  be ta k e n d uri n g t he st u d y (a b o ut a s p o o nf ul a m o u nt).  All 
re q uire d testi n g materi als will be s hi p pe d t o y o u if y o u c o m plete t he assess me nt a p p oi nt me nt 
via tele healt h.  
4.  T he assess me nt a p p oi nt me nt will last a p pr o xi matel y 2- 3 h o urs. After t he breat hal yzer , bl o o d, 
a n d  uri ne  tests  are  c o m plete d,  y o u  a n d  y o ur  part ner  will  be  as ke d  t o  fill  o ut  s o me  
q uesti o n naires. T hese q uesti o n naires will as k y o u a b o ut y o ur me ntal a n d p h ysical healt h, 
e x p os ure t o tra u ma, us e of alc o h ol a n d dr u gs, a n d y o ur rel ati o ns hi p wit h y o ur part n er. Y o u d o 
n ot ha ve t o a ns wer a n y q uesti o ns t hat y o u d o n ot wa nt t o a ns wer.  
5.  After t he ass ess me nt a p p oi nt me nt a n d if b ot h part ners meet eli gi bilit y criteria , we will eit her 
sc he d ule  or  be gi n  t he  la b orat or y  sessi o n,  w hic h  will  last  a p pr o xi matel y  3-4  h o urs.  T he  
assess me nt a n d la b orat or y sessi o ns ma y ta ke u p t o   2  a p p oi nt me nts. D uri n g t he la b orat or y 
sessi o n w e will ta ke se veral meas ure me nts  i ncl u di n g y o ur heart rate a n d bl o o d press ure. Yo u 
ma y als o be as ke d t o pr o vi de  sali va sa m ples t o meas ure t he le vels of stress-relate d h or m o n es. 
N ote t hat y o u ma y n ot pr o vi de a n y sali va sa m ples if t he st u d y tea m deter mi nes s o met hi n g 
a b o ut y o ur healt h t hat mi g ht affect st u d y res ults (i ncl u di n g rece nt c o ns u m pti o n of caffei ne or 
f o o d, me dicati o ns t hat affect o x yt oci n (e. g., a n dr o d gel, le v ot h yr o xi ne, etc.) or ot her fact ors). 
6.  Ne xt, y o u will be ra n d o ml y assi g ne d (li ke fli p pi n g a c oi n) t o recei v e eit h er a 4 0 i nter n ati o nal 
u nit (I U) d ose of o x yt oci n or a place b o (i.e., a n i nacti ve s u bsta nce). T h e o x yt oci n or place b o 
will be gi ve n t o y o u i n t he f or m of a n asal s pra y c o ntai ni n g eit her 4 0 I U o x yt oci n or s ali ne 
s pra y.  
7.  After a rest p eri o d, y o u will c o m plete a 1 0- mi n ute alc o h ol c ue t as k d uri n g w hic h y o u h ol d a n d 
s mell glasses of water a n d alc o h ol.  
8.  T he n, y o u a n d y o ur p art n er will c o m plete a 1 0- mi n ute reacti o n ti me tas k o n t he c o m p uter.  
9.  If y o u i n dicate d uri n g t he assess me nt i nter vie ws or o n t he q uesti o n naires t hat y o u mi g ht har m 
y o urself or s o me o ne else, we will as k y o u t o si g n a “safet y pla n ”. T his safet y pla n is a pr o mise 
y o u ma ke t o us t hat y o u will call a n e mer ge nc y n u m ber we gi v e y o u or 9 1 1, a n d t hat y o u a gree 
t o refrai n fr o m h urti n g y o urself or s o me o ne else. T he n u m bers t o call will be o n t he safet y pla n 
c o ntract. We will als o gi ve y o u a list of l ocal treat me nt referrals.  If yo u d o n ot a gree t o t he 
safet y pla n, w e will esc ort y o u t o t he E mer ge nc y De part me nt t o hel p e ns ure y o ur safet y.  
1 0.  Y o u will be c o m pe nsate d f or y o ur ti me a n d gi v e n referrals f or l ocal treat me nt ce nters  as 
nee de d . 
1 1.  T he i n vesti gat ors reser ve t he ri g ht t o disc o nti n ue st u d y partici pati o n f or a n y i n di vi d ual w h o is 
deter mi ne d t o be a t hreat t o self, staff, ot her st u d y partici pa nts, or w h o is u na ble t o c o m plete 
t he st u d y assess me nts or pr o vi de i nf or me d c o ns e nt. 
 
T E L E H E A L T H  
 
If t h er e i s a n yt hi n g t h at m a k e s it diffi c ult f or y o u t o c o m e t o t h e M U S C, h o m e -b a s e d 
t el e h e alt h ( H B T) i s a v ail a bl e f or t h e a s s e s s m e nt a p p oi nt m e nt p orti o n of t h e st u d y. I n or d er 
t o c o m pl et e t h e s e s si o n vi a H B T, y o u will n e e d t o h a v e i nt er n et or c ell ul ar a c c e s s i n y o ur 


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h o m e a n d a c o m p ut er, t a bl et, or s m art p h o n e c a p a bl e of a c c e s si n g t h e i nt er n et. If y o u 
c o m pl et e  t h e  a s s e s s m e nt  a p p oi nt m e nt  vi a  t el e h e alt h,  bi ol o gi c al  m e a s ur e s  a n d  
s p e ci m e n s will n ot b e c oll e ct e d. Pr e g n a n c y t e st s  a n d  al c o h ol s ali v a t e st s will b e s hi p p e d 
t o y o u vi a tr a c k a bl e o v er ni g ht U P S s hi p m e nt. F e m al e s will b e r e q uir e d t o pr o vi d e v er b al 
a n d p h ot o ( of di p sti c k) c o nfir m ati o n of a n e g ati v e pr e g n a n c y t e st.  
Y o u will b e a s k e d t o fi n d a pri v at e r o o m, a w a y fr o m  y o ur p art n er f or p orti o n s of t h e 
a s s e s s m e nt a p p oi nt m e nt. T h e st u d y t e a m c a n al s o w or k wit h y o u a n d y o ur p art n er t o 
s c h e d ul e t h e s e p orti o n s i n di vi d u all y a n d s e p ar at el y i n or d er t o m ai nt ai n pr ot e cti o n of y o u r 
pri v a c y. 
If y o u a n d y o ur p art n er d o n ot li v e t o g et h er, st u d y s u p pli e s will b e s hi p p e d t o o n e ( a gr e e d 
u p o n) r e si d e n c e.  
I n t h e e v e nt y o u ar e u n a bl e t o m a k e it t o t h e offi c e f or y o ur a s s e s s m e nt a p p oi nt m e nt , t h e 
st u d y t e a m m a y s e n d y o u st u d y s u p pli e s  vi a U P S.  W e w o ul d li k e y o ur c o n s e nt t o s hi p 
st u d y s u p pli e s  t o t h e a d dr e s s pr o vi d e d o n y o ur c o nt a ct i nf or m ati o n f or m.  
Pl e a s e i n di c at e y o ur c h oi c e b el o w , or s cr oll d o w n t o t h e b ott o m of t h e s cr e e n a n d s el e ct y o ur 
c h oi c e el e ctr o ni c all y: : 
 
_ _ _ _ Y e s, I w o ul d li k e st u d y s u p pli e s  s hi p p e d t o m y r e si d e n c e if I a m u n a bl e t o m a k e m y 
a p p oi nt m e nt, or i n t h e e v e nt M U S C i s cl o s e d.  
_ _ _ _ N o, I w o ul d n ot li k e st u d y s u p pli e s  s hi p p e d t o m y r e si d e n c e if I a m u n a bl e t o m a k e 
m y a p p oi nt m e nt, or i n t h e e v e nt M U S C i s cl o s e d.      
 
C. D U R A TI O N  
 
Partici pati o n i n t he st u d y will ta ke a b o ut 6 h o urs, w hic h ca n b e di vi de d i nt o t w o visits.  
 
D.  RI S K S A N D DI S C O M F O R T S  
O x yt oci n: T he F D A has a p pr o ve d o x yt oci n f or use a m o n g w o me n d uri n g la b or. W he n us e d 
i ntra ve n o usl y t o i n d uce l a b or, a d vers e effects ass ociate d wit h o x yt oci n ha ve i ncl u de d seiz ures, 
me ntal dist ur ba nces, n a usea, v o miti n g, irre g ular heart beat, hi g h bl o o d press ure, a n d u ne x p ecte d 
blee di n g or c o ntracti o n of t he uter us i n a s mall n u m ber of w o me n.  W h e n use d as a n asal s pra y, 
ot her si de effects ma y i ncl u de nasal irritati o n, r u n n y n ose, a n d teari n g of t he e y es.  H o w e ver, 
se veral st u dies ha v e bee n c o n d ucte d i n h u ma ns wit h i ntra nasal d oses si milar t o w hat will be use d 
i n t his st u d y, a n d n o a d verse si de effects h a ve bee n re p orte d. 
I nter vie ws a n d S ur v e ys: Beca use t his st u d y i n v ol ves a ns w eri n g q u esti o ns a b o ut a n d disc ussi n g 
t o pics  of a pers o nal  a n d s o meti mes  se nsiti ve nat ure, y o u ma y bec o me  u pset. Y o u ma y als o 
e x perie n ce s o me p h ysical or e m oti o nal distress d uri n g t he i nter vie ws, t he la b orat or y tests, or t he 
reacti o n ti me tas k o n t he c o m p uter. If y o u feel si g nifica nt distress at a n y ti me, y o u ma y st o p filli n g 


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o ut t he q uesti o n naires or deci de t o st o p t he reacti o n ti me tas k o n t he c o m p uter. Y o u d o n ot ha ve 
t o a ns wer a n y q uesti o ns t hat y o u d o n ot wa nt t o a ns wer. Y o u ma y als o bec o me tire d or b ore d w hile 
c o m pleti n g s o me of t he assess me nts. 
Ris ks t o pre g na nt w o me n:  If y o u ar e a w o ma n  of c hil d beari n g p ote ntial, y o u will recei ve a 
pre g na nc y t est, a n d if pre g na nt, y o u will n ot be all o we d t o partici pate i n t he st u d y as o x yt oci n ca n 
i n d uce la b or. If y o u are ca pa ble of b ec o mi n g pre g na nt, y o u m ust be usi n g a me dicall y a p pr o v e d 
met h o d of birt h c o ntr ol (s uc h as a bsti ne nce, s ur gical sterilizati o n, c o ntrace pti ve pills, dia p hra g ms, 
or ot her f or ms of barrier c o ntrace pti ves) a n d y o u m ust c o nti n ue t o d o s o d uri n g t he c o urse of t he 
st u d y. F or tele healt h partici pa nts, st u d y staff will re q uire a ver b al c o nfir mati o n of t he ne gati ve 
pre g na nc y t est pri or t o c o nti n ui n g wit h t he assess me nts. 
C o nfi de ntialit y:  All st u d y rec or ds will be place d i n a l oc ke d, sec ure, li mite d access l ocati o n. Y o ur 
partici pati o n i n t he st u d y a n d t he i nf or mati o n y o u pr o vi de will be treat e d as c o nfi de ntial. T he 
i nf or mati o n we c ollect will c o ntai n y o ur i nitials a n d/ or c o de n u m ber a n d n ot y o ur na me t o pr ot ect 
y o ur c o nfi de ntialit y. C o des li n ki n g n u m bers a n d na mes will be ke pt i n a l oc ke d sec ure l ocati o n 
a n d will n ot be accessi ble t o a n y o ne o utsi de t he researc h tea m. Y o u s h o ul d als o k n o w t hat if y o u 
t hreate n t o har m y o urself or ot hers or gi v e i nf or mati o n a b o ut c hil d or el der a b use, t his i nf or mati o n 
will be re p orte d t o a p pr o priate cli nical staff a n d ot her pers o ns o utsi de t h e researc h pr o gra m as 
necessar y t o pr otect y o urself a n d ot hers as ma n dat e d b y la w.  
T he e x peri me ntal treat me nt ma y ha ve u n k n o w n si de effects. T he researc h ers will let y o u k n o w if 
t he y lear n a n yt hi n g t hat mi g ht ma ke y o u c ha n ge y o ur mi n d a b o ut partici p ati n g i n t he st u d y. 
E. B E N E FI T S  
Si nce t his is a r esearc h st u d y a n d n ot a treat me nt st u d y, t here ma y be n o direct be n efit t o y o u  fr o m 
partici pati n g i n t his st u d y. H o we ver, it is h o pe d t hat t he i nf or mati o n gai ne d fr o m t his st u d y will 
hel p us de vel o p better tr eat me nts f or c o u ples. 
F. C O S T S  
 
T here will be  n o c ost t o y o u as a res ult of p artici pati o n i n t his st u d y.  
G. P A Y M E N T T O P A R TI CI P A N T S  
 
I n r et ur n f or y o ur ti me a n d eff ort, y o u will be c o m pe nsate d i n t he f or m of cas h, c hec k, or gift car ds. 
If c o m pleti n g t he assess me nt p orti o n via tele healt h, y o u ma y wait t o be rei m b urse d d uri n g y o ur i n-
pers o n la b visit or y o u ma y be maile d a c hec k or gift car d via U S P S . Y o u a n d y o ur part ner will eac h 
recei v e $ 15 0 f or c o m pleti n g all st u d y re q uire me nts. If y o u c h o ose n ot t o c o m plete t he st u d y, y o u 
will  be  c o m pe nsate d  f or  t he  part(s)  y o u  ha ve  c o m plete d.  Eac h  part ner  will  recei ve  $ 2 5  f or  
c o m pleti n g  t he bas eli ne q uesti o n naires a n d i nter vi e ws a n d $1 2 5 f or c o m pleti n g t he e ntiret y of t he 
la b orat or y  assess me nt  pr oce d ur es.    If y o u arri v e d wit hi n 3 0 mi n utes of y o ur first sc he d ule d 




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J.  SI G NI FI C A N T N E W FI N DI N G S  
 
If t here ar e si g nifica nt ne w fi n di n gs d uri n g t he c o urse of t he st u d y, y o u will be n otifie d.  
 
K. S T U D E N T P A R TI CI P A TI O N  
 
Y o ur  partici pati o n  or  disc o nti n ua nce  will  n ot  c o nstit ute  a n  ele me nt  of  y o ur  aca de mic  
perf or ma n ce , n or  will  it  be  a  part  of  y o ur  aca d e mic  rec or d  at  t his  I nstit uti o n.  
 
L. E M P L O Y E E P A R TI CI P A TI O N  
 
Y o ur partici p ati o n or disc o nti n ua nce will n ot c o nstit ute a n ele me nt of y o ur j o b perf or ma nce or 
e val uati o n , n or  will  it  be  a  part  of  y o ur  pers o n nel  rec or d  at  t hi s  I nstit uti o n. 
 
M.  C LI NI C A L T RI A L S. G O V   
 
A descri pti o n of t his cli nical trial will be a vaila bl e o n htt p:// w w w. Cli nical Trials. g o v , as re q uire d 
b y U. S. La w. T his We b site will n ot i ncl u de i nf or mati o n t hat ca n i de ntif y y o u. At m ost, t he We b 
site will i ncl u de a s u m mar y of t he res ults. Y o u ca n searc h t his We b site at a n y ti me. 
N . F D A R E G U L A T E D 
Res ults of t his researc h will be use d f or t he p ur p oses descri be d i n t his st u d y. T his i nf or mati o n ma y 
be p u blis he d, b ut y o u  will n ot be i de ntifie d. I nf or mati o n t hat is o btai ne d c o ncer ni n g t his researc h 
t hat ca n be i de ntifie d wit h y o u will re mai n c o nfi de ntial t o t he e xte nt p ossi ble wit hi n State a n d 
Fe deral la w. T he s p o ns or a n d t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) will recei v e  c o pies of t he 
researc h rec or ds. T h e i n v esti gat ors ass oci ate d wit h t his st u d y, e m pl o yees of t he s p o ns or, a n d t he 
M U S C  I nstit uti o nal  Re vie w  B oar d  f or  H u ma n  Researc h  will  ha ve  access  t o  i de ntif yi n g  
i nf or mati o n. All rec or ds i n S o ut h Car oli na are s u bj ect t o s u b p oe na b y a c o urt of la w.  
 
I n t he e v e nt t hat y o u are i nj ure d as a res ult of partici pati o n i n t his st u d y, y o u s h o ul d i m me diatel y 
g o t o t he e mer ge nc y r o o m of t he Me dical U ni versit y H os pital, or i n case of a n e mer ge n c y g o t o 
t he near est h os pital, a n d tell t he p h ysicia n o n call t hat y o u are i n a researc h st u d y. T he y will call 
y o ur st u d y d oct or w h o will ma ke arra n ge me nts f or y o ur treat me nt. If t he st u d y s p o ns or d oes n ot 
pa y f or y o ur treat me nt, t he Me dical U ni versit y H os pital a n d t he p h ysicia ns w h o re n der treat m e nt 
t o y o u will bill y o ur i ns ur a nce c o m pa n y. If y o ur i ns ura nce c o m pa n y de ni es c o vera g e or i ns ura nce 
is n ot a vaila ble, y o u will be res p o nsi ble f or pa y me nt f or all ser vices re n d ere d t o y o u.  
Y o ur partici pati o n i n t his st u d y is v ol u ntar y. Y o u ma y ref use t o ta ke part i n or st o p ta ki n g part i n 
t his st u d y at a n y ti me. Y o u s h o ul d call t he i n vesti gat or i n c har g e of t his st u d y if y o u deci d e t o d o 
t his. Y o ur decisi o n n ot t o ta ke part i n t he st u d y will n ot affect y o ur c urre nt or f ut ure me dical care 
or a n y b e nefits t o w hi c h y o u ar e e ntitle d. T h e i n vesti gat ors a n d/ or t h e s p o ns or ma y st o p y o ur 
partici pati o n i n t his st u d y at a n y ti me if t he y deci de it is i n y o ur best i nterest. T he y ma y als o d o 
t his if y o u d o n ot f oll o w t he i n vesti gat or’s i nstr ucti o ns. 


Pa ge 8  of 1 0  
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O.  C O N S E N T F O R O P TI O N A L G E N O MI C R E S E A R C H  
 
Ge n o mic res ear c h is t he st u d y of h o w y o ur g e n es w or k.  G e n o mic researc h is a n i ncreasi n gl y 
i m p orta nt wa y t o tr y t o u n dersta n d t he r ole of g e nes i n h u m a n h ealt h . We are c o n d u cti n g a n 
o pti o nal s u b -st u d y t o e xa mi ne ge n o mic ass ociati o ns wit h healt h o utc o mes s uc h as s u bsta nce use . 
As part of t his o pti o nal s u b -st u d y, we w o ul d li k e t o c ollect a n d st ore a n a d diti o nal 7 milliliters 
(a b o ut 2 teas p o o ns ) of bl o o d . Y o u  will ha v e y o ur bl o o d dra w n, if p ossi ble,  f or t he mai n st u d y a n d 
partici pati n g i n t he o pti o nal ge netic s u b-st u d y will n ot re q uire a n e xtra nee dle stic k.  
 
T here are se veral t hi n gs y o u s h o ul d k n o w bef ore y o u deci de w het her t o partici pate i n t his o pti o n al 
s u b-st u d y: 
 
1)  Y o ur bl o o d sa m ple will be st ore d at t he M U S C Researc h Ne x us. We will ma ke e v er y eff ort t o 
pr otect y o ur i de ntit y b y gi vi n g y o ur bl o o d sa m ple a n u meric c o d e. O nl y st u d y pers o n nel ca n 
li n k t he c o de bac k t o y o u. W hile we h o pe t his will pre ve nt a n y p ote ntial l oss of pri vac y or 
c o nfi de ntialit y, we ca n n ot ma ke a n y g uara ntees. 
 
2)  S o meti mes t hese sa m ples are s hare d f or res earc h p ur p oses wit h ot her i n vesti gat ors at ot her 
researc h sites. Y o ur s a m ple ma y als o be se nt off site f or testi n g. If t his is d o ne, t he ot her 
i n vesti gat ors w o ul d n ot k n o w y o ur na me. Y o ur sa m ple will be destr o ye d wit hi n 6 years of 
st u d y c o m pleti o n. 
 
3)  All ge n o mic researc h will be d o ne at a n a g gre gate ( gr o u p) le v el. I n di vi d ual le vel D N A will be 
ge n ot y pe d b ut it will n ot be i nter pret e d or s hare d.  
 
4)  I n a d diti o n t o y o ur na me, ot her i nf or mati o n a b o ut y o u mi g ht be c o n necte d t o y o ur sa m ple. F or 
i nsta nce, i nf or mati o n a b o ut race, et h nicit y, or se x mi g ht be a vaila ble t o i n vesti gat ors st u d yi n g 
y o ur s peci me n. S uc h i nf or mati o n mi g ht be i m p orta nt f or researc h or p u blic h ealt h. It is p ossi ble 
t hat t his i nf or mati o n (i ncl u di n g ge netic i nf or m ati o n) mi g ht c o me t o be ass ociate d wit h y o ur 
racial or et h nic gr o u p. 
 
5)  Y o u ha ve t he ri g ht t o ref use t o all o w y o ur bl o o d t o be st u die d or sa ve d f or f ut ure researc h 
st u dies. Y o u ma y wit h dra w fr o m t his st u d y at a n y ti me a n d re m o ve a n y sa m ples t hat c o ntai n 
i de ntifiers fr o m res ear c h use after t he date of y o ur wit h dra w al. T his m ea ns t hat w hile t he 
U ni versit y mi g ht retai n t he i de ntifie d sa m ples (t he la w ofte n re q uires t his) t he y w o ul d n ot be 
use d f or r esearc h.  
 
6)  S o ut h Car oli na la w ma n d ates t hat y o ur g e netic i nf or mati o n o btai ne d fr o m a n y tests or fr o m t his 
researc h be ke pt c o nfi de ntial. O ur state la w pr o hi bits a n y i ns urer usi n g t his i nf or mati o n i n a 
discri mi nat or y ma n ner a gai nst y o u or a n y of y o ur fa mil y i n iss ui n g or re ne wi n g i ns ura nce 
c o vera g e f or y o u or y o ur fa mil y. O ur state la w f urt her pr o hi bits o ur s hari n g y o ur ge netic 
i nf or mati o n wit h a n y o ne e xce pt i n a fe w narr o w circ u msta nces, o ne of t h ose bei n g a researc h 
pr oject of t his t y pe, a p pr o ve d b y t he I nstit uti o n al Re vie w B oar d a n d t he n we m ust ta ke all ste ps 


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t o pr otect y o ur i de ntit y. Y o u will still be res p o nsi ble f or p a yi n g f or healt h care, h o we v er. T he 
Me dical U ni versit y of S o ut h Car oli na will n ot be res p o nsi ble f or s uc h c osts, e ve n if care is 
nee de d f or a c o n diti o n re veale d d uri n g researc h or cli nical testi n g.  
 
7)  Ge netic r esearc h rais es diffic ult q uesti o ns a b o ut i nf or mi n g y o u a n d ot her s u bjects of a n y res ults, 
or of f ut ure res ults. S o me pe o ple feel a n xi o us a b o ut t he p ossi bilit y of ha vi n g a defecti ve ge ne 
t hat w o ul d place t he m or t heir c hil dre n at ris k. S o me pe o ple wa nt t o k n o w w hat is f o u n d o ut 
a b o ut t he m; ot hers d o n ot. T he ris ks of k n o wi n g i ncl u de a n xiet y a n d ot her ps yc h ol o gical 
distress. T he ris ks of n ot k n o wi n g w hat is f o u n d i ncl u de n ot bei n g a ware if t here is treat me nt 
f or t he pr o ble m bei n g st u die d. B ut t hese ris ks ca n c ha n g e de pe n di n g o n w het her t her e is a 
treat me nt or c ure f or a partic ular disease, a n d o n h o w clear t he res ults are. If t here is a me dical 
reas o n t o see k s pecific i nf or mati o n fr o m y o u, y o ur d oct or will tell y o u t his. A pr ocess calle d 
“ ge netic c o u n seli n g” is ofte n a p pr o priate i n s uc h cases; y o u s h o ul d as k y o ur d oct or a b o ut t his 
if y o u ha ve a n y q uesti o ns. I n t his st u d y, i n vesti gat ors will n ot tell y o u w hat t he y fi n d o ut a b o ut 
y o u, n or will t he y c o ntact y o u if a t est bec o mes a vaila ble t o dia g n ose a c o n diti o n y o u mi g ht 
ha ve or mi g ht later d e vel o p.  
 
8)  If y o u are c o ncer ne d a b o ut a p ote ntial ge netic dis or der, y o u a n d y o ur d oct or mi g ht c h o ose t o 
test s pecificall y f or it. T his w o ul d re q uire a d diti o nal bl o o d or tiss ue sa m ples t hat w o ul d n ot b e 
part  of  t his  res earc h  pr oject.  Y o u  s h o ul d  disc uss  t his  o pti o n  wit h  y o ur  d oct or  or  ge netic  
c o u nsel or. 
 
9)  T he prese n ce of a ge neti c mar ker d oes n ot necess aril y mea n t hat a n i n di vi d ual will de vel o p a 
disease.  I nf or mi n g  pe o ple  of  all  s uc h  mar kers  i n de pe n de ntl y  of  me dical  nee d  c a n  ca use  
u n necessar y a n xiet y. O n t he ot her ha n d, t he a bse nce of a mar ker d oes n ot mea n t hat s o me o ne 
will n ot get t he disease. Ge netic diseases a p p ear as a res ult of a c o m ple x mi xt ure of here ditar y, 
e n vir o n me ntal, be ha vi oral a n d ot her fact ors. 
 
T hese ar e t h e best k n o w n ris ks a n d c halle n ges of ge netic researc h. T here mi g ht be ot her ris ks 
we d o n ot k n o w a b o ut yet. It is i m p orta nt t hat y o u tal k t o y o ur d oct or if y o u ha ve q uesti o ns or 
c o ncer ns a b o ut t he res ear c h st u d y. 
 
Y o u ha ve t he o pti o n of ref usi n g t o s u b mit y o ur sa m ple f or ge netic res earc h, a n d still partici pate 
i n t he rest of t he st u d y. Please i n dicate y o ur prefere nce bel o w , or s cr oll d o w n t o t he b ott o m of 
t he scree n a n d select y o ur c h oice electr o nicall y: 
 
 Yes, I a gr ee t o ha ve m y bl o o d sa ve d f or t he d urati o n of t he st u d y a n d use d f or ge netic testi n g 
i n t he f ut ure.    
 N o, I d o n ot a gree t o ha ve m y bl o o d sa ve d f or t he d urati o n of t he st u d y a n d t o be use d f or 
ge netic testi n g i n t he f ut ure.   
 
 
 
 



Prot_SAP_002.pdf: 
Page 1 of 27
Version 23; 11.13.2020 
NCT03046836 
PROTOCOL TITLE: Effects of Oxytocin on Alcohol Craving and Intimate Partner 
Aggression 
PRINCIPAL INVESTIGATOR: Julianne C. Flanagan, Ph.D. 


Version 23; 11.13.2020 
 
Page 2 of 27 
 
1.0 
Objectives / Specific Aims 
 
Alcohol use disorders (AUD) and intimate partner aggression (IPA) frequently co-occur. 
AUD is commonly associated with IPA perpetration14-16 as well as victimization14,17-19. Indeed, 
AUD is responsible for a substantial portion of the $4 billion in health care costs that U.S. 
taxpayers sustain annually as a result of IPA20-24.  Behavioral interventions to reduce AUD and 
co-occurring IPA have received moderate, but inconsistent support 25-28. Thus, there is a critical 
need to develop more effective interventions to reduce AUD and co-occurring IPA. 
The neuropeptide oxytocin has been shown to significantly attenuate hypothalamic–pituitary–
adrenal (HPA) axis dysregulation, which is a well-established correlate of both AUD and 
aggression29-32. Oxytocin has demonstrated the ability to reduce stress-induced craving, drug-
seeking behaviors, and relapse among individuals with alcohol, marijuana, cocaine, or stimulant 
use disorders32-36. Notably, these are the substances most strongly and consistently linked with 
IPA37,38. Clinical and preclinical research also indicate that oxytocin promotes prosocial behavior 
and reduces negative affect and aggression39-41. Preliminary findings among normative human 
couples suggest that oxytocin may also reduce dyadic conflict42.  Thus, oxytocin may effectively 
reduce alcohol craving and IPA.  However, this topic has not yet been investigated. 
 
A significant barrier to the investigation of AUD and co-occurring IPA is the scarcity of 
studies employing laboratory paradigms to measure IPA.  Human laboratory paradigms have 
been used extensively to advance the study of craving and AUD29,43,44. This methodology is 
essential to develop interventions to reduce AUD and co-occurring IPA. The current study will 
address this gap in the literature by utilizing the well-validated Taylor Aggression Paradigm 
(TAP)2  to examine the effects of oxytocin (40 IU) or placebo on (1) alcohol craving, (2) laboratory-
induced IPA, and (3) subjective, physiological, and neuroendocrine reactivity in couples with AUD 
and IPA. To accomplish this, we will employ a double-blind, placebo-controlled design.  The 
sample will include 100 couples in which one or both partners meet diagnostic criteria for current 
AUD and report IPA within the current relationship. The following Specific Aims are proposed: 
 
Specific Aim 1: Examine the effects of intranasal oxytocin (40 IU) vs. placebo on subjective 
alcohol craving and aggression in response to the Taylor Aggression Paradigm (TAP) among 
couples with AUD and IPA. 
 
Specific Aim 2:  Examine the effects of intranasal oxytocin (40 IU) vs. placebo on physiological 
(i.e., heart rate, skin conductance) and neuroendocrine (i.e., cortisol,) response to the Taylor 
Aggression Paradigm (TAP) among couples with AUD and IPA. 
 
Specific Aim 3:  Identify predictors of oxytocin response (e.g., gender, endogenous oxytocin, IPA 
severity). 
 
We hypothesize that individuals who receive oxytocin, as compared to placebo, will 
demonstrate significantly lower alcohol craving and aggression, as well as lower physiological 
and neuroendocrine reactivity to the TAP.  Furthermore, we hypothesize that oxytocin response 
will be greater among women as compared to men.  While the existing literature examining the 
effects of endogenous oxytocin and potentially traumatic experiences, such as IPA, on oxytocin 
response is scant, we hypothesize that oxytocin response will be lower among individuals with 
higher endogenous oxytocin levels and greater IPA severity. 
 
 
 
 


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2.0 
Background 
 
AUD and IPA commonly co-occur. Alcohol use disorders (AUD) are consistently 
identified as both a precipitant and consequence of intimate partner aggression (IPA). In the 
general population, rates of IPA perpetration are 2 to 8 times higher among individuals with, as 
compared to without, AUD 1. Furthermore, rates of AUD are up to 6 times greater among 
individuals with, as compared to without, a history of IPA victimization2. Among treatment-seeking 
populations, high rates of co-occurring AUD and IPA have also been observed3. A strong temporal 
association has been established between alcohol use and IPA perpetration4-7 and between IPA 
victimization and AUD4,8, suggesting that AUD and IPA have a bi-directional nature. As the co-
occurrence of IPA in combination with AUD often reflects greater levels of aggression, severity 
and risk, being able to identify and treat co-occurring AUD and IPA is a significant health priority13-
15.  
The health burden associated with co-occurring AUD and IPA is extensive. The 
annual cost of AUD alone in the U.S. is over $600 billion9,10. More than one-third of Americans 
experience IPA during their lifetime11, costing taxpayers approximately $4 billion dollars annually 
in health care costs, lost time at work, and criminal justice expenses12,13. The high health care 
costs associated with IPA are known to persist even after IPA ends14. The health burden 
associated with co-occurring AUD and IPA is particularly malignant, resulting in increased risk of 
mortality from partner homicide and suicide, injury, physical health problems, psychiatric problems 
(e.g., PTSD, depression, anxiety, insomnia), HIV, and smoking13,15-22, and poor treatment 
outcomes23. Evidence that co-occurring AUD and IPA are transmitted across generations24 further 
highlights the significant and enduring societal health burden associated with this dual condition. 
There is a scarcity of effective treatments for co-occurring AUD and IPA. Several 
evidence-based psychosocial interventions for AUD have been developed25,26. However, relapse 
rates are high and there is significant room for improvement. Because AUD is a salient proximal 
and distal predictor of IPA27,28,  a strong theoretical rationale exists to use AUD treatments to help 
reduce AUD and IPA concurrently29,30. While recent research has found some promising 
reductions in IPA following AUD treatment31-33, findings are inconsistent and grow increasingly 
spurious following the end of treatment34-36. Thus, there remains a critical need to improve 
treatments for co-occurring AUD and IPA, including the exploration of pharmacological 
interventions.  
Inadequate measurement is a critical barrier to developing effective treatments for 
AUD and IPA 37,38. Researchers examining IPA rely primarily on self- or partner-report 
methodologies39 which are frequently influenced by factors such as recall bias, interdependency 
of partners’ behaviors, and non-agreement between partners’ reports which limit the reliability of 
IPA self-report data.  Whereas research integrating technological advances such as experience 
sampling methods, interactive voice response, and handheld devices to collect ecological 
momentary assessments have reduced this barrier, data indicate that these biases in the current 
state of data collection methodology remain39.  Thus, developing effective treatments for co-
occurring AUD and IPA remains difficult in the absence of more effective measurement strategies.  
Human laboratory paradigms have been useful in enhancing treatments for AUD40, 
but have not yet been applied to IPA. Laboratory paradigms utilized by Dr. Back (Primary 
Mentor) and others have successfully predicted craving41-45, relapse propensity46-48, and self-
initiated abstinence49. Laboratory paradigms such as those used by Dr. Becker (Co-Mentor)50-52 
have also facilitated the study of pharmacological interventions for AUD53. Human laboratory 
paradigms have been applied to the measurement of aggression54,55. However, IPA specifically 
has not yet been examined in the laboratory among AUD populations.  Applying well-controlled 
laboratory paradigms to the study of AUD and co-occurring IPA will: (a) allow for the identification 


Version 23; 11.13.2020 
 
Page 4 of 27 
 
of neurobiological risk and protective factors contributing to AUD and aggression,    (b) more 
precisely elucidate associations between risk factors and IPA compared to existing daily diary and 
experience sampling methods5,39, (c) examine aggression among both partners simultaneously, 
and (d) inform effective treatment development for AUD and IPA. 
Oxytocin may help reduce craving and aggression. Accumulating evidence suggests 
that oxytocin may help reduce the effects of social stress on alcohol use behaviors49,56. Few 
studies, however, have investigated the effects of oxytocin on human aggression. Oxytocin may 
help reduce IPA by reducing its known precipitating factors such as alcohol use, stress reactivity, 
and negative affect and by enhancing positive affect. No studies to date have examined the effects 
of oxytocin among individuals with AUD and co-occurring IPA. Further, accumulating evidence 
suggests that individual and contextual differences may influence concentrations of endogenous 
oxytocin and its effects on human behavior57.  The proposed study will address critical gaps in the 
literature by utilizing a well-controlled human laboratory paradigm (Taylor Aggression Paradigm) 
to examine the ability of oxytocin to reduce craving and aggression among couples with AUD and 
co-occurring IPA.  We will compare subjective, physiological and neuroendocrine responses to 
the laboratory test within-subjects before and after they receive oxytocin or placebo, and between-
subjects who receive either oxytocin or placebo. We will also examine individual, dyadic, and 
contextual factors that may influence oxytocin’s effects on craving and aggression, which will help 
inform future translational research focused on the use of oxytocin among AUD and IPA 
populations. 
 
3.0 
Intervention to be studied  
Oxytocin is a hypothalamic nonaneuropeptide that initiates physiologic events necessary 
for parturition and lactation58,59. Intravenous infusions of oxytocin are commonly administered 
among women during childbirth to facilitate labor and lactation and has FDA approval for this 
purpose. Scientific inquiry of intranasal oxytocin is growing at a rapid rate in the field of 
psychiatry. Current perspectives on the effects of oxytocin support its role in mitigating addictive 
behaviors49,60-64 and enhancing adaptive social behavior and cognition such as interpersonal 
trust65, recognition66, empathy67,68, generosity69. Preliminary findings indicate that oxytocin can 
enhance positive conflict resolution behaviors among couples70. Recent studies also suggest 
that individual and contextual factors such as gender and psychosocial history may inform the 
behavioral effects of oxytocin71-77.  
Oxytocin and placebo (saline) will be compounded by MUSC’s Investigational Drug 
Services (IDS) or Pitt Street Pharmacy in Mt. Pleasant. IDS will conduct randomization and keep 
a record of the blind. Once study fully transitions to use of Pitt Street Pharmacy, Anjinetta Johnson, 
the study Physician’s Assistant, will hold the blind. Participants will blow their nose, exhale through 
their nose, then spray into one nostril while inhaling, alternating nostrils until the 40 IU dose is 
achieved. A 40 IU dose has demonstrated extensive safety and efficacy, is within the normal 
dosing range, and one of the most common concentrations utilized in human research78-80. Dr. 
Moran-Santa Maria (Co-I) has an FDA IND to utilize oxytocin. 
 
4.0 
Study Endpoints  
Outcome measures include 1) alcohol craving, 2) aggression as measured by the Taylor 
Aggression Paradigm, 3) physiological (e.g. heart rate, skin conductance) and neuroendocrine 
reactivity(e.g., salivary cortisol) 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
 


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Page 5 of 27 
 
All participants will be at least 18 years of age or older. Women and members of minority groups 
will be eligible for participation.  
 
Inclusion criteria indicate that participants must (a) aged 18-75, (b) fluent in English, (c) endorse 
at least one instance of mild or moderate physical IPA with their partner as defined by the 
Revised Conflict Tactics Scale (CTS-2)97, (d) both partners must be willing to participate 
and (e) one or both partners must meet DSM-V diagnostic criteria for an alcohol use disorder 
(AUD). Concurrent substance use disorders (e.g., marijuana) is acceptable provided alcohol is 
the participant’s primary substance of choice.  
 
Exclusion criteria include (a) pregnancy or breastfeeding, (b) current or history of psychiatric 
or medical condition that could interfere with neuroendocrine function (e.g., hematological, 
endocrine, renal, or pulmonary disease; synthetic glucocorticoid or exogenous steroid therapy; 
psychotic, bipolar, eating disorders), (c) both partners with a BMI ≥ 39, (d) current suicidal 
ideation and intent, (e) severe physical or sexual IPA in the past as defined by the CTS-297, (f) 
initiation of psychotropic medication in the past 4 weeks, (g) acute alcohol withdrawal as indicated 
by a score of 8 or greater on the CIWA-Ar98, (h) a current or past diagnosis of epilepsy or history 
of seizures. 
 
6.0 
Number of Subjects 
 
A total of 200 participants comprised of 100 couples will participate in this study. 
 
7.0 
Setting 
 
All procedures will be conducted on the MUSC campus. Procedures can also be conducted via 
telehealth. 
 
8.0 
Recruitment Methods 
 
Recruitment will be conducted at the Center for Drug and Alcohol Problems (CDAP) at 
MUSC and in VA treatment clinics. There are approximately 436 inpatient and 822 outpatient 
annual admissions to CDAP. In 2014, there were 1,258 admissions to the program with the 
majority of patients seeking AUD treatment.  The Charleston VAMC Substance Abuse Treatment 
Center (SATC) received 1,253 new admissions in 2014.  Approximately 70-80% of weekly 
referrals meet criteria for AUD. The Charleston VAMC Couples and Family Clinic treats 
approximately 130 new unique couples each year. The study team will use a list provided by the 
VAMC to mail IRB approved recruitment letters. In addition, we will post IRB and R&D-approved 
recruitment flyers in other MUSC and VA treatment clinics and catchment areas. Advertisements 
will be placed on the internet (e.g., Craigslist and SCresearch.org). Participants who refer others 
to the study will be compensated $10 per randomized referral, allowing us to reach a wider pool 
of potential participating couples including couples from the community with IPV and AUD, in 
addition to treatment-seeking couples with IPV and AUD. Further, participants from past MUSC 
research studies who have consented to be contacted for future research studies will be recruited 
via telephone screening and/or e-mails. These individuals will be referred to us via other MUSC 
researchers, or they may have indicated consent to be contacted about future research studies 
within their MUSC medical records. The research team has used these methods successfully to 
recruit patients to clinical and laboratory studies. If recruitment is delayed during the first year, we 
will run advertisements in local newspapers and radio stations to ensure the target sample is 
achieved. 


Version 23; 11.13.2020 
 
Page 6 of 27 
 
 
EPIC will be used for recruitment. The study team will use an IRB approved letter and script to 
inform identified individuals about our study. 
 
College students ages 18-75 enrolled at area colleges and universities will be contacted from 
respective registrar lists (no participants will be recruited until an interinstitutional agreement is 
signed by the respective institution, submitted as an amendment to the MUSC IRB, and approved 
by the MUSC IRB). Potential participants will be sent a recruitment email that includes details 
about the study (e.g., time requirement, basic inclusion criteria, compensation), a link to the IRB 
approved screener, and contact information for the research team will be included in the email. 
Potential participants will also be contacted via phone.  
 
9.0 
Consent Process 
 
Potential participants will be given a full description of the study procedures and asked to 
read and sign an IRB-approved informed consent form before any study procedures or 
assessments are conducted. Individuals who were recruited from the VA will also be required to 
read and sign a VA R&D –approved consent. Informed consent will take place on the MUSC 
campus or via telehealth, using an IRB approved platform. Individuals who were recruited through 
the VA can be screened and assessed at the VA clinic site. Initial eligibility screening will be 
conducted by the PI or a trained research assistant by telephone or in person. If preliminary 
inclusion and exclusion criteria are met, staff will schedule an assessment appointment for the 
couple. In a private room apart from their partner, participants will be provided with a 
description of the nature and requirements of study participation, and asked to read and sign an 
IRB-approved consent form prior to beginning any study procedures. In the event of eConsent, 
the informed consent process will still take place privately. If couples do not have the ability to each 
have a private room for eConsent (within their residence(s), separate appointments may be 
arranged to maintain privacy and to meet with each individual partner separately. REDCap will be 
utilized for re-consents when coming to the office would place undue burden on the participant.  In 
the case of a VA consent, a VA consent document will either be mailed or emailed to the 
participant.  PI/study team will use government furnished equipment to video call with the 
participant and go over the document.  Once the document is signed, the participant will be asked 
to hold it up to the screen and a screenshot will be taken and saved for records 
 
10.0 Study Design / Methods 
 
Figure 1 below illustrates the study design.  
 
 
 
 
Telehealth: Participants in this research study may choose to complete the assessment 
appointment via home-based telehealth (HBT) care (i.e., service delivery to patients in their 
homes using consumer-friendly, video-conferencing technology) which may likely enhance 
retention by directly circumventing financial and transportation barriers associated with traveling 
to MUSC/VA for an in-person session. HBT sessions will be delivered via standard desk, laptop 


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computer, tablet, or smartphone running MUSC/VA approved applications. Participants who 
choose telehealth will be required to have their own computer, tablet, or smartphone; however, 
webcams will be provided to participants for these visits as needed. Participants will be mailed 
required materials such as alcohol saliva test strips and pregnancy tests. Separate appointments 
will be made with each partner for instances where study team needs to meet with each individual 
separately or privately.  
Biological samples will not be collected for individuals participating in HBT care, however prior to 
the assessment appointment the study team will mail pregnancy tests and alcohol saliva strips to 
test for pregnancy and recent alcohol use. The alcohol saliva strip must read white (indicative of 
0.00 BAC to validate the consent and prior to completing any study procedures. Further, prior to 
proceeding, females will be asked to take a pregnancy test and must provide verbal confirmation 
of a negative pregnancy test prior to proceeding with the assessment appointment.  
 
Female participants who complete the assessment appointment via telehealth will be required to 
take an at-home urine pregnancy test during that visit (provided by study team) and confirm a 
negative result (verbally and with photo of dipstick). The pregnancy tests used in this study are 
designed for at-home use, come with clear and simple instructions. In very rare and highly unlikely 
circumstances where the participant is unfamiliar with how to provide a urine sample or take an 
at-home pregnancy test, study staff can provide further instructions on how to provide a urine 
sample, how use the dipstick to test, and to differentiate between a positive and negative result. 
Ability and willingness to perform an at-home pregnancy test is required for telehealth female 
participants. 
 
Required study supplies for telehealth participants will be shipped overnight via trackable UPS.  
 
Assessment Procedures. Following informed consent, eligible participants will complete 
a breathalyzer or saliva alcohol test, urine drug screen, blood draw, and pregnancy test (for 
women). Participants will have the option to participate in genomic research by providing an 
extra 7 milliliters of blood during the study blood draw. Participants will complete a psychosocial 
and medical history assessment (see Table 2). Note that for telehealth participants, biological 
specimens will not be collected, however, female participants will be required to take a 
pregnancy test (provided by study staff) and will be required to verbally confirm a negative result 
prior to continuing with any procedures.  Provided that all inclusion and exclusion criteria are 
met, participants will be scheduled to complete the laboratory testing portion of the study. 
Participants will be instructed to abstain from caffeine, nicotine, alcohol or other substances of 
abuse prior to the laboratory testing procedure. Smokers will be asked to abstain from smoking 
during study procedures and offered a nicotine patch prior to participation.  Nicotine patch 
dosage will be determined by the number of cigarettes participants smoke daily (≥20 
cigarettes/day=21mg; 10–19 cigarettes/day = 14 mg patch; 5–9 cigarettes/day =7 mg patch).   
Human Laboratory Procedure. Participants will complete an alcohol cue reactivity task 
and the TAP procedure approximately 45 minutes after receiving a 40 IU intranasal dose of 
oxytocin or placebo (i.e., saline). In a recent review of oxytocin studies, 40 IU is within the normal 
dosing range for humans and is one of the most common single dose concentrations utilized in 
human research78. This literature indicates that a 40 IU dose is safe and effective in eliciting effects 
on HPA axis reactivity among participants with AUD78,79.  
Alcohol Cue Procedure. Consistent with the procedure developed by Monti and 
colleagues81, participants will spend 3 minutes holding and smelling a control beverage (water), 
and reactivity (e.g., craving, urge to use) will be assessed. Following a 3-minute rest period, 
participants’ preferred alcoholic beverage will be presented and poured into an appropriate glass 


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and they will spend 3 minutes holding and smelling the beverage. Subjective and physiological 
reactivity will be measured again.  
  
 
 
TAP Procedure. In the couple-specific TAP utilized in Dr. Parrott’s (Consultant) is his 
ongoing NIAAA-sponsored trial, participants engage in a fictitious reaction time competition with 
their partner. Participants are led to believe that their partner chooses whether or not they receive 
a shock and its intensity. Participants have the option to administer a shock to their partner and 
its intensity in response to a “winning” trial.  In reality, participants receive electric shocks in 
response to a “losing” trial at intervals randomly generated by the TAP software104.  IPA is 
operationalized as the number of shocks administered, intensity of the first “unprovoked” shock, 
proportion of maximum shocks selected, and average shock intensity. Each participant will 
receive the same number of shocks. Electric shocks are brief in duration (1 second), range in 
intensity from 25-250 mV, and are administered to two fingertips of the participant’s non-dominant 
hand. The TAP task entails 30 trials for a total duration of 12-14 minutes.  
At the outset of the TAP procedure, the words “Get Ready” appear on the computer screen 
in front of the participant. Then the words “Press the Spacebar” appear on the screen. Participants 
press and hold the space bar until the words “Release the Spacebar” appear on the screen, at 
which time the participant will release the spacebar as quickly as possible.  A “win” is indicated to 
the participant with the words “You Won. You May Give a Shock” appearing on the screen.  
TABLE 2.  ASSESSMENT MEASURES 
Construct 
Measure 
Eligibility 
•Phone Screen Questionnaire 
•Demographics 
•Health History Interview & Concomitant   
 Medications 
•Breathalyzer and Urine Drug Screen 
•Pregnancy (women only) 
•Mini International Neuropsychiatric Interview82 
•Revised Conflict Tactics Scale; CTS-283 
•Patient Health Questionnaire; PHQ-999 
Dyadic 
Functioning 
•Dyadic Adjustment Scale; DAS87 
• Emotional & Physical Infidelity88 
Substance Use 
•Revised Clinical Institute Withdrawal Assessment; CIWA-Ar89 
•Time Line Follow back; TLFB 90,91 
•Alcohol Use Disorders Test;AUDIT92 
•Drug Abuse Screening Test; DAST93 
•Fagerstrom Nicotine Dependence Test94 
·Marijuana Motives Questionnaire 
Mental Health 
•Traumatic Life Events Questionnaire; TLEQ96 
• PTSD Check List; PCL-597 
• Childhood Trauma Questionnaire; CTQ98 
•Patient Health Questionnaire; PHQ-999 
• Cognitive Emotion Regulation Questionnaire; CERQ-Short 101 
• Perceived Stress Scale -4; PSS-4 102 
• Interpersonal Sensitivity Measure;IPSM 103Impulsive Behavior Scale; UPPS 
Neuroendocrine 
•Endogenous Oxytocin (blood) Note: Collected unless staff learn of contraindications. 
•Cortisol (saliva) Note: Collected unless staff learn of contraindications. 
Physiological 
•Heart Rate (HR) 
•Blood Pressure (BP) 
Subjective 
•Visual Analogue Scale (VAS) 


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Following a winning trial, participants choose whether or not to shock their opponent and its 
intensity on a level ranging from 1 (very mild shock, definitely not painful) through 10 (intense 
shock, definitely painful).  A “loss” is indicated with the words “You Lost. You Will Get a Shock” 
appearing on the screen. The shock intensity received by the participant is randomly selected by 
the computer software within the calibrated range specified for each participant.   
Calibration: The finger stimulator apparatus (Colbourn Instruments, Whitehall, PA) is 
calibrated for each participant, controlling for individual differences in pain threshold that may 
influence shock selection. Two electrodes are attached to the participant’s middle and index finger 
on the non-dominant hand.  Each participant is administered 1-second shocks that increase 
stepwise beginning with the lowest possible intensity.  Participants are instructed to inform the 
researcher when the shocks are first detectable and then again when they experience a shock as 
painful.  During the actual TAP procedure, shock levels range from 1 to 10 and correspond to the 
participant’s 55% through 100% pain threshold.   
 
 
 
 
Manipulation Check: To maintain the 
façade of the experiment, participants are 
informed that the purpose of the study is to 
assess reaction time performance among 
intimate partners. Following the TAP, 
participants will be asked a series of 
questions to assess the experiment’s 
validity. 
 
Laboratory Testing. Table 3 includes the 
laboratory 
testing 
procedures. 
A 
modification of the Within Session Rating 
Scale105 will be used to assess subjective 
ratings including craving, stress, and 
anger. This 100 mm Visual Analogue Scale 
(VAS) is anchored from 0 (none) to 10 
(extreme). Heart rate and blood pressure 
will be collected with a BP Tru Heart Rate 
and Blood Pressure machine. Cortisol will 
be measured using Salimetrics Passive 
Drool enzyme immunoassay kit, which has 
a 0.91 correlation with serum samples and 
a sensitivity of <0.007 ug/dL. Saliva 
samples will be collected and immediately 
placed in storage at -20°C until assay. One 
blood draw will be completed to assess 
endogenous oxytocin. Blood will be centrifuged at 1500 rpm at 4˚C and stored at −70˚C. 
Commercial ELISA kits (Enzo Life Sciences) will determine oxytocin levels. Intra-assay 
coefficients of variation for oxytocin average 3-5% and inter-assay variation is <10%. 
 
Debriefing. 
Existing 
literature 
indicates 
that 
distress 
resulting 
from 
the 
TAP 
is 
manageable54,106,107. Debriefing will include full disclosure of the study’s purpose and the 
necessity of deception. Participants reporting >5 on any VAS subscale will be asked to remain in 
TABLE 3.  LABORATORY TESTING  
Duration 
Procedure 
Screening portion 
2-2.5 hours 
Informed consent and assessment 
battery 
30 minutes 
Blood draw from nurse from Research 
Nexus  
Laboratory portion 
Minute 0 
Baseline measurement #1 (VAS, HR, 
BP, cortisol) 
Minute 5 
Baseline measurement #2 (VAS, HR, 
BP, cortisol) 
Minute 10 
Oxytocin or placebo administered 
Minute 40 
Post-medication assessment (VAS, 
HR, BP, cortisol) 
Minute 45 
Alcohol Cue  
Minute 50 
Post-Cue assessment (VAS, HR, BP, 
cortisol) 
Minute 65 
TAP 
Minute 70 
Immediate post-task assessment 
(VAS, HR, BP, cortisol) 
Minute 85 
15-minute post-task assessment (VAS, 
HR, BP, cortisol) 
Minute 100 
30-minute post-task assessment (VAS, 
HR, BP, cortisol) 
Minute 130 
60-minute post-task assessment (VAS, 
HR, BP, cortisol) 
Minute 135 
Participant debriefed, compensated 
and discharged 


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our waiting room until the rating subsides. Participants will be re-assessed in the waiting room 
every 5-10 minutes, and contacted by phone later that day by the PI to check-in.  
 
Debriefing Procedure. Because this study involves an element of deception, it is important that 
participants receive a debriefing as soon as the experiment is concluded. We do not want 
participants believing for any extended period of time that they shocked their intimate partner or 
received shocks from their intimate partner. Dr. Parrott’s extensive experience conducting TAP 
research among individuals and couples is that participants are well able to understand the nature 
and necessity of the deception employed in the TAP procedure. In the debriefing, participants will 
be told that their intimate partner was not actually engaged in the experimental tasks, that at no 
time during the procedure did they actually administer an electric shock to their partner, and that 
their responses were “normal” and consistent with those of others in the study.  They will also be 
informed that they were not told, at the beginning of the study, that the TAP measures aggression 
because many people artificially alter their responses if they are aware of this information.  Dr. 
Parrott has used these debriefing procedures in prior research projects that used a variety of 
interpersonal provocations without incident. To mitigate the likelihood that participants may feel 
intellectually inadequate because they were deceived by any manipulations, they will be told that 
90-95% of the participants in comparable projects are similarly deceived (this is a conservative 
average deception rate of similar laboratory aggression studies in Dr. Parrott’s laboratory) and 
that being deceived is completely “normal.”  Questions and concerns will then be addressed by 
the PI.   
 
Participant Compensation. Participants will receive $25 for the baseline assessment and $125 
for the laboratory portion of the study, totaling $150 per participant. Each participant will receive 
an additional $25 if they arrive on time to their original appointment.  
 
Participants who have obstacles to participation due to transportation will be offered taxi, bus 
pass, or mileage compensation.  
 
3.0 
Specimen Collection and Banking 
 
Blood and saliva samples will be collected from participants in this study for the purpose of 
examining cortisol and endogenous oxytocin. Saliva will not be collected from participants with a 
BMI of ≥39 or from participants with an appointment start time later than 10:00am. Blood will be 
drawn by MUSC Research Nexus nursing staff, processed, and stored at the MUSC Research 
Nexus until ready for assay. Saliva will be collected by trained research staff only and transported 
to the MUSC Research Nexus for processing, storage, and assay. Only approved study staff will 
have access to data associated with specimens. 
Note that saliva and/or blood samples may not be collected if the study team determines a 
contraindication exists that might affect study results (including recent consumption of caffeine or 
food, medications that affect oxytocin (e.g., androdgel, levothyroxine, etc.) or other factors). 
 
 
12.0 Data Management and Statistical Analysis Plan 
 
Descriptive statistics will be used to characterize participants at each time point.  Because 
the units of randomizations are dyads (i.e., couples), all analyses will account for potential within-
dyad correlation (e.g., intraclass correlation [ICC]). Generalized linear mixed models (GLMMs) 
with random couple effects will be used to assess group differences in baseline characteristics. 
These can be operationalized using SAS Proc Mixed and Proc GLIMMIX. Should any variables 


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exhibit significant departures from normality, variable transformations (e.g., logarithmic) or non-
parametric approaches will be used, as appropriate. GLMMs are ideal for handling analyses 
involving correlated measures108, and they will allow us to estimate both the between- and within-
couple variation.  GLMMs are also useful for modeling longitudinal (repeated) outcomes on 
individual subjects, and the models can be adapted with appropriate link functions for continuous, 
binary, and count outcomes. GLMMs will be constructed for analyses involving group (or 
subgroup) comparisons over time. The models will also control for relevant covariates, including 
baseline outcome levels and number of standard drinks during the 60 days prior to participation. 
Various covariance structures (e.g., compound symmetry, autoregressive, etc.) will be tested, with 
final model selection based on fit statistics such as Akaike Information Criterion109.  Analyses will 
be conducted using SAS v9.4 (Cary, NC).  
 
Hypothesis 1: Participants who receive oxytocin, as compared to placebo, will demonstrate 
significantly lower craving, aggression, physiological (HR, BP), and neuroendocrine (cortisol) 
reactivity to the TAP. To test this hypothesis, GLMMs with identity link functions (for continuous 
measures) and log link functions (for count data) will be used to model the between-group 
differences.  Random couple effects will be used to account for within-couple correlation. 
 
Hypothesis 2: Oxytocin response will be greater among women as compared to men. To test this 
hypothesis, GLMMs will be used to assess serially measured time points following medication 
administration (15, 30, and 60 minutes post task). The effects of gender, time, and their interaction 
will be assessed. Primary outcomes include alcohol craving, aggression, and cortisol. 
 
Hypothesis 3: Oxytocin response will be lower among individuals with higher endogenous 
oxytocin levels and greater IPA severity. To test this hypothesis, alcohol craving, aggression, and 
cortisol levels will be examined as repeated measures variables using the strategies described 
above. Separate models will be conducted for endogenous oxytocin levels and IPA severity. 
 
Randomization. Participants will be randomized to oxytocin or placebo. Because the 
extant literature suggests that the frequency and intensity of aggression in the TAP may be higher 
in men, on average, than women, a stratified randomization scheme will be used to ensure that 
groups are balanced by gender. 
 
Sample Size Justification. Given the preliminary nature of this investigation, we aim to 
detect between-group differences in aggression measured by the TAP (oxytocin vs. placebo).  
Prior work110-112 suggests that mean baseline aggression as measured within the TAP ranges 
from 2 to 4, with a standard deviation of 1.1 and with men having higher scores, on average, than 
women. With 50 couples (n=100) per group (and assuming alpha=0.05 and 2-sided hypothesis 
testing), we will have 80% power to detect moderate within-group changes (around 0.4 units 
[±10%-20%] on the TAP shock intensity scale), consistent with our study hypotheses.  We will 
have 80% power to detect moderate between-group differences (0.4 units) but with a larger alpha 
level (0.25), which is consistent with our pilot study framework.  
 
Confidentiality and Data Security. All research personnel will attend a required in-
service training conducted by Dr. Flanagan and Dr. Back where the screening, informed 
consent, and assessment protocols will be described. The study protocol and safety plan will be 
printed and kept in a central location within the research space for easy access for all research 
staff. Standard operating procedures (SOPs) for the management of any participant or study-
related emergency will be established and research staff will be trained on these protocols. All 
participant assessments will be scheduled during normal working hours beginning at 8am on 
the MUSC campus to ensure the presence of clinical staff and the safety of participants and 


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research staff. To protect participant confidentiality, all data will be stored in locked filing 
cabinets within a locked office and on MUSC’s encrypted computers and data servers. All 
participants will be assigned a numerical study identifier to minimize 
the potential to link 
identifying information with study data. One master list of study participants will be kept 
separate from all other study data. Access to data will be restricted to research staff. Data will be 
maintained in a manner consistent with IRB-approved protocol. Only de-identified data will 
be used to present findings in presentations or publications. All research staff have or will 
complete the University of Miami CITI training course in the responsible conduct of research. 
 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects  
Data and Safety Monitoring Plan. This section is based on the recommendations in NIAAA’s 
“Data 
and 
Safety 
Monitoring 
Guidelines”: 
http://www.niaaa.nih.gov/ResearchInformation/ 
ExtramuralResearch/ResourcesAppGrantees/guidelines.htm. 
 
Summary of the Protocol. The proposed study will examine the ability of oxytocin to reduce 
alcohol craving and aggression among individuals with a substance use disorder and co-
occurring intimate partner aggression (IPA), and identify predictors of oxytocin response (e.g., 
gender, endogenous oxytocin, IPA severity). The primary outcomes in this study include a 
reduction in (1) alcohol craving, (2) aggression, and (3) subjective, physiological, and 
neuroendocrine reactivity to a laboratory task (i.e., modified Taylor Aggression Paradigm). 
 
Trial Management. Dr. Flanagan (PI) will be responsible for monitoring the study. The study will 
be managed from the Addiction Sciences Division within the Department of Psychiatry and 
Behavioral Sciences at the Medical University of South Carolina (MUSC), College of Medicine, 
Charleston, SC. 
 
Regulatory Issues.  
 
(1) 
The DSM plan must designate an experienced, qualified professional (usually the PI) who 
can distinguish a serious adverse event (SAE) from a non-serious adverse event (AE) and 
an unanticipated problem. 
 
Drs. Flanagan (PI) and Back (primary mentor) will be responsible for distinguishing 
between serious (SAEs) and non-serious adverse events (AEs), and determining study 
relatedness. Potential AEs and SAEs will be identified during the study via self-report data, 
as well as assessments and interviews. All unexpected AEs and SAEs will be monitored 
until resolved. A detailed summary of all AEs will be prepared weekly by the research staff 
and reviewed by the PI at the weekly study team meeting.  
 
An Adverse Event (AE) is defined as any unwanted change, physically, psychologically or 
behaviorally, that occurs in a study participant during the course of the study that may or 
may not be related to study participation. AEs are reportable if the AE is unexpected AND 
related or possibly related AND serious or more prevalent than expected. The IRB definition 
of unexpected is that the AE is not identified in nature, severity or frequency in the current 
protocol, informed consent, investigator brochure or with other current risk information. The 
definition of related is that there is a reasonable possibility that the adverse event may have 
been caused by the drug, device or intervention. All AEs are reviewed weekly by the PI, 
and annually by the Data and Safety Monitoring Board (DSMB), MUSC IRB, and VA R&D. 
A Serious Adverse Event (SAE) is defined as an adverse event that has one of the following 
outcomes: results in death, is life-threatening, requires inpatient hospitalization or 


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prolongation 
of 
existing 
hospitalization, 
results 
in 
persistent 
or 
significant 
disability/incapacity, is a congenital anomaly/birth defect, OR requires intervention to 
prevent one of the above outcomes.  
 
(2) 
This experienced, qualified professional may be the PI, an independent investigator, or a 
team of experts. 
 
Dr. Flanagan (PI) will consult with Dr. Back (Primary Mentor) to identify and determine AE 
severity. 
 
(3) 
The DSM plan must indicate that serious adverse events and unanticipated problems will 
be reported to the local IRB, VA R&D, and to the NIAAA project officer within 48 hours. 
 
AEs and SAEs occurring during the course of the trial will be collected, documented, and 
reported in accordance with protocol and IRB reporting requirements. Adverse Events (AEs) 
that meet criteria for reportable AEs will be reported to all regulatory entities including the 
local IRB, VA R&D, and NIAAA project officer within 48 hours. SAEs will be reported within 
24 hours. All research staff involved with adverse event reporting will receive training 
including identification, evaluation, and documentation and reporting.  
 
(4) 
The DSM plan must indicate that an annual report will be submitted to the NIAAA Project 
Officer summarizing all adverse events. 
 
An annual report of all adverse events will be submitted annual to the NIAAA Project Officer. 
In addition, AEs will be reviewed weekly by Drs. Flanagan and Back, and annually by the 
Data Safety Monitoring Board (DSMB) and local IRB. Any significant actions taken by the 
local IRB, VA R&D, and protocol changes will be reported to NIAAA.  
 
(5) 
The DSM plan must specify that female subjects who are pregnant, nursing, or not using 
effective methods of birth control will be excluded from studies involving the administration 
of alcohol and/or drugs. 
 
The proposed study does not involve alcohol or drug administration. However, women who 
are pregnant or breastfeeding are not eligible to participate in the proposed study due to the 
known effects of the study drug (oxytocin) on parturition and lactation. 
 
(6) 
The DSM plan must indicate that trained personnel will be present or on call when human 
laboratory studies of alcohol or other drug intake are conducted. 
 
Dr. Flanagan (PI) and/or Dr. Back (primary mentor) will be present or on call at the time of 
all study visits including the human laboratory visit. 
 
(7) 
The DSM plan must indicate the follow up plans for serious adverse events and 
unanticipated problems. 
 
For any SAE, the appropriate SAE protocol specific reporting forms will be completed and 
disseminated to the appropriate persons and within the designated timeframes as indicated 
above. If complete information is not available when the initial 24-hours that the SAE report 
is disseminated, follow-up information will be gathered to enable a complete assessment 
and outcome of the event. This information may include hospital discharge records, autopsy 


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reports, clinic records, etc. The research staff will attach copies of source documents to the 
SAE report for review by Drs. Flanagan and Back and for forwarding to the NIAAA Program 
Officer. In addition, the PI will provide a signed, dated SAE summary report, which will be 
sent to the NIAAA Medical Safety Officer within 2 weeks of the initial SAE report. Follow-up 
of all unexpected and serious AEs will be reported to all regulatory entities including the 
local IRB, DSMB, and NIAAA. For each AE/SAE recorded, the research staff will follow 
the AE/SAE until resolution, stabilization, or until the subject is no longer in the study. 
 
(8) 
For studies in which alcohol is administered, the DSM plan must indicate that NIAAA 
guidelines for the administration of alcohol will be followed. These guidelines can be found 
at 
the 
following 
web 
address: 
http://www.niaaa.nih.gov/research/guidelines-and-
resources/administering-alcohol-human-studies. 
 
The proposed study does not involve alcohol administration. 
 
(9) 
If the study has a follow-up phase, there must be a specific plan for referral to treatment 
during follow-up of any patient requiring additional intervention due to significantly 
increased alcohol consumption or serious psychiatric/medical symptoms. 
 
The proposed study takes place during one study visit and does not include a follow-up 
phase. All participants will be provided with a list of community resources upon study 
completion. Ineligible individuals presenting with serious mental or physical health 
symptoms including acute alcohol withdrawal will be referred clinically. 
 
(10) The DSM plan must indicate that all adverse events and unanticipated problems during 
follow-up will be reported (SAEs within 48 hours) to the IRB and NIAAA. 
 
Not applicable, as the proposed study does not include a follow-up phase. 
 
(11) The DSM plan must briefly describe the procedures for data quality assurance and 
confidentiality. 
 
A data analytic plan is outlined in the Data Analysis section. Because this study is a 
preliminary test of a new medication, we are interested in examining a broad range of 
outcome variables. The main outcome variables include alcohol craving, aggression, and 
subjective, physiological, and neuroendocrine reactivity to the laboratory procedure. 
Outcome data will be analyzed using chi-square, ANCOVA, and Poisson regression 
models. The alpha level for statistical significance will be set at .05. 
 
Data quality will be monitored by random inspection of completed assessment forms by 
research staff. Dr. Flanagan and a statistician will examine the outcomes database for 
missing data, unexpected distributions or responses, and outliers. Any problems with the 
assessment process, data collection, or data entry will be discussed between Drs. 
Flanagan and Back. Study procedures will follow the FDA’s Good Clinical Practice 
Guidelines (www.fda.gov/oc/gcp). Confidentiality will be maintained during all phases of the 
study. Any outside requests for information or any breaches in confidentiality will be 
reported to Dr. Flanagan. All requests by subject’s physicians and other medical providers 
will be referred directly to applicant. No names or other identifying information will be 
included on any source documents. Only a subject identification number will be used on 
source documents. All data will be kept securely in a locked cabinet in a locked office.  


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(12) Phase III clinical trials must have an independent data and safety monitoring board.  Phase 
I and II studies that have multiple clinical sites, are blinded or employ particularly high risk 
interventions or vulnerable subjects may require a DSMB at the discretion of NIAAA. 
 
The proposed study meets the definition of a phase II clinical trial in that (a) oxytocin has 
an established dosing range, (b) it will be conducted among 100-300 individuals, and (c) 
examines efficacy of oxytocin for a specific purpose (e.g., to reduce alcohol craving and 
IPA). We will create a DSMB to monitor overall participant safety, the rate and severity of 
adverse events, and the validity and integrity of the data. The panel includes 2 researchers 
with experience in treating patients with alcohol use disorders and IPA  and a statistician. 
The board may be called at any point if needed for unexpected AEs, etc. Modifications 
will be made in the procedures and/or the protocol if necessary based on the 
recommendations of the board. A DSMB report will be filed with the IRB on a yearly 
basis, unless greater than expected problems occur. The report will include subject 
characteristics, retention and disposition of study subjects, quality assurance issues and 
reports of AEs, significant/unexpected AEs and serious AEs. Results will be reported at the 
end of the trial.  
 
ClinicalTrials.gov Requirements: In accordance with Public Law 110-85, the proposed trial will be 
registered with ClinicalTrials.gov. Applicable requirements regarding results reporting will be 
adhered to. 
 
14.0 Withdrawal of Subjects  
 
This is a cross-sectional study. All participants will be screened thoroughly for eligibility following 
informed consent. The PI may discontinue participation at any time if a participant demonstrates 
or reports significant distress, presents a risk of harm to self or others, or is otherwise unable to 
complete the study.  Participants may withdraw from participation at any time during the study 
procedure. Clinical referrals to community resources will be provided to all study participants. 
 
15.0 Risks to Subjects 
 
Potential Risks. Risks associated with this study include discomfort associated with (1) TAP 
participation (e.g. psychological and physical discomfort), (2) oxytocin self-administration, (3) 
alcohol cue procedures, (4) discomfort from being deceived, and (5) risk of aggression during and 
after completion of study procedures. Procedures using the TAP may result in psychological or 
physical distress. Participants may experience distress related to reporting IPA or engaging in 
the laboratory aggression task. Based on the research team’s past experience and available 
literature the risks involved in the proposed project are minimal and manageable7,131. Dr. 
Parrott (consultant) has tested approximately 2,000 participants (sober and intoxicated) using the 
TAP without a single adverse event to date. With respect to the receipt and ostensible 
administration of mild electric shocks during the TAP, it is important to note that this task has been 
shown to be a safe measure of aggression in over 100 studies83,132-134.   
Risks associated with oxytocin administration have been noted among women given 
intravenous, but not intranasal, oxytocin for its FDA-approved purpose to induce labor and 
facilitate lactation135,136. These risks include seizures, mental disturbances, nausea, vomiting, 
irregular heartbeat, high blood pressure, and unexpected bleeding or contraction of the uterus 
and have been observed in a small number of women99. However, preliminary studies 


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conducted by our group and others indicate that risks of intranasal oxytocin administration 
at the planned dose of 40 IU is minimal and manageable through the proposed human subjects 
protection methods. Our group has administered intranasal oxytocin at this dose to over 200 
research participants to date without a single adverse event reported. 
Participants will be screened for acute alcohol withdrawal at the outset of the study. 
Participants reporting CIWA-Ar scores >8 will be excluded from participation and referred 
clinically. All possible efforts to minimize participant burden and distress will be made. All 
possible efforts will be made to protect the confidentiality of participants’ data, except in the 
event of imminent risk to self or others, or in the event of disclosure of child or elder abuse. In 
the event that confidentiality must be broken to protect the safety of participants or others, only 
the data essential to make an adequate report to authorities will be disclosed. All participants 
will review the IRB-approved informed consent document with research staff in a private room 
separate from their partner. Through this process, research staff will inform all research 
participants of the risks of participation, including emotional distress. In the event that a 
participant experiences substantial distress or reports risk of harm to oneself or others, they 
will be asked to complete a safety plan. The Mobile Crisis Unit of Charleston County and 
urgent care services on the MUSC campus and at the Charleston VAMC are additional resources 
available to study staff and research participants. Dr. Flanagan and her mentor (Dr. Back) 
are licensed clinical psychologists equipped to help participants manage distress and to 
evaluate conditions in which participants need additional assistance. In the event that a 
participant becomes distressed during or following an assessment, I will contact the participant 
later that day to check-in and the following day to ensure they have received necessary 
resources, and to assess their safety and welfare. In the event that any serious adverse event 
occurs resulting from study participation, that event will be reported in writing to the MUSC 
IRB and NIH within 24 hours. In similar past and ongoing studies, these resources have been 
sufficient to manage problems or distress related to participation. 
Furthermore, it is possible that participants will experience psychological discomfort as a 
result of being deceived.  Deception will be used in the proposed study in relation to the TAP.  
Participants cannot be told that the true purpose of the study is to measure aggression toward an 
intimate partner.  Informing participants of this fact may elicit artificial socially desirable (non-
aggressive) responses. Instead, participants will be told that they will be competing in a reaction-
time task against their intimate partner in a nearby room. In actuality, there is no opponent (and 
therefore no competition). This deception exists to create the impression of an adversarial 
interpersonal interaction and is required to increase the ecological validity of the study. 
It is possible that participation in this study may “prime” some participants to behave 
aggressively toward an intimate partner or another person after leaving the laboratory. Given that 
the long-term goal of this research project is to inform interventions designed to prevent IPA, it is 
essential that participants (a) not experience an increased risk for IPA as a function of participating 
in this project, and (b) be afforded all available protections and services to reduce this risk. 
Although we do not anticipate increases in the risk of physical safety of male or female partners 
due to participation in this study, we have nonetheless included procedures to mitigate these risks 
and to help ensure their safety.  In order to reduce the already minimal probability of aggression 
between intimate partners in the laboratory following the conclusion of the TAP, researchers will 
conduct individual debriefing sessions separately for the participant and the partner. Thus, when 
the couple reunites at the conclusion of study procedures, participants will be aware that it was 
not actually the partner against which they were playing during the TAP, and the partner will be 
aware that the participant was led to believe that he/she was the opponent during the game. If, 
for any reason, the partner expresses any fear or concern about reuniting with the participant, all 
necessary and practical steps for intervention will be taken. Towards this end, we will conduct all 
screenings and consent discussions without partners present, thus reducing the likelihood that 


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participants are coerced into participating. In addition, we have created multiple measures to 
maintain the confidentiality of partner responses, including not sharing any partner information 
with the male/female index participant. Also, we will further manage this risk by excluding couples 
that report acts of severe IPA (as defined by the CTS-2) during screening. 
 
Managing Participant Safety and Risk. Risks of participation will be outlined in the informed 
consent and reviewed during the informed consent procedure. If severe forms of IPA are 
reported, the PI will discuss the situation with participants privately and will engage in safety 
planning and offer referrals to shelters and additional counseling as appropriate. Severe 
physical and sexual violence is defined as endorsing any of the following items from the Severe 
Violence subscale on the CTS-297: used a knife or gun, punched or hit with something that 
could hurt, choked, slammed against a wall, beat up, burned or scalded on purpose, kicked, 
used force or threats to make my partner have oral or anal sex, used force or threats to make 
my partner have sexual intercourse. The PI will follow up with participants if other forms of severe 
violence are disclosed during interviews with research assistants or study personnel. As in all of 
our studies, we will vigilantly monitor these issues to protect the safety of study participants. 
The laboratory procedure may induce some psychological or physical discomfort. 
However, it is unlikely that participants will incur any additional risk above that experienced in 
their daily lives. Prior to the aggression testing, participants will be told that if they feel that 
the TAP shocks are too high, they can either ask the PI to reduce the intensity (through an 
intercom) or quit the study at no penalty and receive partial payment. Dr. Parrott (consultant) 
and colleagues surveyed over 400 men immediately after completing the TAP and one week 
later.  He found that an extremely small proportion (1.8%) of participants reported an 
increased likelihood of behaving aggressively as a result of participation. These participants 
denied any specific plans of action and reported one-week later that these feelings did not 
persist. No participant or partner reported that involvement in the research led to any 
increased tendencies towards aggression, and no adverse events were reported. Because 
interview and self-report assessment measures cover topics of a sensitive nature, participants 
will have the option to decline answering any questions they prefer not to answer. Participants 
will be informed during the informed consent procedure that no third party, including their 
partner, will have access to assessment responses with the standard exceptions in the event 
of suspected or reported child or elder abuse, or risk of harm to self or others. All couples will 
be debriefed by the study team following the experimental procedure including full disclosure of 
the study’s purposes and procedures. Dr. Flanagan will follow up with any distressed participants 
later that day via phone and will provide clinical referrals as necessary. 
Participants will be informed about the potential side effects of intranasal oxytocin and 
will be closely monitored by the research team. Oxytocin administration will occur in a fully-
staffed clinical environment equipped with ready access to clinicians and emergency care if 
necessary. 
Participants may also experience elevated craving following the laboratory procedure. If 
a participant experiences elevated craving as a result of participation in the proposed study, 
they will be encouraged to meet with Dr. Flanagan or her primary mentor, who are licensed 
clinical psychologists with extensive experience working in research and clinical settings with 
high-risk populations. The study procedure includes monitoring subjective craving ratings at 
regular intervals (15, 30, and 60 minutes) post-task. Thus, we are well equipped to detect 
persistent elevations in craving or other negative affect. Any subject reporting a >5 on the 
craving scale will be asked to sit in the waiting room and look at magazines. Their craving and 
distress level will be re-assessed by research staff every 5-10 minutes during this time. Subjects 
will be asked to remain in the waiting room until their craving is <5. Dr. Flanagan will also 
call the subject later that day to check-in. Finally, clinical referrals to local treatment centers 


Version 23; 11.13.2020 
 
Page 18 of 27 
 
will be provided to all subjects. Participants will also have access to emergency psychiatric 
services at MUSC. Dr. Flanagan and her team of mentors have implemented these methods 
successfully in previous and ongoing studies conducted by Dr. Back and other faculty at MUSC 
involving subjects with AUD and co-occurring problems. In addition, previous studies at MUSC 
that involve stress or craving induction among individuals with AUD suggest that participation is 
associated with decreased, not increased, substance use in the month after completing the 
laboratory stress and cue tasks11,12. 
Dr. Flanagan and her primary mentor will meet weekly to review study procedures and 
progress and any clinical issues arising with participants. Dr. Flanagan will implement a Data 
and Safety Monitoring Board (DSMB) which will meet annually to review any adverse events 
associated with study participation. Dr. Flanagan has completed formal training in the 
responsible conduct of research and will continue to maintain institutional compliance 
requirements. 
 
16.0 Potential Benefits to Subjects or Others 
 
Alcohol is a significant contributing cause of IPA, and extant literature strongly indicates the need 
to (1) develop clear and testable models of IPA etiology and maintenance, and (2) elucidate 
possible mechanisms through which this social malady can be prevented or reduced.  Preclinical 
and preliminary human data suggest that oxytocin has potential to influence treatment in the 
field of AUD and human aggression. The health burden associated with AUD and IPA, both 
individually and collectively, is tremendous in the U.S. and globally. Despite the limited treatment 
response  to  behavioral  intervention  for  these  commonly  co-occurring  problems,  research 
investigating pharmacological interventions to improve intervention is scant. The present study 
is the first to investigate the utility of oxytocin to reduce alcohol craving, aggression, and 
subjective, physiological, and 
neuroendocrine reactivity to a well-controlled aggression 
paradigm. The use of oxytocin as a supplement to behavioral interventions, particularly those 
addressing AUD and commonly co-occurring problems such as IPA, present the potential for a 
highly efficient and cost-effective way to meet the treatment needs of individuals and couples 
nationwide. 
 
17.0 Sharing of Results with Subjects 
 
Study data will not be shared with participants to maintain confidentiality. 
 
 
 
18.0 Drugs or Devices  
 
The IND for oxytocin’s use in this study is held by Dr. Flanagan. Oxytocin will be compounded, 
stored, and dispensed by Investigational Drug Services (IDS) on the MUSC campus or Pitt 
Street Pharmacy in Mt. Pleasant, SC. Pitt Street Pharmacy is a compounding pharmacy used by 
many other MUSC clinical trials, including others within our group. Pitt Street Pharmacy is also a 
member of The International Academy of Compounding Pharmacists (IACP). IACP is an 
international, non-profit association protecting and promoting the art and skill of pharmaceutical 
compounding.  
 
 
 


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