Hybrid Closed-Loop Control With Prandial Insulin Dosing Informed by Insulin Sensitivity in Adolescents With Type 1 Diabetes
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: University of Virginia

 
U V A C E N T E R F O R DI A B E T E S T E C H N OL O G Y  
 
 
1 
Hy bri d Cl os e d -Lo o p C o ntr ol wit h Pra n di al 
2 
I ns uli n D osi ng I nf or m e d by I ns uli n S e nsitivity 
3 
i n A d ol esc e nts wit h Ty p e 1 Di a b et es 
4 
 
5 
 
6 
 
7 
 
8 
Pr ot oc ol C h air  
9 
C hi ar a F a bris, P h D   
1 0  
U ni v ersit y of Vir gi ni a  
1 1  
C e nt er f or Di a b et es T ec h n ol o gy  
1 2  
 
1 3  
 
1 4  
 
1 5  
N C T 0 4 8 7 8 1 2 0  
1 6  
V ersi o n N u m b er: v 2. 4 
1 7  
1 4 -A p r-2 0 2 2  
 
1 8  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 of 6 6  
 
K E Y R OL E S  
1 9  
Pr ot oc ol Pri nci p al I n v esti g at or  
N a m e, d e gr e e  
C hi ar a F a bris, P h D  
I nstit uti o n N a m e 
U ni v ersit y of Vir gi ni a C e nt er f or Di a b et es T ec h n ol o g y  
St u d y M e dic al I n v esti g at or  
 
N a m e, d e gr e e  
M eliss a Sc h o el w er, M D  
I nstit uti o n N a m e 
U ni v ersit y of Vir gi ni a  
 
 
2 0  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 of 6 6  
 
P R O T O C OL V E R SI O N HI S T O R Y  
2 1  
V ersi o n 
N u m b er  
A ut h or(s)  
A p pr o v er  
Eff ecti v e D at e  
R e visi o n D escri pti o n  
1. 0  
M eliss a 
Sc h o el w er  
C hi ar a F a bris  1 1 -M ar -2 0 2 1  
Ori gi n al Pr ot oc ol  
1. 1  
M ar y Oli v eri  
C hi ar a F a bris  2 9 -M ar -2 0 2 1  
F D A M o dific ati o ns:  
•  I/ E m o dific ati o ns 
(s ecti o n 3. 4  & 3. 5 ) 
•  A 1c  l o w er li mit 
•  E n glis h pr ofici e ncy  
•  A d diti o n al 
r estricti o ns of m e ds 
d uri n g st u d y 
•  A d di ti o n al m e dic al 
iss u es 
•  Cl arifi e d i ns uli n 
p u m p tr ai ni n g 
(s ecti o n 5. 2 ) 
•  C orr ect e d C G M 
arri v al v al u e s 
(s ecti o n 6. 2  & 6. 3 ) 
•  A d d e d M e al 
R e q uir e m e nt t o 
Pil ot st u d y (s ecti o n 
6. 5 ) 
•  Cl arifi e d disc h ar g e 
v al u es of C G M 
r e a di n g is ≤2 5 0 
m g/ dL a n d k et o n es 
< 0. 6 m m ol/L 
(s ecti o n 6. 7  a n d 
8. 5 ) 
•  A d d e d A d missi o n(s)  
Disc h ar g e & P ost -
St u d y C h eck I n Visit 
d escri pti o n (s ecti o n  
8. 5  & 8. 6 ) 

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 of 6 6  
 
•  A d d e d a d diti o n al 
p ossi bl e 
occ ur r e nc es of 
C O VI D -1 9 t ests 
(s ecti o n 9. 1. 3 ) 
•  A d d e d p ositi v e 
C O VI D -1 9 
s y m pt o ms (s ecti o n 
1 0. 3. 1 )  
•  A d d e d p artici p a nt 
st o p pi n g crit eri a of 
p ositi v e C O VI D -1 9 
t est (s ecti o n 
1 1. 1 0. 1 ) 
1. 2  
M ar y Oli v eri  
C hi ar a F a bris  0 1 -A pr -2 0 2 1  
F D A M o dific ati o ns:  
•  R e m o v e d ‘if 
k et o n es w er e 
pr es e nt at ti m e  of 
disc h ar g e’ (s ecti o n 
6. 7  a n d 8. 5 ) 
1. 3  
J o n Ols o n 
M ar y Oli v eri  
C hi ar a F a bris  0 3 -M a y -2 0 2 1  
I R B F ull B o ar d M o ds:  
•  C h a n g e d 1 -2 pil ot 
p artici p a nts t o u p 
t o 3 p artici p a nts 
•  R e vis e d St atistic al 
(s ecti o n 1 3. 3. 2 ).  
1. 4  
M ar y Oli v eri  
C hi ar a F a bris  
M eliss a 
Sc h o el w er  
2 5- J u n-2 0 2 1  
St u d y T e a m m o ds:  
•  A d d e d c o p y of 
C o vi d v acci n ati o n 
r ec or d if a v ail a bl e 
(s ecti o n 3. 4 ). 
•  M o difi e d C o vi d 
p olicy (s ecti o n 
1 0. 3 ).  
2. 0  
C hi ar a F a bris  
C hi ar a F a bris  1 6 -A u g -2 0 2 1  
St u d y T e a m m o ds:  
•  R e vis e d Pr ot oc ol 
S u m m ar y T a bl e t o 
i ncl u d e c h a n g e i n 
st u d y fr o m a 6 d a y  
c a m p t o a t w o 4-

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 of 6 6  
 
d a y c a m p st u d y  
(Pr ot oc ol S u m m ar y , 
s ecti o n 1. 3 , Fi g ur e 
1 , 5. 1 , 8. 4. 4 ) 
•  H e m o gl o bi n A 1 C 
P O C will b e 
c oll ect e d at t h e first 
st u d y a d missi o n 
(T a bl e 1 )  
•  Cl arifi e d t h at st u d y 
is ex a mi ni n g  
i ncr e as e d p h ysic al 
acti vity a n d 
ex ercis e  ( a er o bics) 
i n T 1 D M 
a d ol esc e nts 
(s ecti o n 1. 1 , 1. 2 , 
1. 3 ) 
•  S p ecifi e d us e of 
D exc o m G 6 C G M 
(s ecti o n 1. 3 , 3. 4 ) – 
Pl e as e n ot e, t his 
us e of D exc o m G 6 
C G M (s ecti o n 1. 3, 
3. 4) w as n ot 
a p p r o v e d b y t h e 
I R B F ull B o ar d wit h 
t h e a p pr o v al of t h e 
ot h er v 2. 0 e dits.  
T h er ef or e, it w as 
r e m o v e d. 
•  A d d e d i ncl usi o n 
crit eri a t h at 
p artici p a nts m ust 
h a v e c o m pl et e d   
C O VI D -1 9 v acci n e 
at l e ast 2 w e e ks 
pri or t o st u d y 
a d missi o n(s)  a n d 
pr o vi d e t h e 

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 of 6 6  
 
v acci n ati o n c ar d 
(s ecti o n 3. 4 , 1 0. 3 ) 
•  A d d e d excl usi o n 
crit eri a of:  
•  K n o w n c o nt act wit h 
C O VI D -p ositi v e 
i n di vi d u al wit hi n 1 4 
d a ys of a n y st u d y 
a d missi o n(s)  
wit h o ut a n e g ati v e 
f oll o w-u p C O VI D 
t est p erf or m e d 3-5 
d a ys aft er t h e d at e 
of ex p os ur e  
•  S y m pt o ms of 
C O VI D -1 9 ( e. g., 
f e v er, s h ort n ess of 
br e at h, u n ex p ect e d 
l oss of t ast e or 
s m ell) d e v el o p e d 
wit hi n 1 4 of a n y 
st u d y a d missi o n(s)   
•  N o n -v acci n at e d 
p artici p a nts will b e 
excl u d e d fr o m 
p artici p ati o n 
(s ecti o n 3. 5 , 1 0. 3. 1 ) 
•  A d d e d t h at b as al 
r at e will b e re d uc e d 
1 0 -2 0 % b y st u d y 
p h ysici a n (s ecti o n 
5. 2. 1 ) 
•  Cl arifi e d  s p ecific 
C O VI D -1 9 
s y m pt o ms t h at t h e 
st u d y t e a m will as k 
at pr e -st u d y 
a d missi o n(s)  c h eck-
i n visits (s ecti o n 
8. 3. 1 ) 

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 7 of 6 6  
 
•  C O VI D -1 9 T est  
s ecti o n  e dit e d 
(s ecti o n 9. 1. 3 ) 
•  St u d y/c a m p st aff 
will b e f ull 
v acci n at e d (s ecti o n 
9. 1. 3 , 1 0. 3. 1 ) 
•  C O VI D -1 9 Ris k 
Miti g ati o n Pl a n a n d 
J ustific ati o n s ecti o n 
e dit e d (s ecti o n 
1 0. 3 ) 
•  St aff at C a m p 
H oli d a y Tr ails will 
w or k t o r e d uc e 
C O VI D ex p os ur e s b y 
f oll o wi n g t h e 
g ui d eli n es  i n t his 
pr ot oc ol (s ecti o n 
1 0. 3. 2 ) 
•  C O VI D -1 9  
Tr a ns missi o n 
s ecti o n e dit e d 
(s ecti o n 1 1. 4 ) 
•  Ot h er mi n or 
cl arific ati o ns m a d e 
t hr o u g h o ut 
d oc u m e nt.  
2. 1  
M ar y Oli v eri  
C hi ar a F a bris  2 1 -S e p -2 0 2 1  
I R B M o dific ati o ns:  
•  R e m o v e d 
r e q uir e m e nt o n us e 
of D exc o m G 6 C G M 
(s ecti o n 1. 3 , 3. 4 ) 
St u d y T e a m M o dific ati o ns:  
•  R e m o v e d r ef er e nc e 
t o Acc u-C h e k G ui d e 
gl uc o m et er  (s ecti o n 
2. 3 , 1 0. 1. 6 ) 
F D A M o dific ati o ns  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 8 of 6 6  
 
•  I ncr e as e d 
e nr oll m e nt of 3 5 
p e o pl e si g ni n g 
c o ns e nt t o 7 0 
p e o pl e si g ni n g 
c o ns e nt ( Pr ot oc ol 
S u m m ar y, 1. 4. 1 , 
3. 1 , 4. 2 ) 
•  R ei nstit ut e d C O VI D -
1 9 P C R t esti n g  4 8 -
7 2 h b ef or e c a m p 
f or p artici p a nts a n d 
st aff (s ecti o n 8. 2 ,  
9. 1. 3 ) 
•  P artici p a nts  wit h 
C O VI D -1 9 
s y m pt o ms will b e 
excl u d e d fr o m 
st u d y a d missi o n(s)  
(s ecti o n 8. 2 , 9. 1. 3 ) 
•  N o hi g h -ris k 
acti viti es r e q uiri n g 
s ust ai n e d cl os e 
c o nt act will b e 
c o n d uct e d (s ecti o n 
1 0. 3. 3 ) 
•  P artici p a nts wit h 
C O VI D -1 9 
s y m pt o ms will b e 
is ol at e d u ntil 
disc h ar g e d a n d will 
b e a d vis e d o n 
a p pr o pri at e 
is ol ati o n a n d  
t esti n g t o b e 
c o m pl et e d  (s ecti o n 
1 1. 4 ) 
•  Cl os e c o nt acts of a 
p artici p a nt wit h 
s y m pt o ms will b e 

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 9 of 6 6  
 
disc h ar g e d a n d will 
b e a d vis e d o n 
a p pr o pri at e 
is ol ati o n a n d 
t esti n g t o b e 
c o m pl et e d (s ecti o n 
1 1. 4 ) 
•  U ni v ers al m as ki n g 
a n d p h ysic al 
dist a nci n g will b e 
m a n d at e d f or t h e 
r e m ai ni n g 
p artici p a nts a n d 
st u d y st aff i n t h e 
e v e nt of a 
s y m pt o m atic c as e 
f or t h e r e m ai n d er 
of t h e st u d y 
a d missi o n (s ecti o n 
1 1. 4 ) 
2. 2  
M ar y Oli v eri  
C hi ar a F a bris  1 6- N o v -2 0 2 1  
St u d y T e a m m o ds:  
•  R e -i ns ert e d t h at 
c a m p m a y b e h el d  
o v e r 6 d a ys or t w o 
4- d a y c a m p 
a d missi o ns  (s ecti o n 
1. 3 ) 
2. 3  
M ar y Oli v eri  
M ar y Oli v eri  
0 2 -D ec -2 0 2 1  
I R B Pr e-R e vi e w :  
•  C orr ect e d  s essi o n 
wit h s essi o ns(s) 
t hro u g h o ut 
d oc u m e nt  
•  A d d e d  P artici p a nt 
A d missi o n Iti n er ar y 
f or 6 ni g ht/ 5 d a y 
a d missi o n.  
2. 4  
M ar y Oli v eri  
C hi ar a F a bris  2 5 _ M ar -2 0 2 2  
St u d y T e a m m o ds:  
•  P artici p a nts will 
sl e e p i n ca bi ns  
(s ecti o n 1 0. 3. 1 ) 

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 0  of 6 6  
 
•  R e vis e d C O VI D -1 9 
p olici es (s ecti o n 
3. 5 , 8. 2 , 8. 3 , 9. 1. 3 , 
1 0. 3 , 1 0. 3. 1 , 1 1. 4 ) 
•  R e m o v e d i nc orr ect 
D S M B r ef er e nc es ; 
r e pl ac e d wit h 
M e dic al M o nit or 
(s ecti o n 7. 1 , 7. 2 , 
C h a pt er 1 1: ) 
2. 5  
M ar y Oli v eri  
C hi ar a F a bris  1 4 -A pr -2 0 2 2  
F D A M o dific ati o ns  
•  P ost st u d y c h eck i n 
visit m o difi e d (s ecti o n 
1 1. 4 ) 
 
 
2 2  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 1  of 6 6  
 
SI T E P RI N CI P AL I N V E S TI G AT O R S T AT E M E N T O F C O M PLI A N C E  
2 3  
Pr ot oc ol Titl e:  Hy bri d Cl os e d -l o o p C o ntr ol wit h Pr a n di al I ns uli n D osi n g I nf or m e d b y I ns uli n 
2 4  
S e nsiti vit y i n A d ol esc e nts wit h Ty p e 1 Di a b et es  
2 5  
Pr ot oc ol V ersi o n: v 2. 5 
2 6  
Pr ot oc ol D at e:  1 4 -A pr -2 0 2 2  
2 7  
I h a v e r e a d t h e pr ot oc ol s p ecifi e d a b o v e. I n m y f or m al c a p acity as a Sit e Pri nci p al I n v esti g at or, 
2 8  
m y d uti es i ncl u d e e ns uri n g t h e s af et y of t h e st u d y p artici p a nts e nr oll e d u n d er m y s u p er visi o n . It 
2 9  
is u n d erst o o d t h at all i nf or m ati o n p ert ai ni n g t o t h e st u d y will b e h el d strictl y c o nfi d e nti al a n d 
3 0  
t h at t his c o nfi d e nti alit y r e q uir e m e nt a p pli es t o all st u d y st aff at t his sit e. 
3 1  
T his tri al will b e c arri e d o ut i n acc or d a nc e wit h I C H E 6 G o o d Cli nic al Pr actic e ( G C P) a n d as r e q uir e d 
3 2  
b y t h e f oll o wi n g: U nit e d St at es ( U S) C o d e of F e d er al R e g ul ati o ns ( C F R) a p plic a bl e t o cli nic al 
3 3  
st u di es ( 4 5 CF R P art 4 6, 2 1 CF R P art 5 0, 2 1 C F R P art 5 6, 2 1 C F R P art 3 1 2, a n d/ or 2 1 CF R P art 8 1 2).  
3 4  
As t h e  Pri nci p al I n v esti g at or, I will ass ur e t h at n o d e vi ati o n fr o m, or c h a n g es t o t h e pr ot oc ol 
3 5  
will  t a k e pl ac e wit h o ut pri or a gr e e m e nt fr o m t h e s p o ns or a n d d oc u m e nt e d a p pr ov al fr o m t h e 
3 6  
I nstit uti o n al R e vi e w B o ar d (I R B), or ot h er a p pr o v e d Et hics C o m mitt e e, exc e pt w h er e n ec ess ar y 
3 7  
t o eli mi n at e a n i m m e di at e h az ar d(s) t o t h e tri al p artici p a nts. 
3 8  
All k e y p ers o n n el ( all i n di vi d u als r es p o nsi bl e f or t h e d esi g n a n d c o n d uct of t his tri al) h a v e 
3 9  
c o m pl et e d H u m a n P artici p a nts Pr ot ecti o n Tr ai ni n g a n d G o o d Cli nic al Pr actic e Tr ai ni n g. F urt h er, I 
4 0  
a gr e e t o e ns ur e t h at all st aff m e m b ers i nv ol v e d i n t h e c o n d uct of t his st u d y ar e i nf or m e d a b o ut 
4 1  
t h eir o bli g ati o ns i n m e eti n g t h e a b o v e c o m mit m e nts. 
4 2  
 
 
4 3  
I n v esti g at or’s Si g n at ur e _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _D at e: _ _ _ _ _ / _ _ _ _ _ / _ _ _ _ _  
4 4  
I n v esti g at or’s N a m e: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
4 5  
Sit e N a m e:  U ni v ersit y of Vir gi ni a  
 
4 6  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 2  of 6 6  
 
LI S T O F A B B R E VI A TI O N S  
4 7  
A B B R E VI A TI O N  
D E FI NI TI O N  
A P  
Artifici al P a ncr e as  
B G  
Bl o o d Gl uc os e  
B T/ B TL E  
Bl u et o ot h, Bl u et o ot h l o w e n er g y  
C G M  
C o nti n u o us Gl uc os e M o nit ori n g  
CL C  
Cl os e d -L o o p C o ntr ol 
Ci Q  
T a n d e m t:sli m X 2 I ns uli n P u m p wit h C o ntr ol -I Q T ec h n ol o g y 
C SII  
C o nti n u o us S u bc ut a n e o us I ns uli n I nj ecti o n  
D K A  
Di a b etic K et o aci d osis  
D S M B  
D at a S af et y M o nit ori n g B o ar d  
F D A 
F o o d a n d Dr u g A d mi nistr ati o n  
G C P  
G o o d Cli nic al Pr actic e  
H b A 1c  
H e m o gl o bi n A 1c  
H B GI  
Hi g h Bl o o d Gl uc os e I n d e x  
H CL  
H y bri d cl os e d -l o o p 
I D E 
I n v esti g ati o n al D e vic e E x e m pti o n 
I O B 
I ns uli n-o n -B o ar d  
I S 
I ns uli n s e nsiti vit y  
J D R F 
J u v e nil e Di a b et es R es e arc h F o u n d ati o n  
L B GI 
L o w Bl o o d Gl uc os e I n d e x  
NI H  
N ati o n al I nstit ut es of H e alt h  
P O C  
P oi nt -of -C ar e  
S A P  
S e ns or -A u g m e nt e d I ns uli n P u m p  
Q C  
Q u alit y C o ntr ol  
UI  
Us er I nt erf ac e  
 
 
4 8  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 3  of 6 6  
 
P R O T O C OL S U M M A R Y  
4 9  
P A R TI CI P A N T A R E A  
D E S C RI P TI O N  
Titl e  
Hy bri d Cl os e d -l o o p C o ntr ol wit h Pr a n di al I ns uli n 
D osi n g I nf or m e d by I ns uli n S e nsiti vit y i n A d ol esc e nts 
wit h Ty p e 1 Di a b et es  
I n v esti g ati o n al D e vic e 
S m art b ol us c alc ul at or i nf or m e d by i ns uli n s e nsiti vit y 
(SI ) 
O bj ecti v es  
T h e o bj ecti v e  of t his st u dy is t o e v al u at e t h e s afety a n d 
f e asi bility of  a  s m art  b ol us  c alc ul at or  th at  a dj usts  
i ns uli n  d osi n g f or m e als acc or di n g t o r e al -ti m e  SI i n 
a d ol esc e nts wit h t y p e 1 di a b et es ( T 1 D ) usi n g a hy bri d 
cl os e d l o o p s yst e m d uri n g a n acti v e  w e e k of di a b et es 
c a m p.  
St u d y D esi g n  
D o u bl e -bli n d, r a n d o miz e d , cr oss ov er tri al 
N u m b er of Sit es  
1 
E n d p oi nt  
T h e pri m ary e n d p oi nt is t h e l o w-bl o o d gl uc os e i n d ex 
(L B GI) i n t h e f o ur h o urs f oll o wi n g di n n er as m e as ur e d 
by  C G M , w h e n  usi n g  t h e  hy bri d  cl os e d -l o o p  ( H CL) 
s yst e m wit h  t h e  SI -i nf or m e d s m art  b ol us  c alc ul at or  
c o m p ar e d t o t h e st a n d ar d H CL s yst e m  al o n e .  
P o p ul ati o n  
K e y I ncl usi o n Crit eri a  
•  A g e 1 2  - <1 8  y e ars  
•  Cli nic al di a g n osis of T 1 D  
•  H o m e us e of a n i nsuli n p u m p a n d C G M f or at l e ast 3 
m o nt hs pri or t o st u dy e nr oll m e nt  
K e y Excl usi o n Crit eri a  
•  Hist ory of D K A i n t h e p ast 6 m o nt hs  
•  Hist ory  of  hy p o gl yc e mic  s eiz ur e  or  l oss  of  
c o nsci o us n ess i n t h e p ast 6 m o nt hs  
S a m pl e Siz e   
•  Pil ot st u dy: u p t o 3  p artici p a nts   
•  M ai n  St u dy:  3 0  p artici p a nts  ( u p  t o  7 0  m a y  b e  
c o ns e nt e d) 
Tr e at m e nt Gr o u ps  
•  All p artici p a nt s will b e assi g n e d t o b ot h tr e at m e nt 
gr o u ps at diff eri n g p oi nts of t h e st u dy (cr oss ov er)  
•  Gr o u p 1: st a n d ar d H CL  (U S S Vir gi ni a ) 
•  Gr o u p  2:  H CL (U S S  V ir gi ni a) wit h  s m art  b ol us 
c alc ul at or i nf or m e d by SI  

CLI NI C AL P R O T O C OL   
 
 
 
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 4  of 6 6  
 
P artici p a nt D ur ati o n  
Pil ot st u dy : U p t o 2 4 h o urs; M ai n st u dy: 6 d a ys or t w o 
4- d a y c a m p a d missi o ns  
Pr ot oc ol O v er vi e w/ S y n o psis  
Aft er  c o ns e nt  is  si g n e d,  eli gi bilit y  will  b e  ass ess e d.  
Eli gi bl e p artici p a nts will b e scr e e n e d, a n d d at a will b e 
c oll ect e d fr o m t h eir h o m e p u m p a n d C G M fr o m t h e 
pr ec e di n g  f o ur w e e ks . P artici p a nts  will  t h e n  b e  
r a n d o miz e d 1: 1 t o t h e us e of t h e st a n d ar d H CL s yst e m 
(U S S Vir gi ni a ) vs. t h e H CL s yst e m wit h a s m a rt b ol us 
c alc ul at or at  t h e  c a m p  a d missi o n . P artici p a nt s will 
cr oss ov er  i nt o  t h e  ot h er  gr o u p mi d w e e k O R  at  t h e  
s ec o n d c a m p  a d missi o n.  P artici p a nts  a n d  st u dy  
p ers o n n el acti v el y i nv ol v e d i n t h e st u dy will b e bli n d e d 
t o t h e tr e at m e nt gr o u ps.  
5 0  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 5  of 6 6  
 
T a bl e 1 . Sc h e d ul e of St u d y Visits a n d Pr oc e d ur e 
5 1  
  
5 2  
 
Scr e e ni n g  
D at a C oll ecti o n  
Pr e -A d missi o n 
C h ec k -i n 
St u d y 
A d missi o n(s) s 
P ost St u d y 
C h ec k -i n 
L oc ati o n 
Cli nic/ R e m ot e  
R e m ot e  
( 4 w e e ks 
hist oric al d at a)  
P h o n e/ E m ail  
C a m p H oli d a y 
Tr ails  
P h o n e/ E m ail  
I nf or m e d C o ns e nt 
X 
 
 
 
 
Eli gi bility Ass ess m e nt  
X 
 
 
 
 
M e dic al Hist ory  
X 
 
 
 
 
H b A 1c ( P O C)  
 
 
 
X ( a d missi o n # 1 
o nl y)  
 
Pr e g n a ncy t est (if a p plic a bl e)  
X 
 
 
X 
 
P hysic al Ex a m  
 
 
 
X 
 
Vit al Si g ns ( h ei g ht/ w ei g ht)  
 
 
 
X 
 
R a n d o miz ati o n  
 
 
 
X 
 
C O VI D -1 9  t esti n g 
 
 
X 
 
 
W e ar St u dy C G M a n d I ns uli n P u m p  
 
 
 
X 
 
R e vi e w di a b et es m a n a g e m e nt a n d A Es  
X 
X 
 
X 
X 
C h ec k -I n 
 
 
X 
 
X 

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 6  of 6 6  
 
T a bl e of C o nt e nts  
5 3  
C h a pt er 1:  B ac k gr o u n d  ......................................................................................................... 2 0  
5 4  
1. 1 I ntr o d ucti o n ........................................................................................................................ 2 0  
5 5  
1. 2 St u d y O bj ecti v e  ................................................................................................................... 2 1  
5 6  
1. 3 St u d y D esi g n ........................................................................................................................ 2 1  
5 7  
1. 4 P ur p os e/ O bj ecti v es of Cli nic al St u d y  .................................................................................. 2 2  
5 8  
1. 5 Pri m ar y S p ecific Ai m  ........................................................................................................... 2 2  
5 9  
1. 6 S ec o n d ar y S p ecific Ai m  ....................................................................................................... 2 2  
6 0  
C h a pt er 2:  St u d y D e vic es  ...................................................................................................... 2 3  
6 1  
2. 1 I ns uli n P u m p  ....................................................................................................................... 2 3  
6 2  
2. 2 C o nti n u o us  Gl uc os e M o nit or  .............................................................................................. 2 3  
6 3  
2. 3 Bl o o d Gl uc os e M et er a n d Stri ps  ......................................................................................... 2 3  
6 4  
2. 4 K et o n e M et er a n d Stri ps  ..................................................................................................... 2 3  
6 5  
2. 5 St u d y D e vic es Acc o u nt a bilit y Pr oc e d ur es  ........................................................................... 2 3  
6 6  
C h a pt er 3:  St u d y Scr e e ni n g  ................................................................................................... 2 4  
6 7  
3. 1 P artici p a nt R ecr uit m e nt a n d E nr oll m e nt  ............................................................................ 2 4  
6 8  
3. 2 I nf or m e d C o ns e nt a n d A ut h oriz ati o n Pr oc e d ur es  .............................................................. 2 4  
6 9  
3. 3 Scr e e ni n g Pr oc e d ur es  ......................................................................................................... 2 4  
7 0  
3. 4 P a rtici p a nt I ncl usi o n Crit eri a............................................................................................... 2 4  
7 1  
3. 5 P artici p a nt Excl usi o n Crit eri a  .............................................................................................. 2 5  
7 2  
3. 6 Eli gi bilit y Scr e e ni n g Pr oc e d ur es  .......................................................................................... 2 6  
7 3  
C h a pt er 4:  R a n d o miz ati o n Visit  ............................................................................................. 2 9  
7 4  
4. 1 Pil ot P artici p a nts  ................................................................................................................. 2 9  
7 5  
4. 2 M ai n St u d y P artici p a nts  ...................................................................................................... 2 9  
7 6  
C h a pt er 5:  St u d y E q ui p m e nt Tr ai ni n g  .................................................................................... 3 0  
7 7  
5. 1 C G M Tr ai ni n g  ...................................................................................................................... 3 0  
7 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 7  of 6 6  
 
5. 2 St u d y I ns uli n P u m p  ............................................................................................................. 3 0  
7 9  
C h a pt er 6:  Pil ot St u d y  ........................................................................................................... 3 2  
8 0  
6. 1 Q u alific ati o ns a n d R ol e of t h e St aff  .................................................................................... 3 2  
8 1  
6. 2 Pr e -A d missi o n C h eck -I n Visit .............................................................................................. 3 2  
8 2  
6. 3 A d missi o n C h eck -I n ............................................................................................................. 3 2  
8 3  
6. 4 St u d y M e als  ......................................................................................................................... 3 3  
8 4  
6. 5 M e al R e q uir e m e nts ............................................................................................................. 3 3  
8 5  
6. 6 A d missi o n Acti viti es  ............................................................................................................ 3 3  
8 6  
6. 7 A d missi o n Disc h ar g e  ........................................................................................................... 3 4  
8 7  
6. 8 P ost A d missi o n C h eck -I n Visit ............................................................................................. 3 4  
8 8  
C h a pt er 7:  M e dic al M o nit or  .................................................................................................. 3 5  
8 9  
7. 1 St u d y S af et y D at a R e vi e w  ................................................................................................... 3 5  
9 0  
7. 2 M e dic al M o nit or D ecisi o ns  ................................................................................................. 3 5  
9 1  
7. 3 M e dic al M o nit or M ai n St u d y S af ety D at a R e vi e w  .............................................................. 3 5  
9 2  
C h a pt er 8:  M ai n St u d y  .......................................................................................................... 3 6  
9 3  
8. 1 Q u alific ati o ns a n d R ol e of t h e St aff  .................................................................................... 3 6  
9 4  
8. 2 Pr e -A d missi o n(s) C h eck -i n Visit .......................................................................................... 3 6  
9 5  
8. 3 A d missi o n(s) C h eck -i n Pr oc e d ur es ...................................................................................... 3 6  
9 6  
8. 4 M ai n A d missi o n(s) Acti viti es a n d Pr oc e d ur es  .................................................................... 3 7  
9 7  
8. 5 A d missi o n(s) Disc h ar g e  ....................................................................................................... 4 0  
9 8  
8. 6 P ost A d missi o n(s) C h eck -I n Visit ......................................................................................... 4 0  
9 9  
8. 7 St u d y S yst e m Iss u es  ............................................................................................................ 4 0  
1 0 0  
C h a pt er 9:  T esti n g Pr oc e d ur es  .............................................................................................. 4 2  
1 0 1  
9. 1 L a b or at or y / P oi nt of C ar e T esti n g  ...................................................................................... 4 2  
1 0 2  
C h a pt er 1 0:  Ris ks Ass oci at e d wit h Cli nic al Tri al  ..................................................................... 4 3  
1 0 3  
1 0. 1 P ot e nti al Ris ks a n d B e n efits of t h e I nv esti g ati o n al D e vic e  ............................................... 4 3  
1 0 4  
1 0. 2 G e n er al C o nsi d er ati o ns ..................................................................................................... 4 6  
1 0 5  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 8  of 6 6  
 
1 0. 3 C O VI D -1 9 Ris k Miti g ati o n Pl a n a n d J ustific ati o n  .............................................................. 4 7  
1 0 6  
C h a pt er 1 1:  A d v ers e E v e nts, D e vic e Iss u es, a n d St o p pi n g R ul es  ............................................ 5 0  
1 0 7  
1 1. 1 D efi niti o ns  ......................................................................................................................... 5 0  
1 0 8  
1 1. 2 R e p ort a bl e Ev e nts  ............................................................................................................. 5 1  
1 0 9  
1 1. 3 R el ati o ns hi p of A d v ers e Ev e nt t o St u d y D e vic e  ................................................................ 5 2  
1 1 0  
1 1. 4 C O VI D -1 9 Tr a ns missi o n / S y m pt o ms  ................................................................................ 5 3  
1 1 1  
1 1. 5 I nt e nsit y of A d v ers e Ev e nt  ................................................................................................ 5 4  
1 1 2  
1 1. 6 C o di n g of A d v ers e Ev e nts  ................................................................................................. 5 4  
1 1 3  
1 1. 7 O utc o m e of A d v ers e Ev e nts .............................................................................................. 5 4  
1 1 4  
1 1. 8 R e p ort a bl e D e vic e Iss u es  .................................................................................................. 5 5  
1 1 5  
1 1. 9 Ti mi n g of Ev e nt R e p orti n g  ................................................................................................ 5 6  
1 1 6  
1 1. 1 0 St o p pi n g Crit eri a  ............................................................................................................. 5 6  
1 1 7  
1 1. 1 1 I n d e p e n d e nt S af et y O v ersi g ht  ........................................................................................ 5 7  
1 1 8  
1 1. 1 2 D efi niti o n of a D at a Br e ac h  ............................................................................................. 5 7  
1 1 9  
C h a pt er 1 2:  Misc ell a n e o us C o nsi d er ati o ns  ............................................................................ 5 8  
1 2 0  
1 2. 1 Pr o hi bit e d M e dic ati o ns, Tr e at m e nts, a n d Pr oc e d ur es ..................................................... 5 8  
1 2 1  
1 2. 2 P artici p a nt Wit h dr a w al  ..................................................................................................... 5 8  
1 2 2  
1 2. 3 C o nfi d e nti alit y  ................................................................................................................... 5 8  
1 2 3  
C h a pt er 1 3 : St atistic al C o nsi d er ati o n  .................................................................................... 5 9  
1 2 4  
1 3. 1 D esi g n a n d R a n d o miz ati o n  ............................................................................................... 5 9  
1 2 5  
1 3 . 2 S a m pl e Siz e ....................................................................................................................... 5 9  
1 2 6  
1 3. 3 O utc o m e M e as ur es  ........................................................................................................... 5 9  
1 2 7  
1 3. 4 S af et y A n al ys es  ................................................................................................................. 6 0  
1 2 8  
1 3. 5 B as eli n e D escri pti v e St atistics ........................................................................................... 6 0  
1 2 9  
1 3. 6 D e vic e Iss u es  ..................................................................................................................... 6 0  
1 3 0  
C h a pt er 1 4:  D at a C oll ecti o n a n d M o nit ori n g  ......................................................................... 6 2  
1 3 1  
1 4. 1 C as e R e p ort F or ms a n d D e vic e D at a  ................................................................................. 6 2  
1 3 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 1 9  of 6 6  
 
1 4. 2 St u d y R ec or ds R et e nti o n  .................................................................................................. 6 2  
1 3 3  
1 4. 3 Pr ot oc ol D e vi ati o ns  ........................................................................................................... 6 2  
1 3 4  
C h a pt er 1 5:  Et hics/ Pr ot ecti o n of H u m a n P artici p a nts  ........................................................... 6 3  
1 3 5  
1 5. 1 Et hics St a n d ar d  ................................................................................................................. 6 3  
1 3 6  
1 5. 2 I nstit uti o n al R e vi e w B o ar ds  .............................................................................................. 6 3  
1 3 7  
1 5. 3 I nf or m e d C o ns e nt Pr oc ess  ................................................................................................ 6 3  
1 3 8  
C h a pt er 1 6:  R ef er e nc es  ......................................................................................................... 6 5  
1 3 9  
 
1 4 0  
 
 
1 4 1  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 0  of 6 6  
 
C h a pt er 1:  B ac k gr o u n d  
1 4 2  
 
1 4 3  
T h e m a n a g e m e nt of t y p e 1 di a b et es ( T 1 D) i n v ol v es cl os e m o nit ori n g of bl o o d gl uc os e ( B G) l e v els 
1 4 4  
al o n g wit h fr e q u e nt a d mi nistr ati o n of s u bc ut a n e o us i ns uli n, eit h er wit h  m ulti pl e d ail y i nj ecti o ns 
1 4 5  
or vi a c o nti n u o us i nf usi o n fr o m a n i ns uli n p u m p  ( 1). T h e a m o u nt of i ns uli n gi v e n t o c o v er a m e al 
1 4 6  
is d e p e n d e nt u p o n s e v er al f act ors i ncl u di n g t h e a m o u nt of c ar b o h y dr at es c o ns u m e d, t h e pr e -
1 4 7  
m e al B G  l e v el, t h e l e n gt h of ti m e si nc e t h e l ast i ns uli n a d mi nistr ati o n, a n d h o w r es p o nsi v e or 
1 4 8  
s e nsiti v e t h e p ers o n is to i ns uli n (i. e. , h o w m uc h 1 u nit of i ns uli n is ex p ect e d t o dr o p his/ h er B G).  
1 4 9  
N ot a bl y, a p ers o n’s i ns uli n s e nsiti vit y (SI ) is n ot c o nst a nt, fl uct u ati n g t hr o u g h o ut t h e d a y b as e d 
1 5 0  
o n h or m o n es a n d ot h er f act ors  s uc h as p h ysic al acti vity  ( 2-6) . T h es e fl uct u ati o ns i n SI m a k e  
1 5 1  
d et er mi ni n g t h e a p pr o pri at e i ns uli n d osi n g at a n y gi v e n ti m e q uit e c h all e n gi n g , p artic ul arl y f or 
1 5 2  
m e als f oll o wi n g ex ercis e. D es pit e t h e a v ail a bil ity of g ui d eli n es f or m a n a gi n g ex ercis e wit h T 1 D 
1 5 3  
( 7), m a n y a d ol esc e nts wit h T 1 D  r e p ort n ot m a ki n g t h e a p pr o pri at e  i ns uli n a dj ust m e nts ar o u n d  
1 5 4  
ex ercis e ( 8). W hil e  t h e us e of c o nti n u o us gl uc os e m o nit ori n g ( C G M) d e vic es a n d hy bri d cl os e d 
1 5 5  
l o o p ( H CL) “ artifici al p a ncr e as” s yst e ms h a v e b e e n s h o w n t o si g nific a ntl y i m pr o v e gl yc e mic 
1 5 6  
c o ntr ol o v er all i n p e o pl e wit h T 1 D ( 9-1 1) , d a yti m e c o ntr ol r e m ai ns s u b o pti m al, l ar g el y d u e t o t h e 
1 5 7  
c h all e n g es  s urr o u n di n g m e als  a n d ex ercis e . Acc or di n gl y,   sm art b ol us  c alc ul at ors  ar e u n d er  
1 5 8  
d e v el o p m e nt  t o t a k e i nt o acc o u nt c h a n gi n g m et a b olic  n e e ds  a n d f urt h er i m pr o v e gl yc e mic 
1 5 9  
c o ntr ol ( 1 2, 1 3).  
1 6 0  
T h e pr o p os e d SI -i nf or m e d b ol us c alcul at or w as d esi g n e d t o a dj ust t h e i ns uli n d osi n g f or c h a n g es 
1 6 1  
i n SI at t h e ti m e t h e b ol us is d eli v er e d. If t h e r e al-ti m e SI is esti m at e d t o b e t h e s a m e as t h e 
1 6 2  
p ers o n’s t y pic al SI at t h at ti m e, t h e a d mi nist er e d b ol us will r e m ai n u nc h a n g e d. H o w e v er, it will 
1 6 3  
b e i ncr e as e d/ d ecr e as e d if t h e p artici p a nt  is l ess/ m or e s e nsiti v e t h a n us u al at t h e ti m e t h e b ol us 
1 6 4  
is a d mi nist er e d. Of n ot e, th e r ati o us e d t o m o d ul at e t h e b ol us will b e s at ur at e d i n or d er  t o n ot 
1 6 5  
all o w f or m o dific ati o ns l ar g er t h a n 3 0 % of t h e ori gi n al b ol us a m o u nt ( i. e., t h e d os e s u g g est e d will 
1 6 6  
b e b et w e e n 7 0 % a n d 1 3 0 % of t h e st a n d ar d d os e i n dic at e d b y t h e b ol us c alc ul at or i m pl e m e nt e d 
1 6 7  
i n t h e Di As s yst e m usi n g t h e p artici p a nt’s pr o gr a m m e d i ns uli n p ar a m et ers).  
1 6 8  
T h e SI -i nf or m e d s m art b ol us c alc ul at or w as first t est e d i n silic o usi n g t h e U ni v ersity of Vir gi ni a 
1 6 9  
( U V A)/ P a d o v a Ty p e 1 Di a b et es Si m ul at or, a si m ul ati o n pl atf or m a p pr o v e d b y t h e F D A as  a 
1 7 0  
s u bstit ut e t o pr ecli nic al tri als i n t esti n g i ns uli n-d osi n g  al g orit h ms  ( 1 4), a n d a v ersi o n h as b e e n 
1 7 1  
s ucc essf ull y us e d i n a d ecisi o n s u p p ort syst e m f o u n d t o d ecr e as e gl uc os e v ari a bility ( 1 5). T h e 
1 7 2  
s m art b ol us c alc ul at or w as s u bs e q u e ntl y s h o w n t o b e f e asi bl e a n d eff ecti v e i n a s m all cli nic al tri al 
1 7 3  
of 1 5 a d ults wit h T 1 D, d ecr e asi n g  p ost pr a n di al h y p o gl yc e mi a f oll o wi n g o n e c o ntr oll e d m e al aft er 
1 7 4  
a st a n d ar diz e d ex ercis e p eri o d ( 1 6).  
1 7 5  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 1  of 6 6  
 
I n t his st u d y, w e pr o p os e i nt e gr ati n g t h e SI -i nf or m e d s m art b ol us c alc ul at or i nt o a m o bil e 
1 7 6  
pl atf or m ( t h e Di As, or Di a b et es Assist a nt) r u n ni n g t h e U V A l e g acy H CL c o ntr ol al g orit h m ( U SS 
1 7 7  
Vir gi ni a – w hic h l e d t o t h e F D A -a p pr o v e d C o ntr ol -I Q H CL s yst e m), f or ext e n d e d us e i n a d ol esc e nts 
1 7 8  
wit h T 1 D  i n sit u ati o ns of i ncr e as e d p h ysic al acti vity a n d ex ercis e . 
1 7 9  
 
1 8 0  
T h e p ur p os e of t his st u d y is t o t est t h e SI -i nf or m e d s m art b ol us c alc ul at or  w h e n us e d r e p e at e dl y 
1 8 1  
f or all b ol us i ns uli n d osi n g o v er t h e c o urs e of s e v er al d a ys, i n a d ol esc e nts wit h T 1 D usi n g a H CL 
1 8 2  
s yst e m a n d e n g a gi n g i n pr ol o n g e d p h ysic al acti vity . T h e ex p ect e d fl uct u ati o ns i n SI d u e t o t h e 
1 8 3  
i ncr e as e d p h ysic al acti vit y will a p pr o pri at el y c h all e n g e t h e s yst e m . 
1 8 4  
 
1 8 5  
T his is a si n gl e c e nt er, d o u bl e-bli n d, r a n d o miz e d, cr oss o v er tri al. T h e tri al will b e h el d  at a l oc al 
1 8 6  
c a m p f acility a n d will c o nsist of EI T H E R a w e e kl o n g ( 6 d a y/ 5 ni g ht) c a m p O R  t w o l o n g w e e k e n ds 
1 8 7  
(4 d a y/ 3 ni g ht) s e p ar at e d b y a w as h o ut p eri o d of a b o ut o n e w e e k.  
1 8 8  
T h e st u d y will d e pl o y a c o ntr ol a n d a n ex p eri m e nt al s yst e m i n r a n d o m or d er.  I n t h e cas e of a 
1 8 9  
w e e kl o n g c a m p, p artici p a nts will b e r a n d o m l y assi g n e d t h e first s yst e m t o us e a n d will cr oss o v er 
1 9 0  
t o t h e ot h er s yst e m mi d w e e k; i n t h e c as e of t w o l o n g w e e k e n ds, p artici p a nts will b e r a n d o m l y 
1 9 1  
assi g n e d t h e s yst e m t o us e o v er t h e first w e e k e n d a n d will cr oss o v er t o t h e ot h er syst e m d uri n g 
1 9 2  
t h e s ec o n d w e e k e n d. W e will t ar g et e nr oll m e nt of 3 0 a d ol esc e nts ( a g e 1 2 - <1 8 y e ars) wit h T 1 D 
1 9 3  
w h o c urr e ntl y m a n a g e t h eir di a b et es wit h a n i ns uli n p u m p a n d a C G M s yst e m.  
1 9 4  
P artici p a nt s will u n d er g o a n i niti al Scr e e ni n g Visit aft er w hic h d at a fr o m t h eir p ers o n al i ns uli n 
1 9 5  
p u m p a n d C G M fr o m t h e pr e vi o us f o ur w e e ks will b e d o w nl o a d e d. T his r etr os p ecti v e d at a 
1 9 6  
c oll ecti o n p eri o d m a y b e ext e n d e d t o g at h er m or e d a ys of q u ality d at a if n e e d e d p er t h e pri nci p al 
1 9 7  
i n v esti g at or’s j u d gm e nt. T his d at a will t h e n b e us e d t o d et er mi n e e ac h p artici p a nt ’s ty pic al d ail y 
1 9 8  
fl uct u ati o ns i n SI .  
1 9 9  
Aft er  c o m pl eti o n of t h e Scr e e ni n g Visit, if p artici p a nts ar e eli gi bl e t o t a k e p art i n t h e st u d y, t h ey 
2 0 0  
will u n d er g o a R a n d o miz ati o n Visit. P artici p a nts will b e r a n d o miz e d 1: 1 t o t w o gr o u ps, eit h er 
2 0 1  
usi n g  US S Vir gi ni a  (c o ntr ol s yst e m) or U SS Vir gi ni a wit h t h e SI -i nf or m e d s m art b ol us c alc ul at or 
2 0 2  
( ex p eri m e nt al s yst e m) first, a n d will cr oss o v er i nt o t h e ot h er tr e at m e nt ar m  d uri n g t h e st u d y. 
2 0 3  
P artici p a nts a n d st u d y p ers o n n el acti v el y i n v ol v e d i n t h e c a m p will b e bli n d e d t o t h e assi g n m e nt  
2 0 4  
of st u d y p artici p a nts t o tr e at m e nt gr o u ps. 
2 0 5  
U p o n c o m pl eti o n of all visits l e a di n g u p t o c a m p visit (s), p artici p a nt s will pr es e nt f or st u d y 
2 0 6  
a d missi o n(s)  at C a m p H oli d a y Tr ails   – a c a m p f or c hil dr e n wit h c hr o nic m e dic al c o n diti o ns, i n 
2 0 7  
C h arl ott es vill e, V A . A t t h e ti m e of t h e a d missi o n(s) , a P O C H b A 1c will b e o bt ai n e d, a n d a p h ysic al 
2 0 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 2  of 6 6  
 
ex a m will b e p erf or m e d . D uri n g t h e e ntir ety of c a m p a d missi o n(s)  d ur ati o n, p artici p a nt s will e at 
2 0 9  
all m e als at c a m p a n d p artici p at e i n d ail y acti viti es  i ncl u di n g hi ki n g, a er o bics , art, etc. Me als a n d 
2 1 0  
acti viti es will b e k e pt si mil ar d uri n g t h e us e of t h e t w o s yst e ms  (c o ntr ol a n d ex p eri m e nt al), i n 
2 1 1  
or d er n ot t o bi as st u d y o utc o m es . 
2 1 2  
Fi g ur e 1  b el o w  pr es e nts a n o v er vi e w of t h e ti m eli n e of t h e m ai n st u d y visits , i n t h e c as e of t w o 
2 1 3  
l o n g w e e k e nds . 
2 1 4  
 
2 1 5  
Fi g ur e 1 :  St u d y Di a gr a m 
2 1 6  
 
2 1 7  
 St u d y P artici p a nts  
2 1 8  
E nr oll m e nt i n t h e st u d y will pr oc e e d wit h t h e g o al of c o m pl eti n g a p pr oxi m at el y 3 0 p artici p a nt s. 
2 1 9  
U p t o 7 0  p artici p a nts m a y si g n t h e c o ns e nt f or m.  
2 2 0  
 Cli nic al Sit es  
2 2 1  
T h e st u d y will b e p erf or m e d at t h e U ni v ersity of Vir gi ni a.  
2 2 2  
 
2 2 3  
•  D e m o nstr at e t h e s af et y a n d f e asi bility of usi n g t h e S I-i nf or m e d s m art b ol us c alc ul at or 
2 2 4  
i n a n H CL s yst e m, o v er a n ext e n d e d p eri o d of ti m e wit h m ulti pl e m e als.  
2 2 5  
 
2 2 6  
•  D e m o nstr at e t h at t h e us e of t h e SI -i nf or m e d s m art b ol us c alc ul at or i n a n H CL s yst e m 
2 2 7  
pr o vi d es i ncr e as e d pr ot ecti o n a g ai nst h y p o gl yc e mi a.  
 
2 2 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 3  of 6 6  
 
C h a pt er 2:  St u d y D e vic es  
2 2 9  
 
2 3 0  
T h e st u d y s yst e m will i n cl u d e t h e T a n d e m t: a p r es e arc h p u m p c o n n ect e d t o t h e U V A Di As s yst e m 
2 3 1  
r u n ni n g o n a d e dic at e d ext er n al s m art p h o n e, i m pl e m e nti n g eit h er t h e US S Vir gi ni a  al g orit h m 
2 3 2  
al o n e or t h e US S Vir gi ni a  al g orit h m wit h t h e s m art b ol us c alc ul at or .  
2 3 3  
 
2 3 4  
T h e st u d y C G M will i ncl u d e D exc o m G 6 tr a ns mitt er a n d s e ns ors.  T h e C G M s e ns or is vi a bl e f or 1 0 
2 3 5  
d a ys.  Li k e t h e i ns uli n p u m p, th e C G M s yst e m will b e c o n n ect e d t o Di As.  
2 3 6  
 
2 3 7  
U p o n  n e e d,  bl o o d  gl uc os e  l e v els  will  b e  m e as ur e d  usi n g  t h e  st u d y bl o o d  gl uc os e  m et er  
2 3 8  
( gl uc o m et er). T h e C G M d e vic e will b e c ali br a t e d, if n e e d e d, usi n g t h e st u d y gl uc o m et er a n d stri ps 
2 3 9  
i n acc or d a nc e wit h t h e m a n uf act ur er’s l a b eli n g. Gl uc o m et ers will b e a v ail a bl e d uri n g t h e st u d y 
2 4 0  
a d missi o n(s) .  
2 4 1  
 
2 4 2  
U p o n n e e d, bl o o d k et o n e l e v els will b e m e as ur e d usi n g t h e A b b ott Pr ecisi o n Xtr a m et ers a n d 
2 4 3  
stri ps i n acc or d a nc e wit h t h e m a n uf act ur er’s l a b eli n g. T h e bl o o d gl uc os e m et er c o m p o n e nt of 
2 4 4  
t h e Pr ecisi o n Xtr a D e vic e will n ot b e us e d. K et o n e m et ers will b e a v ail a bl e d uri n g t h e st u d y 
2 4 5  
a d missi o n(s) . 
2 4 6  
 
2 4 7  
D e vic e s eri al n u m b ers will b e r ec or d e d, a n d us e of e q ui p m e nt will b e tr ack e d.  
 
2 4 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 4  of 6 6  
 
C h a pt er 3:  St u d y Scr e e ni n g   
2 4 9  
 
2 5 0  
P artici p a nts will b e r ecr uit e d fr o m t h e U V A C e nt er f or Di a b et es T ec h n ol o gy r e gistr y, s oci al m e di a 
2 5 1  
a d v ertis e m e nts, p h ysici a n c o nt acts at p e di atric di a b et es cli nics i n Vir gi ni a, a n d pr e vi o us c a m p 
2 5 2  
att e n d a nc e  d at a.  T h e  e nr oll m e nt  g o al  i n  t h e  pil ot  st u d y  will  b e  t o  c o m pl et e  u p  t o  t hr e e 
2 5 3  
p artici p a nt s. U p t o f o ur p artici p a nts m a y si g n c o ns e nt/ ass e nt f or ms. T h e e nr oll m e nt g o al f or t h e 
2 5 4  
m ai n st u d y is t o c o m pl et e 3 0 p artici p a nts. U p t o 7 0  p artici p a nts m a y si g n t h e c o ns e nt f or m.  
2 5 5  
 
2 5 6  
B ef or e  c o ns e nt  h as  b e e n  o bt ai n e d,  p arti ci p a nts  will  b e  as k e d  i ncl usi o n/excl usi o n  crit eri a  
2 5 7  
q u esti o ns d uri n g pr escr e e ni n g t o d et er mi n e st u d y eli gi bility. B ef or e c o m pl eti n g a ny pr oc e d ur es 
2 5 8  
or c oll ecti n g a n y d at a t h at ar e n ot p art of us u al c ar e, writt e n i nf or m e d c o ns e nt will b e o bt ai n e d . 
2 5 9  
I nf or m e d c ons e nt will b e o bt ai n e d fr o m a p ar e nt f or p artici p a nts < 1 8 y e ars ol d a n d ass e nt will 
2 6 0  
als o b e o bt ai n e d fr o m p artici p a nts w h o ar e < 1 8 y e ars ol d. P ot e nti al eli gi bility m a y b e ass ess e d as 
2 6 1  
p art of a r o uti n e -c ar e ex a mi n ati o n.  
2 6 2  
A p artici p a nt is c o nsi d er e d e nr oll e d  w h e n t h e i nf or m e d c o ns e nt f or m h as b e e n si g n e d  b y t h e 
2 6 3  
p artici p a nt a n d t h e st u d y t e a m . 
2 6 4  
C o ns e nti n g pr oc e d ur es a n d d oc u m e nt ati o n is d efi n e d i n s ecti o n 1 5. 3 .  
2 6 5  
 
2 6 6  
Aft er i nf or m e d c o ns e nt h as b e e n si g n e d, a p ot e nti al p artici p a nt will b e e v al u at e d f or st u d y 
2 6 7  
eli gi bilit y t hr o u g h t h e elicit ati o n of a m e dic al hist or y , p erf or m a nc e of a ph ysic al ex a mi n ati o n b y 
2 6 8  
lic e ns e d p ers o n n el, a n d pr e g n a ncy t esti n g (if a p plic a bl e) t o scr e e n f or excl usi o n ar y m e dic al 
2 6 9  
c o n diti o ns. A p h ysic al ex a m d oc u m e nt e d i n t h e pri or y e ar c a n s uffic e. T h e scr e e ni n g visit c a n b e 
2 7 0  
p erf or m e d i n c li nic or b y vi d e o c o nf er e nci ng.  
2 7 1  
 
2 7 2  
T h e p artici p a nts m ust m e et t h e f oll o wi n g i ncl usi o n crit eri a i n or d er t o b e eli gi bl e t o p artici p at e i n 
2 7 3  
t h e st u d y: 
2 7 4  
1.  A g e ≥1 2 a n d < 1 8  y e ars ol d  at ti m e of c o ns e nt  
2 7 5  
2.  Cli nic al di a g n osis, b as e d o n i n v esti g at or ass ess m e nt, of T 1 D  f or at l e ast o n e y e ar  
2 7 6  
3.  C urr e ntl y usi n g i ns uli n f or at l e ast six m o nt hs  
2 7 7  
4.  C urr e ntl y usi n g a n i ns uli n p u m p f or at l e ast t hr e e m o nt hs  
2 7 8  
5.  C urr e ntl y usi n g a C G M s yst e m f or at l e ast t hr e e m o nt hs  
2 7 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 5  of 6 6  
 
6.  H a vi n g at l e ast 7 5 % of C G M d at a  o v er t h e pr e vi o us f o ur w e e ks  
2 8 0  
7.  Usi n g i ns uli n p ar a m et ers s uc h as c ar b o hy dr at e r ati o a n d c orr ecti o n f act ors c o nsist e ntl y 
2 8 1  
o n t h eir p u m p i n or d er t o d os e i ns uli n f or m e als or c orr ecti o ns  
2 8 2  
8.  Acc ess t o i nt er n et a n d willi n g n ess t o u pl o a d d at a d uri n g t h e st u d y as n e e d e d  
2 8 3  
9.  F or f e m al es, n ot c urr e ntl y k n o w n t o b e pr e g n a nt  or br e astf e e di n g  
2 8 4  
1 0.  A n e g ati v e uri n e pr e g n a ncy t est will b e r e q uir e d f or all f e m al es of c hil d b e ari n g p ot e nti al  
2 8 5  
1 1.  Willi n g n ess t o s us p e n d us e of a n y p ers o n al C G M f or t h e d ur ati o n of t h e cli nic al tri al o nc e 
2 8 6  
t h e st u d y C G M is i n us e 
2 8 7  
1 2.  Willi n g n ess t o s witc h t o lis pr o ( H u m al o g) or as p art ( N o v ol o g) if n ot usi n g alr e a d y, a n d t o 
2 8 8  
us e n o ot h er i ns uli n b esi d es lis pr o ( H u m al o g) or as p art ( N o v ol o g) d uri n g t h e st u d y  
2 8 9  
1 3.  T ot al d ail y i ns uli n d os e ( T D D) of at l e ast 1 0 U/ d a y  
2 9 0  
1 4.  Willi n g n e ss n ot t o st art a n y n o n-i ns uli n gl uc os e-l o w eri n g a g e nt d uri n g t h e c o urs e of t h e 
2 9 1  
tri al  (i ncl u di n g  m etf or mi n,  GL P-1  a g o nists,  pr a mli nti d e,  D P P -4  i n hi bit ors,  S GL T - 2 
2 9 2  
i n hi bit ors, bi g u a ni d es, s ulf o n yl ur e as a n d n at ur ac e utic als)  
2 9 3  
1 5.  Willi n g n ess t o e at at l e ast 4 0 gr a m s of c ar b o h y dr at es p er m e al 
2 9 4  
1 6.  A n u n d erst a n di n g a n d willi n g n ess t o f oll o w t h e pr ot oc ol a n d si g n e d i nf or m e d c o ns e nt  
2 9 5  
1 7.  P artici p a nts a n d p ar e nt/l e g al g u ar di a ns will b e pr of ici e nt i n r e a di n g a n d writi n g i n E n glis h 
2 9 6  
1 8.  Willi n g n ess t o c o m pl y wit h C O V I D-1 9 pr ec a uti o ns as d efi n e d b y t h e st u d y t e a m ( st u d y 
2 9 7  
t e a m will r ef er e nc e s ecti o n 1 0. 3 )  
2 9 8  
1 9.  H a vi n g c o m pl et e d a C O VI D -1 9 v a cci n ati o n wit h a n F D A-a p pr o v e d C O VI D -1 9 v acci n e at 
2 9 9  
l e ast t w o w e e ks b ef or e t h e first st u d y a d missi o n a n d willi n g t o pr o vi d e a c o p y of t h e 
3 0 0  
C O VI D -1 9 v acci n ati o n c ar d  
3 0 1  
 
3 0 2  
T h e p artici p a nt m ust n ot h a v e a n y of t h e f oll o wi n g excl usi o n crit eri a i n or d er t o b e eli gi bl e t o 
3 0 3  
p artici p at e i n t h e st u d y :  
3 0 4  
1.  H e m o gl o bi n A 1c  < 6% or  >1 0 % if m e as ur e d at scr e e ni n g or a v ail a bl e fr o m hist oric al m e dic al 
3 0 5  
r e p ort p erf or m e d wit hi n t h e l ast 6 m o nt hs; i n a bs e nc e of a v ali d H b A 1c m e as ur e m e nt, 
3 0 6  
a v er a g e bl o o d gl uc os e esti m at e d fr o m C G M d at a t o b e a p pr oxi m at el y b et w e e n 1 0 0 a n d 2 4 0 
3 0 7  
m g/ dL  
3 0 8  
2.  Hist or y of di a b e tic k et o aci d osis ( D K A) i n t h e 6 m o nt hs pri or t o e nr oll m e nt  
3 0 9  
3.  S e v er e h y p o gl yc e mi a r es ulti n g i n s eiz ur e or  l oss of c o nsci o us n ess i n t h e 6  m o nt hs pri or t o 
3 1 0  
e nr oll m e nt  
3 1 1  
4.  Pr e g n a ncy or i nt e nt t o b ec o m e pr e g n a nt d uri n g t h e tri al  
3 1 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 6  of 6 6  
 
5.  C urr e ntl y br e astf e e di n g or pl a n ni n g t o br e astf e e d  
3 1 3  
6.  C urr e ntl y b ei n g tr e at e d f or a s eiz ur e dis or d er  
3 1 4  
7.  Pl a n n e d s ur g er y d uri n g st u d y d ur ati o n  
3 1 5  
8.  Hist or y of c ar di ac arr h yt h mi a ( exc e pt f or b e ni g n pr e m at ur e atri al c o ntr acti o ns a n d b e ni g n 
3 1 6  
pr e m at ur e v e ntric ul ar c o ntr acti o ns w hic h ar e p er mitt e d)  
3 1 7  
9.  C urr e nt  tr e at m e nt  wit h  a n y  n o n -i ns uli n  gl uc os e-l o w eri n g  a g e nt  (m etf or mi n , GL P -1 
3 1 8  
a g o nists, pr a mli nti d e, D P P -4 i n hi bit ors, S GL T-2 i n hi bit ors, bi g u a ni d es, s ulf o n yl ur e as a n d 
3 1 9  
n at ur ac e utic als)   
3 2 0  
1 0.  A k n o w n m e dic al c o n diti o n t h at i n t h e j u d g m e nt of t h e i n v esti g at or mi g ht i nt erf er e wit h 
3 2 1  
t h e c o m pl eti o n of t h e pr ot oc ol s uc h as t h e f oll o wi n g ex a m pl es:  
3 2 2  
i. 
Si g nific a nt c hr o nic ki d n e y dis e as e ( e GF R < 6 0) or h e m o di al ysis   
3 2 3  
ii. 
Si g nific a nt li v er dis e as e   
3 2 4  
iii. 
Hist or y of a dr e n al i ns uffici e ncy   
3 2 5  
i v. 
Hist or y of a b n or m al T S H c o nsist e nt wit h h y p ot h yr oi dis m or h y p ert h yr oi dis m t h at 
3 2 6  
is n ot a p pr o pri at el y tr e at e d O R hist or y of t h yr oi d c a nc er   
3 2 7  
v.  
Us e of o n g oi n g or al or i nj ect a bl e st er oi ds i n t h e l ast 8  w e e ks   
3 2 8  
1 1.   Us e of a n i ns uli n d eli v er y m ec h a nis m t h at is n ot d o w nl o a d a bl e b y t h e p artici p a nt  or st u d y 
3 2 9  
t e a m 
3 3 0  
1 2.  K n o w n c o nt act wit h C O VI D -p ositi v e i n di vi d u al wit hi n 7 d a ys of a n y st u d y a d missi o n(s)  
3 3 1  
1 3.  S y m pt o ms of C O VI D -1 9 ( e. g., f e v er, s h ort n ess of br e at h, u n ex p ect e d l oss of t ast e or s m ell) 
3 3 2  
d e v el o p e d aft er t a ki n g t h e m a n d at or y C O VI D -1 9 P C R t est pri or t o  a n y st u d y a d missi o n(s)  
3 3 3  
or d uri n g st u d y a d missi o n(s) p artici p ati o n  
3 3 4  
1 4.  A p ositi v e C O VI D -1 9  t est wit hi n 1 0  d a ys of a n y st u d y a d missi o n(s)  
3 3 5  
1 5.  N ot b ei n g f ull y v acci n at e d at t h e ti m e of t h e first c a m p a d missi o n ( acc or di n g t o C D C 
3 3 6  
g ui d eli n es a p ers o n is i nt e n d e d t o b e f ull y v acci n at e d aft er t w o w e e ks fr o m eit h er t h e 
3 3 7  
s ec o n d d os e of t h e Pfiz er or M o d er n a v acci n e, or t h e si n gl e d os e of t h e J o h ns o n   & 
3 3 8  
J o h ns o n v acci n e)  
3 3 9  
 
3 4 0  
T h e  p artici p a nt will b e e v al u at e d f or st u dy i ncl usi o n a n d excl usi o n eli gi bility  aft er t h e i nf or m e d 
3 4 1  
c o ns e nt f or m h as b e e n si g n e d b y t h e p artici p a nt a n d t h e st u d y t e a m . I n di vi d u als w h o d o n ot 
3 4 2  
i niti all y m e et st u d y eli gi bilit y r e q uir e m e nts m a y b e r escr e e n e d at a l at er d at e p er i n v esti g at or 
3 4 3  
discr eti o n.  T h e f oll o wi n g i nf or m ati o n will b e c oll ect e d d uri n g t h e scr e e ni n g pr oc e d ur es : 
3 4 4  
•  D e m o gr a p hics  
3 4 5  
•  D at e o f b irt h 
3 4 6  
•  G e n d er  
3 4 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 7  of 6 6  
 
•  R ac e  
3 4 8  
•  Et h nicit y  
3 4 9  
•  M e dic al Hist or y  
3 5 0  
•  D ur ati o n of dis e as e ( n u m b er of y e ars)  
3 5 1  
•  Hist or y of i ns uli n p u m p us e a n d c urr e nt i ns uli n p u m p m o d el 
3 5 2  
•  Hist or y of C G M us e  
3 5 3  
•  C urr e nt tr e at m e nt  
3 5 4  
i. 
B as al r at es  
3 5 5  
ii. 
C ar b o h y dr at e r ati os  
3 5 6  
iii. 
I ns uli n s e nsiti vit y f act ors 
3 5 7  
i v. 
T ar g et gl uc os e  
3 5 8  
v.  
A v er a g e d ail y i ns uli n  
3 5 9  
•  Hist or y of di a b etic k et o aci d osis  
3 6 0  
•  Hist or y of s e v er e h y p o gl yc e mi a  
3 6 1  
•  Hist or y of s eiz ur es  
3 6 2  
•  L oss of c o nsci o us n ess 
3 6 3  
•  S ur gic al hist or y  
3 6 4  
•  All er gi es  
3 6 5  
•  C o nc o mit a nt m e dic ati o ns  
3 6 6  
•  P h ysic al  Ex a mi n ati o n  – A  hist oric al  hist or y  a n d  p h ysic al  r e p ort  wit hi n  5 2  w e eks  of  
3 6 7  
scr e e ni n g a p p oi nt m e nts m a y b e us e d if av ail a bl e. S elf-r e p ort e d v al u es ar e acc e pt a bl e.  
3 6 8  
•  W ei g ht  a n d h ei g ht  
3 6 9  
•  Bl o o d pr ess ur e  
3 7 0  
•  P uls e 
3 7 1  
•  T e m p er at ur e  
3 7 2  
•  Scr e e ni n g L a bs  
3 7 3  
•  H e m o gl o bi n A 1c  wit hi n p ast 6 m o nt hs or a v er a g e gl uc os e o n C G M  
3 7 4  
•  Hist or y of pr e g n a ncy or i nt e nt t o b ec o m e pr e g n a nt d uri n g t h e st u d y  
3 7 5  
•  C O VI D -1 9 v acci n ati o n  
3 7 6  
Scr e e ni n g  pr oc e d ur es  will  l ast  a p pr oxi m at el y  1 -2  h o urs.  Scr e e ni n g  c a n  b e  p erf or m e d  vi a  
3 7 7  
vi d e oc o nf er e nc e. O nc e all r es ults of t h e scr e e ni n g e v al u ati o ns ar e a v ail a bl e, a d ecisi o n will b e 
3 7 8  
m a d e t o d et er mi n e t h e p artici p a nt’s eli gi bility f or t h e st u d y or if o n e or m or e p art of t h e scr e e ni n g 
3 7 9  
will h a v e t o b e r e p e at e d. If at t h e first scr e e ni n g or r e p e at scr e e ni n g a n  excl usi o n ary c o n diti o n is 
3 8 0  
i d e ntifi e d, t h e p artici p a nt will b e excl u d e d fr o m p artici p ati o n wit h f oll o w u p a n d r ef err e d t o t h eir 
3 8 1  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 8  of 6 6  
 
pri m ar y c ar e p h ysici a n as n e e d e d. T h e st u d y p h ysici a n m a y el ect t o r escr e e n p artici p a nts if t h eir 
3 8 2  
cli nic al sit u ati o n c h a n g es.  
 
3 8 3  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 2 9  of 6 6  
 
C h a pt er 4:  R a n d o miz ati o n Visit    
3 8 4  
O nc e eli gi bilit y is m et, t h e p artici p a nt m ay c o nti n u e wit h r a n d o miz ati o n at t h e c o ncl usi o n of t h e 
3 8 5  
scr e e ni n g a p p oi nt m e nt. Usi n g a r a n d o miz e d bl ock d esi g n, t h e p artici p a nts will b e r a n d o ml y 
3 8 6  
assi g n e d t o eit h er o n e of t h e t w o tr e at m e nt gr o u ps.  Scr e e ni n g f ail ur es a n d st u d y dr o p o ut 
3 8 7  
p artici p a nts m a y b e r e pl ac e d.  
3 8 8  
 
3 8 9  
P artici p a nts will n ot b e r a n d o miz e d i n t h e Pil ot St u d y.  
3 9 0  
 
3 9 1  
A p pr oxi m at el y 3 0  p artici p a nts will b e r a n d o miz e d 1: 1 t o us e U SS Vir gi ni a or US S Vir gi ni a wit h SI -
3 9 2  
i nf or m e d b ol us c alc ul at or first . U p t o 7 0  p artici p a nts  m a y si g n t h e i nf or m e d c o ns e nt f or m.  
3 9 3  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 0  of 6 6  
 
C h a pt er 5:  St u d y E q ui p m e nt Tr ai ni n g  
3 9 4  
P artici p a nts will b e tr ai n e d o n t h e us e of t h e st u d y C G M aft er st u d y eli gi bility h as b e e n m et. 
3 9 5  
A d diti o n al  e q ui p m e nt tr ai ni n g m a y  b e gi n  at  arri v al t o  st u d y a d missi o n(s)  aft er  t h e  s yst e m  
3 9 6  
e q ui p m e nt h as b e e n p ut i n pl ac e . T h e p ur p os e of t his tr ai ni n g is t o i ntr o d uc e t h e st u d y i ns uli n 
3 9 7  
p u m p a n d st u d y C G M t o t h e p artici p a nt.  
3 9 8  
 
3 9 9  
A st u d y C G M will b e pr o vi d e d t o all p artici p a nts aft er m e eti n g st u d y eli gi bility. T h e p artici p a nts 
4 0 0  
will b e pr o vi d e d wit h C G M e q ui p m e nt a n d i nstr uct e d t o p l ac e t h e st u d y C G M ~2 4 -4 8 h o urs pri or 
4 0 1  
t o arri v al t o c a m p a n d us e t h e st u d y C G M o n a d ail y b asis. If t h e p artici p a nt h as pri or us e of t h e 
4 0 2  
C G M, r e -tr ai ni n g will b e s p ecific t o t h e i n di vi d u al. T h e st u d y t e a m will h a v e p artici p a nts w h o ar e 
4 0 3  
n ot  f a mili ar  wit h  t h e  st u d y  C G M  w atc h  t h e  D exc o m  o nli n e  tr ai ni n g  vi d e os  
4 0 4  
(htt ps:// w w w. d exc o m.c o m/tr ai ni n g -vi d e os ). St u d y st aff will s p ecific all y i d e ntify h o w al ar ms ar e 
4 0 5  
s et usi n g t h e a p p a n d t h e fr e q u e ncy t h at t h es e al ar ms r e p e at. P ar e nts m a y o pti o n all y us e t h e 
4 0 6  
D exc o m S h a r e A p p f or m o nit ori n g f or t h e at-h o m e us e of t h e C G M. A st u d y p h o n e m a y b e 
4 0 7  
pr o vi d e d f or t his p ur p os e.  
4 0 8  
 
4 0 9  
T h e st u d y t e a m will b e r es p o nsi bl e f or m o nit ori n g a n d m a n a gi n g t h e st u d y i ns uli n p u m p d uri n g 
4 1 0  
t h e st u d y a d missi o n(s) . T h e p artici p a nts will b e pr o vi d e d a q uick o v er vi e w o n its f u ncti o n ality . 
4 1 1  
 St u d y I ns uli n P u m p T o pics  
4 1 2  
T h e st u d y t e a m will assist t h e p artici p a nt i n pl aci n g t h e st u d y p u m p i nf usi o n sit e a n d will st art 
4 1 3  
t h e p artici p a nt o n t h e st u d y p u m p. T h e st u d y p u m p will b e pr o gr a m m e d b y t h e st u d y st aff b as e d 
4 1 4  
o n  t h e p artici p a nt’s h o m e p ar a m et ers , wi t h a 1 0 -2 0 % r e d ucti o n  of b as al r at e d et er mi n e d b y t h e 
4 1 5  
st u d y p h ysici a n t o acc o u nt f or i ncr e as e d p h ysic al acti vity at t h e c a m p. T h e p artici p a nt’s p ers o n al 
4 1 6  
p u m p a n d i nf usi o n sit e will b e r e m o v e d . 
4 1 7  
T h e  p artici p a nt  will  b e  i nstr uct e d  o n  pl aci n g  i nf usi o n  sit es,  c artri d g e/ pri mi n g  pr oc e d ur es,  
4 1 8  
c h ar gi n g t h e p u m p, n a vi g ati o n t hr o u g h m e n us, a n d b ol us pr oc e d ur es i ncl u di n g st o p pi n g a b ol us, 
4 1 9  
etc.  
4 2 0  
 Ot h er Iss u es  
4 2 1  
T h e p artici p a nt will b e i nstr uct e d t o n otify st u d y st aff if t h e y ex p eri e nc e a n y iss u es wit h t h e st u d y 
4 2 2  
d e vic es d uri n g t h e st u d y a d missi o n(s) . St aff will b e pr es e nt i n t h e e v e n t h at i ns uli n is d eli v er e d 
4 2 3  
b y a n y m e a ns ot h er t h a n t h e st u d y p u m p ( e. g. , i nj ecti o n of s u bc ut a n e o us i ns uli n vi a s yri n g e i n 
4 2 4  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 1  of 6 6  
 
t h e e v e nt of i nf usi o n sit e f ail ur e). If i ns uli n is d eli v er e d b y a n y m e a ns ot h er t h a n t h e st u d y p u m p, 
4 2 5  
cl os e d-l o o p m o d e will b e t ur n e d off f or a p pr oxi m at el y f o ur h o urs.  
4 2 6  
T h e p artici p a nt will b e as k e d t o al ert t h e st u d y cli nic al st aff f or a n y ill n ess t h at d e v el o ps d uri n g 
4 2 7  
us e of t h e st u d y s yst e m. P artici p a nts will als o al ert t h e st u d y st aff f or a n y t ec h nic al iss u es or 
4 2 8  
c o m p o n e nt disc o n n ecti o ns wit h t h e st u d y p u m p a n d/ or t h e Di As s yst e m.  
4 2 9  
A  gl uc a g o n  e m er g e ncy  kit  will  b e  a v ail a bl e  at  all  ti m es  d uri n g  t h e  st u d y  f or  us e  d uri n g 
4 3 0  
e m er g e nci es. Gl yc e mic Tr e at m e nt G ui d eli n es will b e a v ail a bl e f or st aff t o us e d uri n g t h e c a m p.  
4 3 1  
 O pti miz ati o n of I ns uli n P u m p S etti n gs  
4 3 2  
O pti miz ati o n of p u m p s etti n gs c a n occ ur at a n y ti m e d uri n g t h e st u d y p er t h e discr eti o n of t h e 
4 3 3  
st u d y p h ysici a n if t h er e ar e c o nc er ns r e g ar di n g r ec urri n g h y p o - or h y p er gl yc e mi a.  
4 3 4  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 2  of 6 6  
 
C h a pt er 6:  Pil ot St u d y   
4 3 5  
T h e Pil ot St u d y will b e p erf or m e d at a l oc al h ot el . T h e st u d y a d missi o n will t a k e u p t o 2 4 h o urs 
4 3 6  
wit h t h e i nt e nt of c oll ecti n g a p pr o pri at e s af ety d at a. Pil ot st u d y p artici p a nts ar e eli gi bl e t o e nr oll 
4 3 7  
i n t h e M ai n St u d y.  
4 3 8  
 
4 3 9  
T h er e will b e at l e ast t hr e e st u d y st aff pr es e nt at all ti m es at t h e st u d y sit e, at l e ast  o n e of w h o m 
4 4 0  
will b e cli nic al st aff ( e. g. , n urs e, p h ysici a n, n urs e pr actiti o n er). T h er e will b e a p hysici a n at t h e 
4 4 1  
h ot el or n e ar b y o n c all d uri n g t h e st u d y at all ti m es. I n a d diti o n, at l e ast o n e s e ni or e n gi n e er will 
4 4 2  
b e o n c all d uri n g t h e e ntir e a d missi o n.  P artici p a nts will b e r e m ot el y m o nit or e d by at l e ast o n e 
4 4 3  
st u d y t e a m m e m b er usi n g a w e b-b as e d r e m ot e m o nit ori n g s yst e m t h at h as b e e n pr e vi o usl y 
4 4 4  
est a blis h e d f or Di As. T h e w e b -b as e d r e m ot e m o nit ori n g s yst e m will dis pl a y r e al -ti m e i ns uli n 
4 4 5  
d eli v er y, C G M a n d ot h er s yst e m i nf or m ati o n t o all o w f or p ati e nt s af ety m o nit ori n g.  I n a d diti o n, 
4 4 6  
st u d y  t e a m  m e m b ers  will  b e  tr ai n e d  i n  all  pr ot oc ol  a n d  gl yc e mic  tr e at m e nt  g ui d eli n es  
4 4 7  
pr oc e d ur es.  T h e  cl os e d -l o o p  s yst e m  will  b e  m a n a g e d  b y  t h e  p artici p a nt  wit h  st u d y-st aff 
4 4 8  
s u p er visio n, p artic ul arl y at t h e ti m e of i ns uli n b ol us es. Gl uc a g o n f or t h e e m er g e ncy tr e at m e nt of 
4 4 9  
h y p o gl yc e mi a will b e a v ail a bl e o n -sit e.  
4 5 0  
 
4 5 1  
•  Pil ot p artici p a nts will b e c o nt act e d b y t h e st u d y t e a m a p pr oxi m at el y 4 8 h o urs pri or t o t h e 
4 5 2  
st u d y a d missi o n t o v erify t h e f oll o wi n g i nf or m ati o n: 
4 5 3  
•  C o nfir m t h at t h e p artici p a nt  will  i ns ert a st u dy C G M 2 4 -4 8 h o urs pri or t o t h e st u d y 
4 5 4  
a d missi o n  
4 5 5  
•  I n q uir e a b o ut a n y c h a n g es t o t h e p artici p a nt’s m e dic al hist or y  
4 5 6  
•  I n q uir e a b o ut t h e p artici p a nt’s p ossi bl e C O VI D-1 9  ex p os ur es a n d st u d y  r el at e d i niti al 
4 5 7  
C O VI D -1 9  t esti n g 
4 5 8  
•  D et er mi n e p u m p pr ofil e(s) t h e p artici p a nt is c urr e ntl y us i n g 
4 5 9  
•  V erify wit h t h e p artici p a nt  t h at t h e g o al CG M r e a di n g at ti m e of arri v al is l ess t h a n 2 0 0 
4 6 0  
m g/ dL  
4 6 1  
•  S h o ul d a n y c o nc er ns r e g ar di n g m e dic al hist or y, p u m p i nf or m ati o n, or u nf or es e e n iss u es 
4 6 2  
aris e,  t h e  a d missi o n  will  b e  c a nc ell e d  f or  t h at  p artici p a nt  at  t h e  discr eti o n  of  t h e  
4 6 3  
i n v esti g at or. 
4 6 4  
 
4 6 5  
P artici p a nts will arri v e at  t h e h ot el o n t h e first d a y of t h e a d missi o n. T h e st u d y t e a m will p erf or m 
4 6 6  
vit al si g ns a n d a n y c h a n g es t o t h e p artici p a nt’s m e dic al hist or y. A n y c h a n g es t o m e dic al hist or y 
4 6 7  
will b e c o m m u nic at e d t o t h e m e dic al p h ysici a n t o e ns ur e c o nti n u e d eli gi bility a n d p artici p ati o n. 
4 6 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 3  of 6 6  
 
A uri n e pr e g n a ncy t est will b e c oll ect e d if a p plic a bl e. T h e t est m ust b e n e g ati v e f or t h e p artici p a nt 
4 6 9  
t o c o nti n u e wit h t h e st u d y.  
4 7 0  
I n  t h e  e v e nt  t h at  t h e  p artici p a nt’s  C G M  r e a di n g  is  n ot  b et w e e n  8 0 -2 5 0  m g/ dL  or  k et o n e  
4 7 1  
c o nc e ntr ati o n  is ≥0. 6 m m ol/L pri or t o t h e  st u d y p u m p i niti ati o n, t h e st u d y  p h ysici a n  m a y  
4 7 2  
r ec o m m e n d c orr ecti v e acti o n as o utli n e d i n t h e Gl yc e mic Tr e at m e nt G ui d eli n es. St u d y p h ysici a n 
4 7 3  
m a y el ect t o c a nc el p artici p a nt’s p artici p ati o n i n t h e stu d y a d missi o n  if c o nc er n e d a b o ut t h eir 
4 7 4  
m e dic al s af et y. T his p artici p a nt will n ot b e r e pl ac e d.  
4 7 5  
T h e p artici p a nt’s h o m e  i ns uli n p u m p will b e disc o nti n u e d, a n d t h e st u d y  ins uli n p u m p will b e 
4 7 6  
i niti at e d. T h e st u d y t e a m will e ns ur e t h e pr o p er f u ncti o n of t h e C G M a n d  i ns uli n p u m p a n d will 
4 7 7  
c o n n ect b ot h of t h e m t o t h e Di As d e vic e . T h e g o al will b e t o i niti at e t h e st u dy s yst e m b y 
4 7 8  
a p pr oxi m at el y 9- 1 0 A M , r u n ni n g eit h er US S Vir gi ni a al o n e or US S Vir gi ni a  wit h t h e SI -i nf or m e d 
4 7 9  
s m art b ol us c alc ul at or i n t h e Di As pl atf or m.  
4 8 0  
T h e C G M us e d i n t h e st u d y is F D A -a p pr o v e d f or t h e n o n -a dj u ncti v e m e as ur e m e nt of bl o o d 
4 8 1  
gl uc os e (i. e. , t h e C G M r e a di n g c a n b e us e d f or i ns uli n d osi n g d ecisi o ns). T h e C G M r e a di n gs will 
4 8 2  
b e t h e pri m ar y s o urc e of bl o o d gl uc os e v al u es . T h er e ar e n o pr ot oc ol fi n g erstick bl o o d gl uc os e 
4 8 3  
m e as ur e m e nts ot h er t h a n at ti m es of C G M c ali br ati o n (if n ec ess ar y) a n d if dir ect e d b y t h e st u d y 
4 8 4  
t e a m. Fi n g erstick bl o o d gl uc os e m e as ur e m e nts m a y b e t a k e n w h e n e v er p artici p a nts ex p eri e nc e 
4 8 5  
s y m pt o ms, if t h e C G M gl uc os e is s us p ect e d t o b e err o n e o us, or a n y ti m e t h e p artici p a nt w o ul d 
4 8 6  
li k e t o b e r e ass ur e d.  
4 8 7  
 
4 8 8  
P artici p a nts will e at st u d y-pr o vi d e d m e als d uri n g t h e a d missi o n. T h e esti m at e d ti m e of m e als will 
4 8 9  
b e 8  A M , 12: 3 0  P M, a n d 6 P M.   
4 9 0  
 
4 9 1  
St u d y st aff will c o nfir m t h e c ar b o h y dr at e c o nt e nt of all m e als a n d s n acks pri or t o e nt eri n g i nt o 
4 9 2  
t h e  b ol us  c alc ul at or. P artici p a nts  will b e  r e q uir e d  t o  c o ns u m e  a  mi ni m u m of 4 0  gr a ms  of  
4 9 3  
c ar b o h y dr at e f or e ac h m e al. All m e al a n d c orr ecti o n b ol us e s will b e b as e d o n C G M r e a di n gs. 
4 9 4  
 
4 9 5  
P artici p a nts will b e fr e e t o e n g a g e i n l o w-i nt e nsity acti vity ( w al ki n g) d uri n g t h e m or ni n g a n d 
4 9 6  
aft er n o o n h o urs. P artici p a nts will e nj o y  q ui et acti viti es i n t h e e v e ni n g.  
4 9 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 4  of 6 6  
 
 
4 9 8  
Disc h ar g e wi ll b e at a p proxi m at el y 1 0 A M  if t h e C G M is b et w e e n 8 0 a n d 2 5 0 m g/ dL a n d k et o n es 
4 9 9  
< 0. 6 m m ol/L. Ot h er wis e, t h e st u d y t e a m will r ef er e nc e t h e Gl yc e mic Tr e at m e nt G ui d eli n es u ntil 
5 0 0  
t h e n e e d e d crit eri a f or disc h ar g e ar e m et.  
5 0 1  
A q u alifi e d cli nic al st u d y t e a m m e m b er ( e. g. , M D, N P, C D E) will ass ess a n d disc uss t h e tr a nsiti o n 
5 0 2  
b ack t o us u al c ar e wit h t h e st u d y p artici p a nt .    
5 0 3  
P artici p a nts will b e as k e d t o c o nti n u e m o nit ori n g k et o n e l e v els f or 2 4 -4 8 h o urs aft er t h e h ot el 
5 0 4  
a d missi o n. Uri n e k et o n e s u p pli es m a y b e pr o v i d e d f or t his t esti ng.  
5 0 5  
 
5 0 6  
A p pr oxi m at el y 7 2 h o urs aft er t h e st u d y a d missi o n, t h e st u d y t e a m will c o nt act t h e p artici p a nt vi a 
5 0 7  
p h o n e/ e m ail/t ext t o ass ess f or a n y a d v ers e e v e nts, a d v ers e d e vic e eff ects, a n d d e vic e iss u es .  
5 0 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 5  of 6 6  
 
C h a pt er 7:  M e dic al M o nit or  
5 0 9  
 
5 1 0  
T h e M e dic al M o nit or  (M M ) will b e pr o vi d e d all a d v ers e e v e nt d at a fr o m t h e tri al o ns et t hr o u g h 
5 1 1  
t h e st u d y a d missi o n(s)  f or r e vi e w. T h e  g o al is t o pr o vi d e at l e ast 7 5 % of t h e d at a t o t h e M M f or 
5 1 2  
r e vi e w. R e pl aci n g dr o p p e d st u d y p artici p a nts will n ot b e r e q uir e d i n t h e Pil ot St u d y. T h e M M will 
5 1 3  
r e vi e w d at a r el at e d t o i n di vi d u al st o p pi n g crit eri a as d et ail e d i n t h e st u d y pr ot oc ol.  
5 1 4  
 
5 1 5  
Aft er  t h eir  r e vi e w,  t h e  M M 
c a n  r ec o m m e n d  t h at  t h e  c urr e nt  st u d y  c o nti n u e  wit h o ut  
5 1 6  
m o dific ati o n, c o nti n u e wit h s p ecifi e d m o dific ati o ns, disc o nti n u e o n e or m or e ar ms of t h e st u d y, 
5 1 7  
or h alt or m o dify t h e st u d y u ntil m or e i nf or m ati o n is a v ail a bl e . 
5 1 8  
T h e M M m a y r ec o m m e n d m o dific ati o ns t o i n di vi d u al st o p pi n g r ul es if a d diti o n al s af ety c o nc er ns 
5 1 9  
aris e d uri n g fr o m t h eir c o nti n ui n g r e vi e ws of t h e st u d y d at a .  
5 2 0  
T h e st u d y a d missi o n(s)  will n ot b e r e p e at e d u nl ess r e q uir e d b y t h e M M .  
5 2 1  
 
5 2 2  
A M M will r e vi e w c o m pil e d s af et y d at a at t h e c o ncl usi o n of t h e tri al. I n a d diti o n, t h e M M  will 
5 2 3  
r e vi e w all D K A a n d s e v er e h y p o gl yc e mi a irr es p ecti v e of r el at e d n ess t o st u d y d e vic e us e, a n d all 
5 2 4  
s eri o us e v e nts (i ncl u di n g U A D Es) r el at e d t o st u d y d e vic e us e at t h e ti m e of occ urr e nc e. T h e M M 
5 2 5  
als o will b e i nf or m e d of a n y A D Es n ot m e eti n g crit eri a f or a U A D E if t h e St u d y PI r e q u ests t h e M M 
5 2 6  
r e vi e w. T h e M M c a n r e q u est m o dific ati o ns t o t h e st u d y pr ot oc ol or s us p e nsi o n or o u tri g ht 
5 2 7  
st o p p a g e of t h e st u d y if d e e m e d n ec ess ary b as e d o n t h e t ot ality of s af ety d at a a v ail a bl e.  
5 2 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 6  of 6 6  
 
C h a pt er 8:  M ai n St u d y   
5 2 9  
St u d y p artici p a n ts will b e scr e e n e d pri or t o arri v al t o c a m p.  
5 3 0  
 
5 3 1  
St u d y st aff will b e pr es e nt or o n c all at all ti m es d uri n g  t h e st u d y a d missi o n(s) , i ncl u di n g st u d y 
5 3 2  
p h ysici a ns, st u d y n urs es, t ec h nic al s u p p ort st aff , a n d s e ni or e n gi n e ers. At l e ast t w o m e dic all y -
5 3 3  
tr ai n e d st u d y st aff m e m b ers will b e pr es e nt o n sit e at all ti m es, i ncl u di n g at l e ast o n e st u d y 
5 3 4  
p h ysici a n  a n d o n e n urs e . C a m p p ers o n n el will dir ect  t h e r ecr e ati o n acti viti es wit h st u d y st aff 
5 3 5  
s u p p ort.  
5 3 6  
 
5 3 7  
P artici p a nts will b e c o nt act e d b y t h e st u d y t e a m 2 4 -4 8 h o urs pri or t o st u d y a d missi o n(s) . T h e 
5 3 8  
st u d y t e a m will v erify t h e f oll o wi n g i nf or m ati o n: 
5 3 9  
•  T h e p artici p a nt will i ns ert n e w C G M s e ns or a p pr oxi m at el y 2 4 -4 8 h o urs pri or t o t h e c a m p  
5 4 0  
•  I n q uir e a b o ut a n y c h a n g es t o t h e p artici p a nt’s m e dic al hist or y 
5 4 1  
•  C o nfir m t h e p artici p a nt h as c o m pl et ed C O VI D -1 9 P C R t est as d escri b e d i n s ecti o n 9. 1. 3  
5 4 2  
•  C o nfir m t h e p artici p a nt d o es n ot c urr e ntly h a v e a n y s y m pt o ms of C O VI D-1 9 ( e. g., f e v er, 
5 4 3  
s h ort n ess of br e at h, u n ex p ect e d l oss of t ast e or s m ell) 
5 4 4  
•  C o nfir m t h e p artici p a nt h as n’t h a d k n o w n c o nt act wit h C O VI D -p ositi v e i n di vi d u al wit hi n 
5 4 5  
7 d a ys of a n y st u d y a d missi o n(s)  
5 4 6  
•  C o nfir m t h e p artici p a nts h as n’t h a d a p ositi v e C O VI D -1 9 t est r es ults wit hi n 1 0 d a ys of 
5 4 7  
a n y st u d y a d missi o n( s) 
5 4 8  
•  C o nfir m p u m p p ar a m et er pr ofil es t h e p artici p a nt is c urr e ntl y usi n g  
5 4 9  
•  V erify wit h t h e p artici p a nt  t h at t h e g o al C G M r e a di n g at t h e ti m e of arri v al is < 2 0 0 m g/ dL 
5 5 0  
•  S h o ul d a n y c o nc er ns r e g ar di n g m e dic al hist or y, p u m p i nf or m ati o n, or u nf or es e e n iss u es 
5 5 1  
aris e, t h e a d missi o n(s)  will b e c a nc ell e d at t h e discr eti o n of t h e i n v esti g at or  
5 5 2  
 
5 5 3  
P artici p a nts will arri v e at c a m p o n t h e first d a y of e ac h st u d y a d missi o n(s) . 
5 5 4  
 P artici p a nt C h ec k -i n a n d V erific ati o n  
5 5 5  
At ti m e of c h eck -i n, p artici p a nts will u n d er g o t h e f oll o wi n g pr oc e d ur es/t ests: 
5 5 6  
•  Vit al si g ns will b e m e as ur e d.  
5 5 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 7  of 6 6  
 
•  It will b e c o nfir m e d t h at t h e p artici p a nt d o es n ot c urr e ntl y ex p eri e nc e a n y s y m pt o ms of 
5 5 8  
C O VI D -1 9; h as n ot h a d a n y c o nt act wit h a C O VI D-p ositi v e i n di vi d u al i n  t h e pr e vi o us  7 d a ys; 
5 5 9  
a n d h as n ot h a d a p ositi v e C O VI D -1 9 t est r es ult i n t h e pr e vi o us 1 0 d a ys .  
5 6 0  
•  F e m al e p artici p a nt s  of  c hil d b e ari n g  p ot e nti al  will  b e  r e q uir e d  t o  c o m pl et e  a  uri n e  
5 6 1  
pr e g n a ncy t est. If p ositi v e, p artici p a nt will b e disc o nti n u e d fr o m t h e st u d y.  
5 6 2  
•  C o nfir m t h at t h e p artici p a nt br o u g ht his/ h er p ers o n al i ns uli n a n d r e g ul ar m e dic ati o ns.  
5 6 3  
•  P artici p a nts will b e as k e d t o p erf or m a bl o o d k et o n e fi n g erstick. If k et o n es ar e n ot < 0. 6  
5 6 4  
m m ol/L,  st u d y  st aff  s h o ul d  tr e at  wit h  or al  h y dr ati o n  a n d,  if  n e e d e d,  t h e  Gl yc e mic  
5 6 5  
Tr e at m e nt G ui d eli n es will b e f oll o w e d; k et o n es will b e r e -c h eck e d e v er y h o ur u ntil < 0. 6  
5 6 6  
m m ol/L.  T h e p artici p a nt will b e a bl e t o b e gi n p artici p ati o n i n t h e c a m p acti viti es o nc e t h e 
5 6 7  
C G M r e a ds b et w e e n 8 0 -2 5 0 m g/ dL a n d k et o n es ar e < 0. 6  m m ol/L.  
5 6 8  
 Assi g n m e nt t o R a n d o miz ati o n Gr o u p  
5 6 9  
P artici p a nts will b e pl ac e d o n t h e st u d y C G M a n d i ns uli n p u m p a n d t h e Di As s yst e m i m pl e m e nti n g 
5 7 0  
t h e al g orit h m of t h e s p ecific ar m ( ex p eri m e nt al or c o ntr ol) will b e c o n n ect e d t o t h e p artici p a nt’s 
5 7 1  
C G M tr a ns mitt er vi a Bl u et o ot h c o n n ecti o n. T h e st u d y t e a m will e ns ur e t h e pr o p er f u ncti o ni n g of 
5 7 2  
t h e C G M a n d i ns uli n p u m p. 
5 7 3  
 
5 7 4  
 G e n er al A d missi o n(s)  O v er vi e w  
5 7 5  
D uri n g t h e e ntir e d ur ati o n of e ac h st u dy a d missi o n(s) , t h e st u d y t e a m will r e m ot el y m o nit or 
5 7 6  
p artici p a nts’ r e al -ti m e C G M r e a di n gs. St u d y t e a m m e m b ers tr ai n e d i n all pr ot oc ol i nt er v e nti o ns 
5 7 7  
(i ncl u di n g t h e h y p o gl yc e mia a n d h y p er gl yc e mi a s af ety pr ot oc ols) will b e wit h t h e p artici p a nts at 
5 7 8  
all ti m es d uri n g c a m p acti viti es, wit h e ac h m e m b er r e m ot el y c o n n ect e d t o t h e p artici p a nts C G M 
5 7 9  
d at a. I n a d diti o n, a st u d y t e a m p h ysici a n tr ai n e d i n all pr ot oc ol a n d gl yc e mic tr e at m e nt g u i d eli n e 
5 8 0  
pr oc e d ur es will b e a v ail a bl e at a c e ntr al l oc ati o n o n c a m p pr o p erty .  
5 8 1  
All r ecr e ati o n al acti viti es will b e m a n a g e d b y t h e st aff a n d c o u ns ell ors at C a m p H oli d a y Tr ails  wit h 
5 8 2  
st u d y st aff s u p er visi o n. 
5 8 3  
D uri n g t h e o v er ni g ht h o urs, st u d y st aff will b e acti v el y m o nit ori n g r e al -ti m e C G M d at a f or all 
5 8 4  
p artici p a nts wit h dir ect acc ess t o t h e p artici p a nts.  
5 8 5  
 D e vic e Pr oc e d ur es f or P artici p a nts  
5 8 6  
T h e st u d y i ns uli n p u m p a n d Di As d e vic e will b e pr o vi d e d u p o n arri v al t o t h e c a m p. All p artici p a nts 
5 8 7  
will c o nti n u e t o w e ar t h e st u d y C G M. W h e n p artici p a nts cr oss o v er i nt o t h e ot h er tr e at m e nt 
5 8 8  
gr o u p, t h e y will c o nti n u e t o w e ar t h e s a m e st u d y C G M a n d st u d y i ns uli n p u m p wit h t h e c h a n g e 
5 8 9  
o nl y m a d e t o t h e s oft w ar e t h at t h e s yst e m is r u n ni n g .  
5 9 0  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 8  of 6 6  
 
P artici p a nts will h a v e all e q ui p m e nt wit h  t h e m at all ti m es. St u d y st aff will b e a v ail a bl e at all ti m es 
5 9 1  
t o ass ur e pr o p er us e of all st u d y e q ui p m e nt. 
5 9 2  
 M e al R e q uir e m e nts  
5 9 3  
St u d y st aff will c o nfir m t h e c ar b o h y dr at e c o nt e nt of all m e als a n d s n acks pri or t o e nt eri n g i nt o 
5 9 4  
t h e b ol us c alc ul at or. P artici p a nt s  will b e  r e q uir e d  t o  c o ns u m e  a  mi ni m u m of 4 0  gr a ms  of  
5 9 5  
c ar b o h y dr at e f or e ac h m e al. All m e al a n d c orr ecti o n b ol us es will b e b as e d o n C G M r e a di n gs.  
5 9 6  
 P artici p a nt’s A d missi o n(s)  Iti n er ar y  
5 9 7  
P artici p a nts will g e n er all y f oll o w t h e b el o w sc h e d ul e d uri n g e ac h st u d y a d missi o n(s) .  
5 9 8  
P artici p a nts will g e n er all y f oll o w t h e b el o w sc h e d ul e d uri n g t h e 6 d a y / 5 ni g h a d missi o n:  
5 9 9  
C a m p C h eck -i n ( all ti m es ar e esti m at es): 
6 0 0  
1 3 0 0 -1 6 0 0: C h eck -i n a n d st u d y e q ui p m e nt c o n n ecti o n. P artici p a nts will u n d er g o t h e c h eck-i n 
6 0 1  
pr oc e d ur es as list e d i n s ecti o n 8. 3 a n d st art us e of st u d y e q ui p m e nt.  
6 0 2  
1 6 0 0 -1 8 0 0: Aft er n o o n C a m p Acti vit y p er C a m p st aff  
6 0 3  
1 8 0 0: Di n n er  
6 0 4  
1 9 0 0 -2 0 3 0 : Ev e ni n g C a m p Acti vit y p er C a m p St aff  
6 0 5  
2 0 3 0: B e dti m e s n ack  
6 0 6  
2 1 0 0 -2 3 0 0: Fr e e ti m e/ B e dti m e  
6 0 7  
D a y 1 & 2  
6 0 8  
0 8 0 0 -0 9 0 0: Br e a kf ast  
6 0 9  
0 9 0 0 -1 2 0 0: M or ni n g C a m p Acti viti es. P artici p a nts will b e gi n t h e acti viti es if his/ h er C G M r e a ds 
6 1 0  
> 9 0 m g/ dL. If ≤ 9 0 m g/ dL, t h e Gl yc e mic Tr e at m e nt G ui d eli n es wi ll b e f oll o w e d u ntil cl e ar e d t o 
6 1 1  
b e gi n acti vit y. A n o pti o n al m or ni n g s n ack will b e pr o vi d e d b et w e e n acti viti es.  
6 1 2  
1 2 3 0 -1 3 3 0: L u nc h  
6 1 3  
1 3 3 0 -1 5 0 0: R est H o ur  
6 1 4  
1 5 0 0: Aft er n o o n S n ack  
6 1 5  
1 5 1 5 -1 7 1 5: Aft er n o o n C a m p Acti viti es. P artici p a nts will b e gi n t h e aft er n o o n acti vity  if his/ h er 
6 1 6  
C G M r e a ds > 9 0 m g/ dL. If ≤ 9 0 m g/ dL, t h e Gl yc e mic Tr e at m e nt G ui d eli n es will b e f oll o w e d u ntil 
6 1 7  
cl e ar e d t o b e gi n acti vit y. 
6 1 8  
1 7 3 0 -1 8 3 0: Di n n er  
6 1 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 3 9  of 6 6  
 
1 8 3 0 -2 0 3 0: Ev e ni n g C a m p Acti vit y p er C a m p St aff  
6 2 0  
2 0 3 0: B e dti m e s n ack  
6 2 1  
2 1 0 0 -2 3 0 0: Fr e e ti m e/ B e dti m e  
6 2 2  
D a y 3 & 4 
6 2 3  
Pri or t o br e a kf ast o n t h e m or ni n g of D a y 3, all p artici p a nts will cr oss o v er i nt o t h e ot h er tr e at m e nt 
6 2 4  
ar m. T h e m or ni n g a n d aft er n o o n acti viti es t h at t h e p artici p a nts p erf or m e d o n t h e first a n d 
6 2 5  
s ec o n d d a ys of c a m p a n d t h e sc h e d ul es will b e i d e ntic al o n t h es e d a ys (i. e., D a y 3 will b e t h e s a m e 
6 2 6  
as D a y 1 a n d D a y 4 will b e t h e s a m e as D ay 2). Pr o vi d e d m e als will als o b e si mil ar wit h r e g ar ds t o 
6 2 7  
c ar b o h y dr at e c o nt e nt.  
6 2 8  
D a y 5  
6 2 9  
0 8 0 0 -0 9 0 0: Br e a kf ast  
6 3 0  
 
6 3 1  
P artici p a nts will g e n er all y f oll o w t h e b el o w sc h e d ul e d uri n g t h e 4 d a y / 3 ni g ht a d missi o n:  
6 3 2  
D a y 1 a n d D a y 5  (i. e., first d a y of e ac h c a m p a d missi o n ) 
6 3 3  
1 3 0 0 -1 6 0 0: C h eck -i n a n d st u d y e q ui p m e nt c o n n ecti o n. P artici p a nts will u n d er g o t h e c h eck-in 
6 3 4  
pr oc e d ur es as list e d i n s ecti o n 8. 3 a n d st art us e of st u d y e q ui p m e nt .  
6 3 5  
1 6 0 0 -1 8 0 0: Aft er n o o n c a m p acti vit y p er c a m p st aff 
6 3 6  
1 8 0 0 -1 9 0 0 : Di n n er 
6 3 7  
1 9 0 0 -2 2 0 0 : Ev e ni n g c a m p acti vit y p er c a m p st aff 
6 3 8  
2 2 0 0 - 2 23 0: Pr e p ar ati o n f or b e dti m e  a n d o pti o n al c ar b -fr e e b e dti m e s n ack  
6 3 9  
D a y s 2 &3 a n d D a ys 6 & 7  (i. e., s ec o n d a n d t hir d d a y of e ac h c a m p a d missi o n) 
6 4 0  
0 8 0 0 -0 9 0 0: Br e a kf ast  
6 4 1  
0 9 0 0 -1 2 3 0 : M or ni n g c a m p acti viti es. P artici p a nts will b e gi n t h e acti viti es if t h eir C G M r e a ds  >9 0 
6 4 2  
m g/ dL . If ≤ 90 m g/ dL, t h e Gl yc e mic Tr e at m e nt G ui d eli n es will b e f oll o w e d u ntil cl e ar e d t o b e gi n 
6 4 3  
acti vit y.   
6 4 4  
1 2 3 0 -1 3 3 0: L u nc h  
6 4 5  
1 3 3 0 -1 4 3 0 : R est H o ur 
6 4 6  
1 4 3 0 -1 5 0 0 : O pti o n al aft er n o o n s n ack 
6 4 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 0  of 6 6  
 
1 5 0 0 -1 7 3 0 : Aft er n o o n c a m p acti viti es. P artici p a nts will b e gi n t h e aft er n o o n acti vity  if t h eir C G M 
6 4 8  
r e a ds >9 0 m g/ dL . If ≤ 9 0 m g/ dL, t h e Gl yc e mic Tr e at m e nt G ui d eli n es will b e f oll o w e d u ntil cl e ar e d 
6 4 9  
t o b e gi n acti vit y. 
6 5 0  
1 7: 3 0 -1 8 0 0: S h o w er ti m e  
6 5 1  
1 8 0 0 -1 9 0 0 : Di n n er 
6 5 2  
1 9 0 0 -2 2 0 0 : Ev e ni n g c a m p acti vit y p er ca m p st aff 
6 5 3  
2 2 0 0 -2 2 3 0: Pr e p ar ati o n f or b e dti m e , o pti o n al c ar b -fr e e b e dti m e s n ack, a n d b ack t o t e nts  
6 5 4  
D a y 4 a n d D a y 8  
6 5 5  
0 8 0 0 -0 9 0 0: Br e a kf ast  
6 5 6  
0 9 0 0 -1 2 0 0 : Disc h ar g e pr oc e d ur es wit h s u p p ort c a m p acti viti es a n d l u nc h pr o vi d e d if n e e d e d 
6 5 7  
 
6 5 8  
Disc h ar g e will b e at a p pr oxi m at el y 0 9 0 0 -1 2 0 0  if t h e C G M ar e b et w e e n 8 0 -2 5 0 m g/ dL a n d k et o n e 
6 5 9  
v al u es < 0. 6 m m ol/L will b e n e e d e d at ti m e of disc h ar g e.  Ot h er wis e, t h e st u d y t e a m will r ef er e nc e 
6 6 0  
t h e Gl yc e mic Tr e at m e nt G ui d eli n es  u ntil t h e n e e d e d crit e ri a f or disc h ar g e ar e m et.   
6 6 1  
A q u alifi e d cli nic al st u d y t e a m m e m b er ( e. g., M D, N P, C D E) will ass ess a n d disc uss t h e tr a nsiti o n 
6 6 2  
b ack t o us u al c ar e wit h t h e st u d y p artici p a nt.   P artici p a nts m a y c o nti n u e w e ari n g t h e st u d y C G M 
6 6 3  
b et w e e n a d missi o n # 1 a n d a d missi o n # 2 if p artici p ati n g i n t h e  4 d a y/ 3 ni g ht c a m p.  
6 6 4  
P artici p a nts  will  b e  as k e d  t o  c o nti n u e  m o nit ori n g  k et o n e  l e v els  f or  2 4 -4 8  h o urs  aft er  t h e  
6 6 5  
a d missi o n(s) . Uri n e k et o n e s u p pli es m a y b e pr o vi d e d f or t his t esti n g. 
6 6 6  
 
6 6 7  
A p pr oxi m at el y 7 2 h o urs aft er t h e st u d y a d missi o n(s) , t h e st u d y t e a m will c o nt act t h e p artici p a nt 
6 6 8  
vi a p h o n e/ e m ail/t ext t o ass ess f or a n y a dv ers e e v e nts, a d v ers e d e vic e eff ects, a n d d e vic e iss u es.  
6 6 9  
P ost- disc h ar g e g ui d eli n es r el at e d t o C O VI D ar e o utli n e d i n s ecti o n 1 1. 4.  
6 7 0  
 
6 7 1  
If t h e C G M si g n al b ec o m es u n a v ail a bl e f or m or e t h a n 2 0 mi n ut es c o ns ec uti v el y, t h e H CL s yst e m 
6 7 2  
will n ot o p er at e t o a ut o m atic all y a dj ust i ns uli n . If t h e C G M is n ot c o n n ect e d, t h e s yst e m will 
6 7 3  
r e v ert t o us u al f u ncti o n of t h e p u m p a n d d eli v er i ns uli n wit h t h e i ns uli n d osi n g p ar a m et ers 
6 7 4  
pr o gr a m m e d  i n  t h e  s yst e m f or  t h at  i n di vi d u al.  R es u m pti o n  of  Cl os e d-L o o p  will  
6 7 5  
occ ur  a ut o m atic all y o nc e C G M si g n al is av ail a bl e a g ai n.  If t h e st u d y s yst e m is u n a bl e t o acti v at e 
6 7 6  
H CL  f or a n y r e as o n, t h e p u m p will a ut o m atic all y r e v ert t o pr e -pr o gr a m m e d b as al i ns uli n d eli v er y 
6 7 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 1  of 6 6  
 
wit h o ut a n y n e e d f or i nstr ucti o n fr o m t h e us er.  St u d y st aff will b e a v ail a bl e at all ti m es t o assist 
6 7 8  
wit h a n y iss u es i n c o n n ecti vit y t h at aris e.  
 
6 7 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 2  of 6 6  
 
C h a pt er 9:  T esti n g Pr oc e d ur es  
6 8 0  
 
6 8 1  
 H b A 1c  
6 8 2  
•  H b A 1c l e v el m a y b e m e as ur e d b y st u d y t e a m usi n g t h e D C A 2 0 0 0, a c o m p ar a bl e p oi nt 
6 8 3  
of c ar e d e vic e  at st u d y a d missi o n # 1 .  
6 8 4  
 Pr e g n a nc y T est  
6 8 5  
•  Pil ot st u d y a d missi o n:  A uri n e pr e g n a ncy t est will b e r e q uir e d f or w o m e n w h o ar e i n 
6 8 6  
c hil d birt h p ot e nti al at t h e st u d y a d missi o n. T est m ust b e n e g ati v e t o p artici p at e i n t h e 
6 8 7  
st u d y.  
6 8 8  
•  A uri n e pr e g n a ncy t est will b e r e q uir e d f or w o m e n of c hil d b e ari n g p ot e nti al at t h e 
6 8 9  
ti m e of st u d y a d missi o n(s) . T est m ust b e n e g ati v e t o p artici p at e i n t h e st u d y.  
6 9 0  
 C O VI D- 1 9 T est   
6 9 1  
•  M ai n st u d y a d missi o n(s) : A C O VI D-1 9 P C R t est will b e r e q uir e d f or p artici p a nts a n d 
6 9 2  
st aff 4 8 -7 2 h o urs pri or t o t h e st u d y a d missi o n(s) . P artici p a nts a n d st aff wit h a p ositiv e 
6 9 3  
t est r es ult wit hi n 1 0 d a ys  of t h e c a m p will b e excl u d e d fr o m t h e st u d y a d missi o n(s) .   
6 9 4  
•  A n y a p p e ar a nc e of C O VI D -1 9 s y m pt o ms i n p artici p a nts or st aff m e m b ers aft er t h e 
6 9 5  
m a n d at or y pr e -a d missi o n C O VI D -1 9 P C R t est will r es ult i n disc h ar g e fr o m t h e st u d y 
6 9 6  
a d missi o n(s) .  
 
6 9 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 3  of 6 6  
 
C h a pt er 1 0:  Ris ks Ass oci at e d wit h Cli nic al Tri al  
6 9 8  
 
6 9 9  
Ris ks a n d B e n efits ar e d et ail e d b el o w. L oss of c o nfi d e nti ality is a p ot e nti al ris k; h o w e v er, d at a ar e 
7 0 0  
h a n dl e d t o mi ni miz e t his ris k . Hy p o gl yc e mi a, h y p er gl yc e mi a a n d k et o n e f or m ati o n ar e al w a ys a 
7 0 1  
ris k i n p artici p a nts wit h T 1 D  a n d p artici p a nts will b e m o nit or e d f or t h es e s y m pt o ms.  
7 0 2  
 Fi n g erstic k Ris ks  
7 0 3  
A b o ut 1 dr o p of bl o o d will b e r e m o v e d b y fi n g erstick f or m e as uri n g bl o o d s u g ars a n d s o m eti m es 
7 0 4  
H b A 1c or ot h er t ests. T his is a st a n d ar d m et h o d us e d t o o bt ai n bl o o d f or r o uti n e h os pit al 
7 0 5  
l a b or at or y t ests. P ai n is c o m m o n at t h e ti m e of l a nci n g . I n a b o ut 1 i n 1 0 c as es, a s m all a m o u nt of 
7 0 6  
bl e e di n g u n d er t h e s ki n will pr o d uc e a br uis e . A s m all sc ar m a y  p ersist f or s e v er al w e e ks . T h e ris k 
7 0 7  
of l oc al i nf ecti o n is l ess t h a n 1 i n 1 0 0 0 . T his s h o ul d n ot b e a si g nific a nt c o ntri b ut or t o ris ks i n t his 
7 0 8  
st u d y as fi n g er sticks ar e p art of t h e us u al c ar e f or p e o pl e wit h di a b et es. 
7 0 9  
 S u bc ut a n e o us C at h et er Ris ks ( C G M)  
7 1 0  
P art ici p a nts usi n g t h e C G M will b e at l o w ris k f or d e v el o pi n g a l oc al s ki n i nf ecti o n at t h e sit e of 
7 1 1  
t h e s e ns or n e e dl e pl ac e m e nt. If a c at h et er is l eft u n d er t h e s ki n f or m or e t h a n 2 4 h o urs it is 
7 1 2  
p ossi bl e t o g et a n i nf ecti o n w h er e it g o es i nt o t h e s ki n, wit h s w elli n g, r e d n ess a n d p ai n . T h er e 
7 1 3  
m a y b e bl e e di n g w h er e t h e c at h et er is p ut i n a n d bl e e di n g u n d er t h e s ki n c a us es a br uis e ( 1 i n 1 0 
7 1 4  
ris k). 
7 1 5  
St u d y st aff s h o ul d v er b all y al ert t h e p artici p a nt t h at o n r ar e occ asi o ns, t h e C G M m a y br e a k a n d 
7 1 6  
l e a v e a s m all p orti o n of t h e s e ns or u n d er t h e s ki n t h at m a y c a us e r e d n ess, s w elli n g, or p ai n at 
7 1 7  
t h e i ns erti o n sit e. T h e p artici p a nt s h o ul d b e f urt h er i nstr uct e d t o n otify t h e st u d y c o or di n at or 
7 1 8  
i m m e di at el y if t his occ urs. 
7 1 9  
 Ris ks of H y p o gl yc e mi a  
7 2 0  
As wit h a n y p ers o n h a vi n g T 1 D  a n d usi n g i ns uli n, t h er e is al w a ys a ris k of h a vi n g a l o w bl o o d s u g ar 
7 2 1  
( h y p o gl yc e mi a). T h e fr e q u e ncy of h y p o gl yc e mi a s h o ul d b e n o m or e a n d p ossi bly l ess t h a n it 
7 2 2  
w o ul d b e as p art of d ail y li vi n g . S y m pt o ms of h y p o gl yc e mi a c a n i ncl u d e s w e ati n g, jitt eri n ess , a n d 
7 2 3  
n ot f e eli n g w ell . J ust as at h o m e, t h er e is t h e p ossi bility of f ai nti n g or s eiz ur es (c o nv ulsi o ns) a n d 
7 2 4  
t h at f or a f e w d a ys t h e p artici p a nt m a y n ot b e as a w ar e of s y m pt o ms of h y p o gl yc e mi a. A C G M 
7 2 5  
f u ncti o ni n g p o orl y a n d si g nific a ntl y o v er -r e a di n g gl uc os e v al u es c o ul d l e a d t o i n a p pr o pri at e 
7 2 6  
i ns uli n d eli v er y. 
7 2 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 4  of 6 6  
 
 Ris ks of H y p er gl yc e mi a  
7 2 8  
Hy p er gl yc e mi a a n d k et o n e mi a c o ul d occ ur if i ns uli n d eli v er y is att e n u at e d or s us p e n d e d f or a n 
7 2 9  
ext e n d e d p eri o d or if t h e p u m p or i nf usi o n s et is n ot w or ki n g pr o p erl y . A C G M f u ncti o ni n g p o orl y 
7 3 0  
a n d si g nific a ntl y u n d er -r e a di n g gl uc os e v al u es c o ul d l e a d t o i n a p pr o pri at e s us p e nsi o n of i ns uli n 
7 3 1  
d eli v er y.  
7 3 2  
 Ris ks of D e vic e R e us e  
7 3 3  
P artici p a nt will b e i nf or m e d t h at F D A or r el e v a nt n ati o n al a ut h oriti es h a v e a p pr o v e d t h e i ns u li n 
7 3 4  
p u m p, C G M, gl uc o m et er a n d k et o n e m et er f or si n gl e us e a n d t h at b y usi n g t h e m a m o n g m ulti pl e 
7 3 5  
p ati e nts, bl o o d b or n e p at h o g e ns (i. e. H e p atitis B) m a y b e s pr e a d t hr o u g h t h e us e of m ulti pl e 
7 3 6  
us ers.  
7 3 7  
T h e st u d y C G M s yst e m is l a b el e d f or si n gl e us e o nl y. T h e s e ns or (t h e c o m p o n e nt of t h e s yst e m 
7 3 8  
t h at e nt ers t h e s ki n) will b e si n gl e us e o nl y. T h e tr a ns mitt er a n d r ec ei v er m a y b e r e us e d d uri n g 
7 3 9  
t h e st u d y aft er cl e a ni n g t h e d e vic e usi n g a h os pit al-a p pr o v e d cl e a ni n g pr oc e d ur e. T h e tr a ns mitt er 
7 4 0  
is att ac h e d t o t h e s e ns or b ut d o es n ot e nt er t h e s ki n a n d t h e r ec ei v er, if us e d, is a h a n d -h el d 
7 4 1  
d e vic e.  
7 4 2  
T h e st u d y i ns uli n p u m p s ar e  l a b el e d f or si n gl e-p ati e nt us e. D uri n g t h e st u d y, t his d e vic e m a y b e 
7 4 3  
r e us e d  aft er  cl e a ni n g  a d h eri n g  t o  a  h os pit al-a p pr o v e d  cl e a ni n g  pr oc e d ur e.  All i nf us i o n  s et  
7 4 4  
e q ui p m e nt will b e si n gl e p ati e nt us e o nl y (i nf usi o n s et i ns erti o n kits, t u bi n g, c artri d g es etc.)   
7 4 5  
T h e st u d y bl o o d gl uc os e m et er a n d bl o o d k et o n e m et er ar e l a b el e d f or si n gl e -p ati e nt us e. 
7 4 6  
D uri n g  t h e st u d y, t h es e d e vic es m a y b e r e us e d aft er cl e a ni n g a d h eri n g t o a h os pit al -a p pr o v e d 
7 4 7  
cl e a ni n g pr oc e d ur e.  
7 4 8  
 D e vic e Cl e a ni n g I nstr ucti o ns  
7 4 9  
C G M cl e a ni n g i nstr ucti o ns ar e pr o vi d e d i n t h e D exc o m G 4 PL A TI N U M ( Pr of essi o n al) Cl e a ni n g a n d 
7 5 0  
Disi nf ecti o n m a n u al (c urr e nt e diti o n). T h e tr a ns mitt er s h o ul d b e cl e a n e d wit h Cl or ox H e alt hc ar e ® 
7 5 1  
Bl e ac h G er mici d al Cl e a n er or a n y disi nf ect a nt pr o d uct i n a s pr a y b ottl e c o nt ai ni n g a bl e ac h 
7 5 2  
s ol uti o n of 6 5 0 0 p arts p er milli o n wit h t h e E P A r e gistr ati o n n u m b er 5 6 3 9 2- 7. T h e tr a ns mitt er will 
7 5 3  
b e s u b m er g e d i n t his s ol uti o n a n d t h e n pl ac e d o n a n a bs or b e nt wi p e or cl e a n s urf ac e . T w o s pr a ys 
7 5 4  
will b e dis p e ns e d fr o m t h e Cl or ox cl e a n er o nt o e ac h si d e of t h e tr a ns mitt er. A n yl o n br us h will 
7 5 5  
b e us e d t o scr u b t h e tr a ns mitt er o n all si d es f or 3 0 s ec o n ds . T h e tr a ns mitt er will b e pl ac e d i n t h e 
7 5 6  
Cl or ox Cl e a n er s ol uti o n f or o n e mi n ut e. Tr a ns mitt er is t h e n ri ns e d u n d er fl o wi n g t a p w at er f or 
7 5 7  
t e n s ec o n ds. T h e tr a ns mitt er will t h e n b e disi nf ect e d usi n g a disi nf ect a nt pr o d uct wit h E P A 
7 5 8  
r e gistr ati o n n u m b er 5 6 3 9 2-7 usi n g si mil ar pr oc e d ur es as t h e cl e a ni n g pr oc ess .  
7 5 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 5  of 6 6  
 
P er t h e p u m p m a n uf act ur er, t h e i ns uli n p u m p will b e cl e a n e d wit h a d a m p li nt-fr e e cl ot h. Us e of 
7 6 0  
h o us e h ol d or i n d ustri al cl e a n ers, s ol v e nts, bl e ac h, sc o uri n g p a ds, c h e mi c als, or s h ar p i nstr u m e nts 
7 6 1  
ar e pr o hi bit e d. T h e p u m p s h o ul d n e v er b e s u b m er g e d i n w at er. I f n e e d e d, us e o nly a v er y mil d 
7 6 2  
d et er g e nt, s uc h as a bit of li q ui d s o a p wit h w ar m w at er. A s oft t o w el will b e us e d t o dr y t h e p u m p.  
7 6 3  
T h e gl uc o m et er is cl e a n e d a n d disi nf ect e d wit h t w o s e p ar at e S u p er S a ni -Cl ot hs ( E P A n u m b er 
7 6 4  
9 4 8 0 -4). T h e e ntir e s urf ac e will b e cl e a n e d, m a ki n g s ur e t h e s urf ac e st a ys w et f or 2 mi n ut es. T his 
7 6 5  
st e p is r e p e at e d wit h a cl e a n cl ot h f or disi nf ecti n g t h e d e vic e.  
7 6 6  
T h e Pr ecisi o n Xtr a Us er’s G ui d e s u g g ests t h at h e alt hc ar e pr of essi o n als us e 1 0 % bl e ac h, 7 0 % 
7 6 7  
alc o h ol or 1 0 % a m m o ni a t o cl e a n t h e d e vic e.  
7 6 8  
E q ui p m e nt t h at t o uc h es i nt act s ki n will b e cl e a n e d wit h et h yl or is o pr o p yl alc o h ol ( 7 0 -9 0 %), 
7 6 9  
q u at er n ar y a m m o ni u m g er mici d al d et er g e nt (i. e. , C a vici d e, E P A n u m b er 4 6 7 8 1) or h o us e h ol d 
7 7 0  
bl e ac h. T h e c o nt act ti m e o n t h e s urf ac e d e p e n ds o n t h e m et h o d us e d t o cl e a n t h e e q ui p m e nt. 
7 7 1  
C a vici d e r e q uir es t hr e e mi n ut es o n t h e s urf ac e of t h e e q ui p m e nt. Cl or ox G er mici d al Bl e ac h Wi p es 
7 7 2  
r e q uir e t w o mi n ut es o n t h e e q ui p m e nt. T h e s urf ac e s h o ul d r e m ai n w et (i. e., sli g htly d a m p) wit h 
7 7 3  
t h e disi nf ect a nt t o b e c o nsi d er e d eff ecti v e t h o u g h n ot w et e n o u g h t o l e a v e dr o ps of li q ui d.  
7 7 4  
I n t h e e v e nt a m a n uf act ur er u p d at es t h eir cl e a ni n g pr oc e d ur es, t h e st u d y t e a m will a d h er e t o t h e 
7 7 5  
m ost c urr e nt r ec o m m e n d ati o ns.  
7 7 6  
T h er e is t h e r is k of bl o o d s a m pli n g c oll ecti o n a n d c o nt a mi n ati o n fr o m s a m pli n g t ec h ni q u es. H a n d 
7 7 7  
w as hi n g wit h eit h er s o a p & w at er or w at erl ess h a n d s a nitiz er will b e us e d pri or t o c ari n g f or t h e 
7 7 8  
st u d y p artici p a nt . Gl o v es will b e w or n d uri n g bl o o d s a m pl e c oll ecti o n a n d pr oc essi n g. M e dic al 
7 7 9  
p ers o n n el will c o nti n u e t o pr actic e h y gi e n e f or t h e p artici p a nt ’s pr ot ecti o n (i. e., h a n d w as hi n g, 
7 8 0  
c h a n gi n g gl o v es fr e q u e ntl y, dis p osi n g n e e dl es pr o p erl y). Gl o v es will b e r e m o v e d , a n d h a n ds 
7 8 1  
w as h e d  or s a nitiz e d  pri or t o l e a vi n g a n d u p o n r et ur n t o t h e p artici p a nt ’s r o o m. S oil e d li n e n will 
7 8 2  
b e c h a n g e d t o mi ni miz e t h e tr a nsf er of p at h o g e nic or g a nis ms.  
7 8 3  
 H b 1 Ac Ris k  
7 8 4  
A n N GS P P oi nt of C ar e a n al yz er (i. e. , D C A V a nt a g e A n al yz er) will b e utiliz e d at t h e r es e arc h sit e 
7 8 5  
t o o bt ai n t h e p artici p a nt ’s H b A 1c l e vel.  
7 8 6  
 Ot h er Ris ks  
7 8 7  
S o m e p artici p a nts m a y d e v el o p s ki n irrit ati o n or all er gic r e acti o ns t o t h e a d h esi v es us e d t o s ec ur e 
7 8 8  
t h e C G M, or t o s ec ur e t h e i ns uli n i nf usi o n s ets f or t h e c o nti n u o us s u bc ut a n e o us i ns uli n i nf usi o n. 
7 8 9  
If t h es e r e acti o ns occ ur, diff er e nt a d h esi v es or “ u n d er-t a pi n g” (s uc h as wit h I V 3 0 0 0, T e g a d er m, 
7 9 0  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 6  of 6 6  
 
etc.) will b e tri e d, sit es will b e r ot at e d fr e q u e ntl y, a n d a mil d t o pic al st er oi d cr e a m or ot h er 
7 9 1  
m e dic ati o n m a y b e r e q uir e d.  
7 9 2  
W h e n e v er t h e s ki n is br o k e n t h er e is t h e p ossi bility of a n i nf ecti o n . T h e C G M a n d p u m p i nf usi o n 
7 9 3  
sit es ar e i ns ert e d u n d er t h e s ki n. It is p ossi bl e t h at a n y p art t h at is i ns ert e d u n d er t h e s ki n m a y 
7 9 4  
c a us e a n i nf ecti o n. T h es e occ ur v er y i nfr e q u e ntl y, b ut, if a n i nf ecti o n w as t o occ ur, or al a n d/ or 
7 9 5  
t o pic al a nti bi otics c a n b e us e d. T h e ris k of s ki n pr o bl e ms c o ul d b e gr e at er if y o u us e a s e ns or f or 
7 9 6  
l o n g er t h a n it is s u p p os e d t o b e us e d. T h er ef or e, p artici p a nts will b e c ar ef ull y i nstr uct e d a b o ut 
7 9 7  
pr o p er us e of t h e s e ns or.  
7 9 8  
D at a d o w nl o a d e d fr o m t h e C G M, i ns uli n p u m p, a n d gl uc os e a n d k et o n e m e t er will b e c oll ect e d 
7 9 9  
f or  t h e  st u d y  as  m e as ur es  of  di a b et es  s elf-m a n a g e m e nt  b e h a vi ors . S o m e  p e o pl e  
8 0 0  
m a y  b e  u nc o mf ort a bl e wit h t h e r es e arc h ers' h a vi n g s uc h d et ail e d i nf or m ati o n a b o ut t h eir d ail y 
8 0 1  
di a b et es h a bits.  
8 0 2  
 K n o w n P ot e nti al B e n efits  
8 0 3  
It  is  ex p ect e d  t h at  t his  pr ot oc ol  will  yi el d  i ncr e as e d  k n o wl e d g e  a b o ut  usi n g  a n  a d v a nc e d 
8 0 4  
a ut o m at e d cl os e d -l o o p s yst e m wit h a d v a nc e d acti o n t o c o ntr ol gl uc os e l e v els  b as e d o n S I. T h e 
8 0 5  
i n di vi d u al p artici p a nt m a y n ot b e n efit fr o m st u d y p artici p ati o n. 
8 0 6  
 Ris k Ass ess m e nt  
8 0 7  
B as e d o n t h e f acts t h at ( 1) a d ults a n d a d ol esc e nts wit h di a b et es ex p eri e nc e mil d h y p o gl yc e mi a 
8 0 8  
a n d h y p er gl yc e mi a fr e q u e ntl y as a c o ns e q u e nc e of t h e dis e as e a n d its m a n a g e m e nt, ( 2) t h e st u d y 
8 0 9  
i nt er v e nti o n i n v ol v es p eri o dic a ut o m at e d i ns uli n d osi n g t h at m a y i ncr e as e t he li k eli h o o d of 
8 1 0  
h y p o gl yc e mi a, a n d p eri o dic a ut o m at e d att e n u ati o n of i ns uli n d eli v er y t h at m a y i ncr e as e t h e 
8 1 1  
li k eli h o o d of h y p er gl yc e mi a, ( 3) miti g ati o ns ar e i n pl ac e, a n d h a v e b e e n t est e d i n pri or st u di es 
8 1 2  
usi n g t h e i n v esti g ati o n al d e vic e s yst e m i n t h e h o m e s etti n g, t h at li mit t h e li k eli h o o d of exc essi v e 
8 1 3  
i ns uli n d osi n g or pr ol o n g e d wit h dr a w al of i ns uli n, a n d ( 4) r a pi d r e v ers al of h y p o gl yc e mi a a n d 
8 1 4  
h y p er gl yc e mi a c a n b e ac hi e v e d, it is t h e ass ess m e nt of t h e i n v esti g at ors t h at t his pr ot oc ol f alls 
8 1 5  
u n d er D H H S 4 6. 4 0 5 w hic h is a mi n or i ncr e as e o v er mi ni m al ris k. I n a d diti o n, it is t h e b eli ef of t h e 
8 1 6  
i n v esti g at ors t h at t his st u d y als o pr es e nts pr os p ect of dir ect b e n efit t o t h e p artici p a nts a n d 
8 1 7  
g e n er al b e n efit t o ot h ers wit h di a b et es.  
8 1 8  
 
8 1 9  
T h e st u d y is b ei n g c o n d uct e d i n c o m pli a nc e wit h t h e p olici es d escri b e d i n t h e st u d y p olici es 
8 2 0  
d oc u m e nt, wit h t h e et hic al pri nci pl es t h at h a v e t h eir ori gi n i n t h e D ecl ar ati o n of H elsi n ki, wit h 
8 2 1  
t h e pr ot oc ol d escri b e d h er ei n, a n d wit h t h e st a n d ar ds of G o o d Cli nic al Pr actic e ( G C P). 
8 2 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 7  of 6 6  
 
W h e n e v er p ossi bl e, d at a will b e dir ectl y c oll ect e d i n el ectr o nic c as e r e p ort f or ms, w hic h will b e 
8 2 3  
c o nsi d er e d t h e s o urc e d at a. 
8 2 4  
T h e pr ot oc ol is c o nsi d er e d a si g nific a nt ris k d e vic e st u d y, d u e t o t h e f act t h at t h e cl os e d l o o p 
8 2 5  
s yst e m is ex p eri m e nt al. T h er ef or e, a n i n v esti g ati o n al d e vic e ex e m pti o n (I D E) fr o m t h e U. S. F o o d 
8 2 6  
a n d Dr u g A d mi nistr ati o n (F D A) is r e q uir e d t o c o n d uct t h e st u d y.  
8 2 7  
 
8 2 8  
T h e st u d y i ncl usi o n/ excl usi o n crit eri a h a v e b e e n o utli n e d t o i ncl u d e o nl y f ull y -v acci n at e d st u d y 
8 2 9  
p artici p a nts. T h e pr es e nc e of o nl y v acci n at e d p artici p a nts r e pr es e nt s t h e m ai n a p pr o ac h t o 
8 3 0  
C O VI D -1 9 ris k miti g ati o n. F urt h er, all st u d y /c a m p st aff m e m b ers will b e f ull y v acci n at e d as w ell 
8 3 1  
w h e n  t h e c a m p is sc h e d ul e d t o t a k e pl ac e. 
8 3 2  
A d diti o n al l a y er s t o C O VI D-1 9 ris k miti g ati o n will als o b e i m pl e m e nt e d : 
8 3 3  
  B ef or e a d missi o n (s), all p artici p a nts a n d st aff will t a k e a C O VI D P C R t est; a n e g ati v e r es ult 
8 3 4  
is n e e d e d t o b e p art of t h e st u d y: 
8 3 5  
• 
if a n y C O VI D s y m pt o ms d e v el o p aft er t a ki n g t h e t est, t h e p ers o n will n ot b e 
8 3 6  
all o w e d at c a m p;  
8 3 7  
• 
if a n y c o nt act wit h a C O VI D p ositi v e p ers o n h a p p e ns i n t h e 7 d a ys pri or t o c a m p, 
8 3 8  
t h e p ers o n will n ot b e all o w e d at c a m p; 
8 3 9  
• 
if t h e p ers o n h a d a p ositi v e C O VI D t est r es ult i n t h e 1 0  d a ys pri or t o c a m p, t h e 
8 4 0  
p ers o n will n ot b e all o w e d at c a m p . 
8 4 1  
  D uri n g c a m p  a d missi o n (s), p artici p a nts will b e gr o u p e d i n s m all p o ds ( 5-6 p artici p a nts 
8 4 2  
e ac h) f or t h e d ail y acti viti es; c o u ns el ors will b e assi g n e d t o a p o d a n d m ai nt ai n e d f or t h e 
8 4 3  
e ntir e c a m p d ur ati o n  w h e n p ossi bl e . 
8 4 4  
  D uri n g c a m p a d missi o n (s), t h e m aj ority of t h e acti viti es will t a k e pl ac e o ut d o or, a n d all 
8 4 5  
eff orts will b e m a d e t o e ns ur e p h ysic al dist a nci n g b et w e e n m e m b ers of diff er e nt p o ds 
8 4 6  
d uri n g t h e acti viti es . 
8 4 7  
  D uri n g  c a m p  a d missi o n (s), p artici p a nts  will  b e  sl e e pi n g  i n  c a bi ns  acc or di n g  t o  t h e  
8 4 8  
c orr es p o n di n g p o d; c o u ns el ors will b e sl e e pi n g wit h t h e assi g n e d p o d f or t h e e ntir e c a m p 
8 4 9  
d ur ati o n ; diff er e nt p o ds will b e assi g n e d t o diff er e nt c a bi ns wit h n o i n d o or c o m m o n p arts. 
8 5 0  
  M e als will b e c o ns u m e d o ut d o or w h e n p ossi bl e.  
8 5 1  
  S oci al dist a nci n g b et w e e n p e o pl e n ot b el o n gi n g t o t h e s a m e p o d will b e m ai nt ai n e d w h e n 
8 5 2  
p ossi bl e.  
8 5 3  
  O ut d o or m as ki n g p olicy: n o m as ki n g will b e m a n d at e d; exc e pti o n: if t w o p e o pl e t h at d o 
8 5 4  
n ot b el o n g t o t h e s a m e p o d n e e d t o b e l ess t h a n 6ft a p art f or m or e t h a n 5 c o ns ec uti v e 
8 5 5  
mi n ut es, m as ki n g will b e r e q uir e d f or b ot h p e o pl e.  
8 5 6  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 8  of 6 6  
 
  I n d o or m as ki n g p olicy: u ni v ers al m as ki n g will b e m a n d at e d; exc e pti o n: w hil e e ati n g, 
8 5 7  
dri n ki n g, s h o w eri n g, a n d sl e e pi n g; d uri n g t h es e ti m es, p h ysic al dist a nci n g will b e e nf orc e d 
8 5 8  
b et w e e n p e o pl e n ot b el o n gi n g t o t h e s a m e p o d.  
8 5 9  
  If a p ers o n d e v el o ps C O VI D s y m pt o ms d uri n g c a m p, t h e p ers o n will b e disc h ar g e d fr o m 
8 6 0  
t h e st u d y. B ef or e l e a vi n g c a m p sit e, t h e p ers o n will b e t est e d f or C O VI D usi n g a n a nti g e nic 
8 6 1  
r a pi d t est t h at will b e a v ail a bl e o n sit e.  
8 6 2  
  If a p ers o n  wit hi n a p o d ( p artici p a nt or c o u ns el or)  t ests p ositi v e, u ni v ers al m as ki n g f or t h e 
8 6 3  
p o d  m e m b ers  will b e m a n d at e d i n d o or a n d o ut d o or, wit h t h e exc e pti o n of  e ati n g, 
8 6 4  
dri n ki n g, s h o w eri n g, a n d sl e e pi n g; t h es e acti viti es will t a k e pl ac e s e p ar at el y fr o m ot h er 
8 6 5  
p o ds.  
8 6 6  
  H a n d s a nitiz ers will b e a v ail a bl e d uri n g t h e e ntir e st u d y d ur ati o n a n d st u d y p artici p a nts 
8 6 7  
a n d st aff will b e e nc o ur a g e d t o fr e q u e ntl y s a nitiz e t h eir h a n d s. 
8 6 8  
  If t h e C O VI D-r el at e d sit u ati o n c h a n g es b ef or e t h e c a m p a d missi o n, t h e st u d y t e a m will r e -
8 6 9  
e v al u at e t h es e g ui d eli n es i n a gr e e m e nt wit h C D C r ec o m m e n d ati o ns, a n d t his pr ot oc ol 
8 7 0  
m a y b e c h a n g e d if n e e d e d.  
8 7 1  
 P art ici p a nts a n d St u d y P ers o n n el 
8 7 2  
T h e f oll o wi n g g ui d eli n es will b e f oll o w e d d uri n g e ac h c a m p a d missi o n:  
8 7 3  
•  All p artici p a nts will b e i n eli gi bl e if t h e y h av e h a d k n o w n C O VI D -1 9  ex p os ur es i n t h e 7 d a ys 
8 7 4  
pri or t o a n y a d missi o n(s) .  
8 7 5  
•  All p artici p a nts will b e i n eli gi bl e if t h e y h a v e h a d a p ositi v e C O VI D t est r es ults i n t h e 1 0 
8 7 6  
d a ys pri or t o a n y a d missi o n(s).  
8 7 7  
•  All p artici p a nts will b e i n eli gi bl e if t h e y d e v el o p  s y m pt o ms of C O VI D -1 9 aft er t a ki n g t h e 
8 7 8  
pr e -a d missi o n m a n d at or y C O VI D P C R t est .  
8 7 9  
•  N o n -v acci n at e d p artici p a nts will n ot b e eli gi bl e f or t h e st u d y .  
8 8 0  
•  P artici p a nts will sl e e p i n  c a bi ns wit h m e m b ers of t h e s a m e p o d;  all m e als will b e e at e n 
8 8 1  
o ut d o or a n d pr o vi d e d i n i n di vi d u al pr e -p ack a g e d b ox e s.  
8 8 2  
•  P artici p a nts  will  b e  assi g n e d  t o  s m all  gr o u ps  ( p o ds),  w hic h  will  r e m ai n  c o nsist e nt  
8 8 3  
t hr o u g h o ut t h e st u d y a d missi o n(s)  f or all acti viti es. T h e st u d y t e a m will ai m t o li mit 
8 8 4  
c h a n g es i n st affi n g a m o n g t h e p o ds.  
8 8 5  
D e v el o p m e nt of C O VI D -1 9 s y m pt o ms d uri n g st u d y a d missi o n(s)  is d et ail e d i n S ecti o n 1 1. 4 . 
8 8 6  
 E n vir o n m e nt  
8 8 7  
T h e st aff at C a m p H oli d a y Tr ails wi ll w or k t o r e d uc e t h e ris k of C O VI D-1 9  ex p os ur e b y f oll o wi n g 
8 8 8  
t h e g ui d eli n es i n dic at e d i n t his pr ot oc ol. 
8 8 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 4 9  of 6 6  
 
 Acti viti es  
8 9 0  
Gr o u p acti viti es ar e a n i m p ort a nt p art of a c a m p ex p eri e nc e a n d will b e d o n e wit h t h e f oll o wi n g 
8 9 1  
pr ec a uti o ns i n pl ac e:  
8 9 2  
•  All acti viti es will b e d o n e o ut d o or s 
8 9 3  
•  P artici p a nt s will b e assi g n e d t o s m all gr o u ps or p o ds t o li mit ex p os ur es 
8 9 4  
•  St aff will b e m ai nt ai n e d f or t h e s a m e p o d as m uc h as p ossi bl e d uri n g e ac h a d missi o n  
8 9 5  
•  N o hi g h -ris k acti viti es r e q uiri n g s ust ai n e d cl os e c o nt act will b e i ncl u d e d a n d a n y hi g h er 
8 9 6  
ris k c o nt act-s p ort will b e i ncl u d e d i n a s kill b uil di n g f or m at s o as t o all o w f or a d e q u at e 
8 9 7  
p h ysic al dist a nci n g a n d a v oi d u n n ec ess ary ris k t o st u d y p artici p a nts     
 
8 9 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 0  of 6 6  
 
C h a pt er 1 1:    A d v ers e E v e nts, D e vic e Iss u es, a n d St o p pi n g R ul es  
8 9 9  
 
9 0 0  
 A d v ers e E v e nts ( A E)  
9 0 1  
A n y u nt o w ar d m e dic al occ urr e nc e i n a st u d y p artici p a nt, irr es p ecti v e of t h e r el ati o ns hi p b et w e e n 
9 0 2  
t h e a d v ers e e v e nt a n d t h e d e vic e(s) u n d er i n v esti g ati o n (s ecti o n 1 1. 2 ) f or r e p ort a bl e a d v ers e 
9 0 3  
e v e nts f or t his pr ot oc ol).  
9 0 4  
 S eri o us  A d v ers e E v e nt ( S A E)  
9 0 5  
 A n y u nt o w ar d m e dic al occ urr e nc e t h at:  
9 0 6  
•  R es ults i n d e at h.  
9 0 7  
•  Is lif e-t hr e at e ni n g; ( a n o n -lif e-t hr e at e ni n g e v e nt w hic h, h a d it b e e n m or e s e v er e, 
9 0 8  
mi g ht h a v e b ec o m e lif e -t hr e at e ni n g, is n ot n ec ess aril y c o nsi d er e d a s eri o us a d v ers e 
9 0 9  
e v e nt).  
9 1 0  
•  R e q uir es i n p ati e nt h os pit aliz ati o n or pr ol o n g ati o n of existi n g h os pit aliz ati o n.  
9 1 1  
•  R es ults i n p ersist e nt or si g ni fic a nt dis a bility/i nc a p acity or s u bst a nti al disr u pti o n of t h e 
9 1 2  
a bilit y t o c o n d uct n or m al lif e f u ncti o ns ( lif e t hr e at e ni n g). 
9 1 3  
•  Is a c o n g e nit al a n o m al y or birt h d ef ect. 
9 1 4  
•  Is  c o nsi d er e d  a  si g nific a nt  m e dic al  e v e nt  b y  t h e  i n v esti g at or  b as e d  o n  m e dic al  
9 1 5  
j u d g m e nt  ( e. g.,  m a y  j e o p ar diz e  t h e  p artici p a nt  or  m a y  r e q uir e  m e dic al/s ur gic al  
9 1 6  
i nt er v e nti o n t o pr e v e nt o n e of t h e o utc o m es list e d a b o v e). 
9 1 7  
 U n a ntici p at e d A d v ers e D e vic e Eff ect ( U A D E)  
9 1 8  
A n y s eri o us a d v ers e eff ect o n h e alt h or s af ety or a n y lif e -t hr e at e ni n g pr o bl e m or d e at h c a us e d 
9 1 9  
b y, or ass oci at e d wit h, a d e vic e, if t h at eff ect, pr o bl e m, or d e at h w as n ot pr e vi o usl y i d e ntifi e d i n 
9 2 0  
n at ur e, s e v erit y, or d e gr e e of i nci d e nc e i n t h e i n v esti g ati o n al pl a n or a p plic ati o n (i ncl u di n g a 
9 2 1  
s u p pl e m e nt ar y pl a n or a p plic ati o n), or a ny ot h er u na ntici p at e d s eri o us pr o bl e m ass oci at e d wit h 
9 2 2  
a d e vic e t h at r el at es t o t h e ri g hts, s af ety, or w elf ar e of p artici p a nts ( 2 1 C F R 8 1 2. 3(s)).  
9 2 3  
 A d v ers e D e vic e Eff ect ( A D E)  
9 2 4  
A n y u nt o w ar d m e dic al occ urr e nc e i n a st u d y p artici p a nt w hic h t h e d e vic e m a y h a v e c a us e d or t o  
9 2 5  
w hic h t h e d e vic e m a y h a v e c o ntri b ut e d . 
9 2 6  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 1  of 6 6  
 
 D e vic e C o m pl ai nts a n d M alf u ncti o ns  
9 2 7  
A d e vic e c o m plic ati o n or c o m pl ai nt is s o m et hi n g t h at h a p p e ns t o a d e vic e or r el at e d t o d e vic e 
9 2 8  
p erf or m a nc e, w h er e as a n a d v ers e e v e nt h a p p e ns t o a p artici p a nt . A d e vic e c o m pl ai nt m a y occ ur 
9 2 9  
i n d e p e n d e ntl y fr o m a n A E, or al o n g wit h a n A E. A n  A E m a y occ ur wit h o ut a d e vic e c o m pl ai nt or 
9 3 0  
t h er e m a y b e a n A E r el at e d t o a d e vic e c o m pl ai nt. A d e vic e m alf u ncti o n is a n y f ail ur e of a d e vic e 
9 3 1  
t o  m e et  its  p erf or m a nc e  s p ecific ati o ns  or  ot h er wis e  p erf or m  as  i nt e n d e d . P erf or m a nc e 
9 3 2  
s p ecific ati o ns i ncl u d e all cl ai ms m a d e i n t h e l a b eli n g f or t h e d e vic e. T h e i nt e n d e d p erf or m a nc e 
9 3 3  
of a d e vic e r ef ers t o t h e i nt e n d e d us e f or w hic h t h e d e vic e is l a b el e d or m ar k et e d. ( 2 1 C F R 8 0 3. 3) .  
9 3 4  
 
9 3 5  
F or t his pr ot oc ol, a r e p ort a bl e a d v ers e ev e nt i ncl u d es a n y u nt o w ar d m e dic al occ urr e nc e t h at 
9 3 6  
m e ets o n e of t h e f oll o wi n g crit eri a:  
9 3 7  
•  A s eri o us a d v ers e e v e nt  as d efi n e d i n s ecti o n 1 1. 1. 2  
9 3 8  
•  A n A d v ers e D e vic e Eff ect as d efi n e d i n s ecti o n 1 1. 1. 4 , u nl ess excl u d e d fr o m r e p orti n g 
9 3 9  
i n s ecti o n 1 1. 8  
9 4 0  
•  A n A d v ers e Ev e nt as d efi n e d i n s ecti o n 1 1. 1. 4  occ urri n g i n ass oci ati o n wit h a st u dy 
9 4 1  
pr oc e d ur e  
9 4 2  
•  A n A E as d efi n e d i n s ecti o n 1 1. 1. 1  w hic h l e a ds t o disc o nti n u ati o n of a st u d y d e vic e f or 
9 4 3  
2 or m or e h o u rs 
9 4 4  
•  Hy p o gl yc e mi a m e eti n g t h e d efi niti o n of s e v er e h y p o gl yc e mi a as d efi n e d i n s ecti o n 
9 4 5  
1 1. 2. 1   
9 4 6  
•  Di a b etic k et o aci d osis ( D K A) as d efi n e d i n s ecti o n 1 1. 2. 2  or i n t h e a bs e nc e of D K A, a 
9 4 7  
h y p er gl yc e mic or k et osis e v e nt m e eti n g t h e crit eri a d efi n e d b el o w  
9 4 8  
Hy p o gl yc e mi a a n d h y p er gl yc e mi a n ot m e eti n g t h e crit eri a b el o w will n ot b e r ec or d e d as a d v ers e 
9 4 9  
e v e nts u nl ess ass oci at e d wit h a n A d v ers e D e vic e Eff ect . S ki n r e acti o ns fr o m s e ns or pl ac e m e nt 
9 5 0  
ar e o nl y r e p ort a bl e if s e v er e a n d/ or r e q uir e d tr e at m e nt.  
9 5 1  
 H y p o gl yc e mi a E v e nt  
9 5 2  
Hy p o gl yc e mi a n ot ass oci at e d wit h a n A d v ers e D e vic e Eff ect is o nl y r e p ort a bl e as a n a d v ers e e v e nt 
9 5 3  
w h e n t h e f oll o wi n g d efi niti o n f or s e v er e hy p o gl yc e mi a is m et:   
9 5 4  
•  th e e v e nt r e q uir e d assist a nc e of a n ot h er p ers o n d u e t o alt er e d c o nsci o us n ess, a n d 
9 5 5  
r e q uir e d a n ot h er p ers o n t o acti v el y a d mi nist er c ar b o h y dr at e, gl uc ag o n, or ot h er 
9 5 6  
r es uscit ati v e acti o ns;  
9 5 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 2  of 6 6  
 
•  im p air e d c o g niti v el y t o t h e p oi nt t h at h e/s h e w as u n a bl e t o tr e at hi ms elf/ h ers elf, w as 
9 5 8  
u n a bl e t o v er b aliz e his/ h er n e e ds, w as i nc o h er e nt, dis ori e nt e d, a n d/ or c o m b ati v e, or 
9 5 9  
ex p eri e nc e d  s eiz ur e  or  c o m a . T h es e e pis o d es  m a y  b e  ass oci at e d  wit h  s uffici e nt  
9 6 0  
n e ur o gl yc o p e ni a t o i n d uc e s eiz ur e or c o m a;  
9 6 1  
•  if pl as m a gl uc os e m e as ur e m e nts ar e n ot a v ail a bl e d uri n g s uc h a n e v e nt, n e ur ol o gic al 
9 6 2  
r ec o v er y attri b ut a bl e t o t h e r est or ati o n of pl as m a gl uc os e t o n or m al is c o nsi d er e d 
9 6 3  
s uffici e nt e vi d e nc e t h at t h e e v e nt w as i n d uc e d b y a l o w pl as m a gl uc os e c o nc e ntr ati o n. 
9 6 4  
 H y p er gl yc e mi a E v e nts/ Di a b et es K et o aci d osis  
9 6 5  
Hy p er gl yc e mi a n ot ass oci at e d wit h a n A d v ers e D e vic e Eff ect is o nl y r e p ort a bl e as a n a d v ers e 
9 6 6  
e v e nt w h e n o n e of t h e f o ll o wi n g f o ur crit eri a is m et:  
9 6 7  
•  t h e e v e nt i n v ol v e d D K A, as d efi n e d b y t h e Di a b et es C o ntr ol a n d C o m plic ati o ns Tri al 
9 6 8  
( D C C T) a n d d escri b e d b el o w 
9 6 9  
•  e v al u ati o n or tr e at m e nt w as o bt ai n e d at a h e alt h c ar e pr o vi d er f acility f or a n ac ut e 
9 7 0  
e v e nt i n v ol vi n g h y p er gl yc e mi a or k et osis  
9 7 1  
•  bl o o d  k et o n e  l e v el  ≥1. 5  m m ol/L  a n d  c o m m u nic ati o n  occ urr e d  wit h  a  h e alt h  c ar e 
9 7 2  
pr o vi d er at t h e ti m e of t h e e v e nt  
9 7 3  
•  bl o o d k et o n e l e v el ≥3. 0 m m ol/L, e v e n if t h er e w as n o c o m m u nic ati o n wit h a h e alt h 
9 7 4  
c ar e pr o vi d er 
9 7 5  
Hy p er gl yc e mic e v e nts ar e cl assifi e d as D K A if t h e f oll o wi n g ar e pr es e nt:  
9 7 6  
•  S y m pt o ms s uc h as p ol y uri a, p ol y di psi a, n a us e a, or v o miti n g;  
9 7 7  
•  S er u m k et o n es ≥1. 5 m m ol/L or l ar g e/ m o d er at e ur i n e k et o n es; 
9 7 8  
•  Tr e at m e nt pr o vi d e d i n a h e alt h c ar e f acility  
9 7 9  
All r e p ort a bl e A d v ers e Ev e nts — w h et h er v ol u nt e er e d b y t h e p artici p a nt, disc o v er e d b y st u d y 
9 8 0  
p ers o n n el d uri n g q u esti o ni n g, or d et ect e d t hr o u g h p h ysic al ex a mi n ati o n, l a b or at or y t est, or 
9 8 1  
ot h er m e a ns — will b e r e p ort e d o n a n a dv ers e e v e nt f or m o nli n e . E ac h a d v ers e ev e nt f or m is 
9 8 2  
r e vi e w e d b y t h e M e dic al M o nit or t o v erify th e c o di n g a n d t h e r e p orti n g t h at is r e q uir e d.  
9 8 3  
 
9 8 4  
T h e st u d y i n v esti g at or will ass ess t h e r el ati o ns hi p of a n y a d v ers e e v e nt t o b e r el at e d or u nr el at e d 
9 8 5  
b y d et er mi ni n g if t h er e is a r e as o n a bl e p ossi bility t h at t h e a d v ers e e v e nt m a y h a v e b e e n c a us e d 
9 8 6  
b y t h e st u d y d e vic e.  
9 8 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 3  of 6 6  
 
T o e ns ur e c o nsist e ncy of a d v ers e e v e nt c a us ality ass ess m e nts, i n v esti g at ors s h o ul d a p pl y t h e 
9 8 8  
f oll o wi n g g e n er al g ui d eli n e w h e n d et er mi ni n g w h et h er a n a d v ers e e v e nt is r el at e d: 
9 8 9  
•  T h er e is a pl a usi bl e t e m p or al r el ati o ns hi p b et w e e n t h e o ns et of t h e a d v ers e e v e nt a n d 
9 9 0  
t h e st u d y i nt er v e nti o n, a n d t h e a d v ers e e v e nt c a n n ot b e r e a dil y ex pl ai n e d b y t h e 
9 9 1  
p artici p a nt’s cli nic al st at e, i nt erc urr e nt ill n ess, or c o nc o mit a nt t h er a pi es; a n d/ or t h e 
9 9 2  
a d v ers e e v e nt f oll o ws a k n o w n p att er n of r es p o ns e t o t h e st u d y i nt er v e nti o n; a n d/ or 
9 9 3  
t h e a d v ers e e v e nt a b at es or r es ol v es u p o n disc o nti n u ati o n of t h e st u d y i nt er v e nti o n 
9 9 4  
or d os e r e d ucti o n a n d, if a p plic a bl e, r e a p p e ars u p o n r e -c h all e n g e. 
9 9 5  
•  Evi d e nc e  exists  t h at  t h e  a d v ers e  e v e nt  h as  a n  et i ol o gy  ot h er  t h a n  t h e  st u d y  
9 9 6  
i nt er v e nti o n ( e. g., pr e existi n g m e dic al c o n diti o n, u n d erl yi n g dis e as e, i nt erc urr e nt 
9 9 7  
ill n ess,  or  c o nc o mit a nt  m e dic ati o n);  a n d/ or  t h e  a d v ers e  e v e nt  h as  n o  pl a usi bl e  
9 9 8  
t e m p or al r el ati o ns hi p t o st u d y i nt er v e nti o n. 
9 9 9  
 
1 0 0 0  
W hil e w e ar e t a ki n g si g nific a nt st e ps t o pr e v e nt tr a ns missi o n of C O VI D -1 9 d uri n g t his st u d y, t h er e 
1 0 0 1  
is a p ossi bilit y t h at p artici p a nts ar e i nf ect e d wit h C O VI D-1 9. T h e pr o b a bility t h at i nf ecti o n is 
1 0 0 2  
r el at e d t o t h e st u d y m a y b e i nf err ed i n p art b y t h e ti mi n g, wit h s y m pt o ms b e gi n ni n g o n d a y s 1-
1 0 0 3  
2 ,  or d a y s 5-6 i n a t w o w e e k e n d c a m p a d missi o n, of t h e st u d y b ei n g m or e li k el y n ot r el at e d a n d 
1 0 0 4  
o ns et of s y m pt o ms aft er w ar d b ei n g p ossi bl y r el at e d t o ex p os ur e d uri n g t h e st u d y.  
1 0 0 5  
•  P artici p a nts or st u d y st aff w h o d e v el o p C O VI D -1 9 s y m pt o ms  ( e. g., f e v er, c o u g h, 
1 0 0 6  
s h ort n ess  of  br e at h  ( n ot  r el at e d  t o  c a m p  acti viti es))  d uri n g  t h e  st u d y  will  b e  
1 0 0 7  
i m m e di at el y is ol at e d a n d disc h ar g e d fr o m t h e st u d y. B ef or e disc h ar g e, p artici p a nts 
1 0 0 8  
us e of a f aci al m as ks will b e m a n d at e d. P artici p a nts will n ot e n g a g e i n f urt h er c a m p 
1 0 0 9  
acti viti es pri or t o disc h ar g e. At disc h ar g e, p artici p a nts will b e a d vis e d o n a p pr o pri at e 
1 0 1 0  
is ol ati o n a n d t esti n g t o b e c o m pl et e d.  
1 0 1 1  
•  B ef or e disc h ar g e, s y m pt o m atic p artici p a nts will b e t est e d wit h a r a pi d a nti g e nic t est; 
1 0 1 2  
i n t h e c as e of a p ositi v e t est r es ult, p o d m e m b ers of t h e s y m pt o m atic p ers o n will b e 
1 0 1 3  
w e ari n g a m as k at all ti m es i n d o or a n d o ut d o or , exc e pt f or e ati n g, dri n ki n g, sl e e pi n g, 
1 0 1 4  
a n d s h o w eri n g.  
1 0 1 5  
•  All p artici p a nts w h o d e v el o p s y m pt o ms of C O VI D 1 9 d uri n g c a m p, t est p ositi v e f or 
1 0 1 6  
C O VI D 1 9 d uri n g c a m p, or ar e p art of t h e s a m e p o d as a p ers o n w h o d e v el o p e d 
1 0 1 7  
s y m pt o ms of C O VI D 1 9 or t est e d p ositi v e f or C O VI D 1 9 d uri n g c a m p, will b e as k e d t o 
1 0 1 8  
f oll o w u p vi a p h o n e wit h t h e st u d y t e a m 5-7 d a ys aft er disc h ar g e. All p ar tici p a nts w h o 
1 0 1 9  
d e v el o p s y m pt o ms of C O VI D 1 9 or t est p ositi v e f or C O VI D 1 9 wit hi n 7 d a ys aft er 
1 0 2 0  
disc h ar g e fr o m t h e st u d y a d missi o n will b e as k e d t o f oll o w u p vi a p h o n e wit h t h e st u dy 
1 0 2 1  
t e a m. 
1 0 2 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 4  of 6 6  
 
 
1 0 2 3  
T h e i nt e nsit y of a n a d v ers e e v e nt will b e r at e d o n a t hr e e-p oi nt  sc al e: ( 1) mil d, ( 2) m o d er at e, or 
1 0 2 4  
( 3) s e v er e. It is e m p h asiz e d t h at t h e t er m s e v er e is a m e as ur e of i nt e nsity: t h us, a s ev er e a d v ers e 
1 0 2 5  
e v e nt is n ot n ec ess aril y s eri o us . F or ex a m pl e, itc hi n g f o r s e v er al d a ys m a y b e r at e d as s e v er e, b ut 
1 0 2 6  
m a y n ot b e cli nic all y s eri o us.  
1 0 2 7  
•  MIL D: Us u all y tr a nsi e nt, r e q uir es n o s p eci al tr e at m e nt, a n d d o es n ot i nt erf er e wit h 
1 0 2 8  
t h e p artici p a nt’s d ail y acti viti es. 
1 0 2 9  
•  M O D E R A T E: Us u all y c a us es a l o w l e v el of i nc o n v e ni e nc e or c o nc e r n t o t h e p artici p a nt 
1 0 3 0  
a n d m a y i nt erf e r e wit h d ail y acti viti es b ut  is us u all y a m eli or at e d b y si mpl e t h er a p e utic 
1 0 3 1  
m e as ur es.  
1 0 3 2  
•  S E V E R E: I nt err u pts a p artici p a nt’s us u al d ail y acti viti es a n d g e n er all y r e q uir es s yst e mic 
1 0 3 3  
dr u g t h er a p y or ot h er tr e at m e nt.  
1 0 3 4  
 
1 0 3 5  
A d v ers e e v e nts will b e c o d e d p er t h e U V A I R B w e bsit e i nstr ucti o ns (i. e. mil d, m o d er at e, s e v er e) . 
1 0 3 6  
T h e M M will r e vi e w t h e i n v esti g at or’s ass ess m e nt of c a us ality a n d m a y a gr e e or dis a gr e e . B ot h 
1 0 3 7  
t h e i n v esti g at or’s a n d M M ’s  ass ess m e nts will b e r ec or d e d. T h e M M  will h a v e t h e fi n al s a y i n 
1 0 3 8  
d et er mi ni n g t h e c a us alit y.  
1 0 3 9  
A d v ers e e v e nts t h at c o nti n u e aft er t h e p artici p a nt’s disc o nti n u ati o n or c o m pl eti o n of t h e st u d y 
1 0 4 0  
will b e f oll o w e d u ntil t h eir m e dic al o utc o m e is d et er mi n e d or u ntil n o f ur t h er c h a n g e i n t h e 
1 0 4 1  
c o n diti o n is ex p ect e d. 
1 0 4 2  
 
1 0 4 3  
T h e o utc o m e of e ac h r e p ort a bl e a d v ers e e v e nt will b e cl assifi e d b y t h e i n v esti g at or as f oll o ws:  
1 0 4 4  
•  R E C O V E R E D/ R E S OL V E D – T h e  p artici p a nt  r ec o v er e d  fr o m  t h e  A E/ S A E  wit h o ut  
1 0 4 5  
s e q u el a e. R ec or d t h e A E/ S A E st o p d at e.  
1 0 4 6  
•  R E C O V E R E D/ R E S OL V E D WI T H S E Q U EL A E – T h e e v e nt p ersist e d a n d h a d st a biliz e d 
1 0 4 7  
wit h o ut c h a n g e i n t h e e v e nt a ntici p at e d . R ec or d t h e A E/ S A E st o p d at e.  
1 0 4 8  
•  F A T AL – A f at al o utc o m e is d efi n e d as t h e S A E t h at r es ult e d i n d e at h . O nl y t h e e v e n t 
1 0 4 9  
t h at w as t h e c a us e of d e at h s h o ul d b e r e p ort e d as f at al. A Es/ S A Es t h at w er e o n g oi n g 
1 0 5 0  
at t h e ti m e of d e at h; h o w e v er, w er e n ot t h e c a us e of d e at h, will b e r ec or d e d as 
1 0 5 1  
“r es ol v e d” at t h e ti m e of d e at h. 
1 0 5 2  
•  N O T R E C O V E R E D/ N O T R E S OL V E D ( O N G OI N G) – A n o n g oi n g A E/ S A E is d efi n e d as t h e 
1 0 5 3  
e v e nt w as o n g oi n g wit h a n u n d et er mi n e d o utc o m e.  
1 0 5 4  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 5  of 6 6  
 
•  A n o n g oi n g o utc o m e will r e q uir e f oll o w -u p b y t h e sit e i n or d er t o d et er mi n e t h e fi n al 
1 0 5 5  
o utc o m e of t h e A E/ S A E.  
1 0 5 6  
•  T h e o utc o m e of a n o n g oi n g e v e nt at t h e ti m e of d e at h t h at w as n ot t h e c a us e of d e at h, 
1 0 5 7  
will b e u p d at e d a n d r ec or d e d as “r es ol v e d” wit h t h e d at e of d e at h r ec or d e d as t h e 
1 0 5 8  
st o p d at e. 
1 0 5 9  
•  U N K N O W N – A n u n k n o w n o utc o m e is d efi n e d as a n i n a bility t o acc ess t h e p artici p a nt 
1 0 6 0  
or t h e p artici p a nt’s r ec or ds t o d et er mi n e t h e o utc o m e (f or ex a m pl e, a p artic i p a nt t h at 
1 0 6 1  
w as l ost t o f oll o w -u p).  
1 0 6 2  
All cli nic all y si g nific a nt a b n or m aliti es of cli nic al l a b or at or y m e as ur e m e nts or a dv ers e e v e nts 
1 0 6 3  
occ urri n g d uri n g t h e st u d y a n d c o nti n ui n g at st u d y t er mi n ati o n s h o ul d b e f oll o w e d b y t h e 
1 0 6 4  
p artici p a nt’s p h ysici a n a n d e v al u at e d  wit h a d diti o n al t ests (if n ec ess ar y) u ntil di a g n osis of t h e 
1 0 6 5  
u n d erl yi n g c a us e, or r es ol uti o n . F oll o w -u p i nf or m ati o n s h o ul d b e r ec or d e d o n s o urc e d oc u m e nts.  
1 0 6 6  
If a n y r e p ort e d a d v ers e e v e nts ar e pr es e nt w h e n a p artici p a nt c o m pl et es t h e st u d y, or if a 
1 0 6 7  
p artici p a nt  is  wit h dr a w n  fr o m  t h e  st u dy  d u e  t o  a n  a d v ers e  e v e nt,  t h e  p artici p a nt  will  b e  
1 0 6 8  
c o nt act e d f or r e-e v al u ati o n wit hi n 2 w e e ks . If t h e a d v ers e e v e nt h as n ot r es ol v e d, a d diti o n al 
1 0 6 9  
f oll o w-u p will b e p erf or m e d as a p pr o pri at e . Ev er y eff ort s h o ul d b e m a d e b y t h e I nv esti g at or or 
1 0 7 0  
d el e g at e t o c o nt act t h e p artici p a nt u ntil t h e a d v ers e e v e nt h as r es ol v e d or st a biliz e d.  
1 0 7 1  
 
1 0 7 2  
All U A D Es, A D Es, d e vic e c o m pl ai nts, a n d d e vic e m alf u ncti o ns will b e r e p ort e d irr es p ecti v e of 
1 0 7 3  
w h et h er a n a d v ers e e v e nt occ urr e d, exc e pt i n t h e f oll o wi n g circ u mst a nc es.  
1 0 7 4  
T h e f oll o wi n g d e vic e iss u es ar e a ntici p at e d a n d will n ot b e r e p ort e d b ut will r e p ort e d as a n 
1 0 7 5  
A d v ers e Ev e nt if t h e crit eri a f or A E r e p orti n g d escri b e d a b o v e ar e m et:  
1 0 7 6  
•  C o m p o n e nt disc o n n ecti o ns  
1 0 7 7  
•  C G M s e ns ors l asti n g f e w er t h a n t h e n u m b er of d a ys ex p ect e d p er C G M l a b eli n g  
1 0 7 8  
•  C G M t a p e a d h er e nc e iss u es  
1 0 7 9  
•  P u m p i nf usi o n s et occl usi o n n ot l e a di n g t o k et osis  
1 0 8 0  
•  B att er y  lif es p a n  d efici e ncy  d u e  t o  i n a d e q u at e  c h ar gi n g  or  ext e nsi v e  wir el ess  
1 0 8 1  
c o m m u nic ati o n 
1 0 8 2  
•  I nt er mitt e nt d e vic e c o m p o n e nt disc o n n ecti o ns/c o m m u nic ati o n f ail ur es n ot l e a di n g 
1 0 8 3  
t o s yst e m r e pl ac e m e nt 
1 0 8 4  
•  D e vic e  iss u es  cl e arl y  a d dr ess e d  i n  t h e  us er  g ui d e  m a n u al  t h at  d o  n ot  r e q uir e  
1 0 8 5  
a d diti o n al tr o u bl es h o oti n g  
1 0 8 6  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 6  of 6 6  
 
•  S ki n r e acti o ns fr o m C G M s e ns or pl ac e m e nt or p u m p i nf usi o n s et pl ac e m e nt t h at d o 
1 0 8 7  
n ot m e et crit eri a f or A E r e p orti n g  
1 0 8 8  
 
1 0 8 9  
•  U A D Es m ust b e r e p ort e d wit hi n 1 0 w or ki n g d a ys t o t h e F D A  aft er t h e s p o ns or first 
1 0 9 0  
r ec ei v es n otic e of t h e a d v ers e eff ect. 
1 0 9 1  
•  Ot h er r e p ort a bl e a d v ers e e v e nts, d e vic e m alf u ncti o ns ( wit h or wit h o ut a n a d v ers e 
1 0 9 2  
e v e nt) a n d d e vic e c o m pl ai nts s h o ul d b e r e p ort e d pr o m ptl y, b ut t h er e is n o f or m al 
1 0 9 3  
r e q uir e d r e p orti n g p eri o d. 
1 0 9 4  
•  T h e  I D E S p o ns or will i n v esti g at e t h e U A D E a n d if i n dic at e d, r e p ort t h e r es ults of t h e 
1 0 9 5  
i n v esti g ati o n t o t h e I R Bs, F D A, a n d M M  wit hi n 1 0 w or ki n g d a ys of t h e st u d y t e a m 
1 0 9 6  
b ec o mi n g a w ar e of t h e U A D E p er 2 1 C F R 8 1 2. 4 6( b) ( 2).  
1 0 9 7  
•  T h e M M  will  d et er mi n e if t h e U A D E pr es e nts a n u nr e as o n a bl e ris k t o p artici p a nts. If 
1 0 9 8  
s o, t h e M M  m ust e ns ur e t h at all i n v esti g ati o ns, or p arts of i n v esti g ati o ns pr es e nti n g 
1 0 9 9  
t h at ris k, ar e t er mi n at e d as s o o n as p ossi bl e b ut n o l at er t h a n 5 w or ki n g d a ys aft er t h e 
1 1 0 0  
M M  m a k es t his d et er mi n ati o n a n d n o l at er t h a n 1 5 w or ki n g  d a ys aft er first r ec ei pt 
1 1 0 1  
n otic e of t h e U A D E.  
1 1 0 2  
•  I n t h e c as e of a d e vic e s yst e m c o m p o n e nt m alf u ncti o n ( e. g. p u m p, C G M, c o ntr ol 
1 1 0 3  
al g orit h m), i nf or m ati o n will b e f or w ar d e d t o t h e r es p o nsi bl e m a n uf act ur er b y t h e 
1 1 0 4  
st u d y p ers o n n el. 
1 1 0 5  
 
1 1 0 6  
 P artici p a nt Disc o nti n u ati o n  
1 1 0 7  
R ul es f or disc o nti n ui n g st u d y d e vic e us e ar e d escri b e d b el o w : 
1 1 0 8  
•  T h e  i n v esti g at or  b eli e v es  it  is  u ns af e  f or  t h e  p artici p a nt  t o  c o nti n u e  o n  t h e  
1 1 0 9  
i nt er v e nti o n. T his c o ul d b e d u e t o t h e d e v el o p m e nt of a n e w m e dic al c o n diti o n or 
1 1 1 0  
w ors e ni n g of a n existi n g c o n diti o n; or p artici p a nt b e h a vi or c o ntr ar y t o t h e i n dic ati o ns 
1 1 1 1  
f or us e of t h e d e vic e t h at i m p os es o n t h e p artici p a nt’s s af ety 
1 1 1 2  
•  T h e p artici p a nt r e q u ests t h at t h e tr e at m e nt b e st o p p e d  
1 1 1 3  
•  O n e e pis o d e  of D K A 
1 1 1 4  
•  O n e e pis o d e of  s e v er e h y p o gl yc e mi a as d efi n e d i n s ecti o n 1 1. 2. 1 . 
1 1 1 5  
•  D e v el o p m e nt of C O VI D -1 9 s y m pt o ms or p ositi v e C O VI D -1 9 t est  
1 1 1 6  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 7  of 6 6  
 
 S us p e n di n g/ St o p pi n g O v er all St u d y  
1 1 1 7  
I n t h e c as e of a n u n a ntici p at e d s yst e m m alf u ncti o n r es ulti n g i n a s e v er e h y p o gl yc e mi a or s e v er e 
1 1 1 8  
h y p er gl yc e mi a  e v e nt  ( as  d efi n e d  i n  s ecti o n  1 1. 2 ),  us e  of  t h e  st u d y d e vic e  s yst e m  will  b e 
1 1 1 9  
s us p e n d e d w hil e t h e pr o bl e m is di a g n os e d. 
1 1 2 0  
I n t h e e v e nt t h at t w o disti nct e pis o d es of D K A or t w o disti nct s e v er e h y p o gl yc e mi a e v e nts as 
1 1 2 1  
d efi n e d i n s ecti o n 1 1. 2  occ ur, t h e o v er all st u d y w o ul d b e s us p e n d e d w hil e t h e u n d erl yi n g 
1 1 2 2  
c o n diti o ns ar e d et er mi n e d. 
1 1 2 3  
I n a d diti o n, st u d y acti viti es c o ul d b e si mil arl y s us p e n d e d if t h e m a n uf act ur er of a ny c o nstit u e nt 
1 1 2 4  
stu d y d e vic e r e q uir es st o p p a g e of d e vic e us e f or s af ety r e as o ns ( e. g. , pr o d uct r ec all) . T h e aff ect e d 
1 1 2 5  
st u d y acti viti es m a y r es u m e if t h e u n d erlyi n g pr o bl e m c a n b e c orr ect e d b y a pr ot oc ol or s yst e m 
1 1 2 6  
m o dific ati o n t h at will n ot i n v ali d at e t h e r es ults o bt ai n e d pri or t o s us p e nsi o n. T h e st u d y M M  will 
1 1 2 7  
r e vi e w all a d v ers e e v e nts a n d a d v ers e d evic e e v e nts t h at ar e r e p ort e d d uri n g t h e st u d y a n d will 
1 1 2 8  
r e vi e w c o m pil e d s af et y d at a at p eri o dic i nt er v als ( g e n er all y ti m e d t o t h e r e vi e w of c o m pil e d 
1 1 2 9  
s af et y d at a b y th e M M ). T h e M M m a y r e q u est s us p e nsi o n of st u d y acti viti es or st o p p a g e of t h e 
1 1 3 0  
st u d y if d e e m e d n ec ess ar y b as e d o n t h e t ot ality of s af ety d at a a v ail a bl e. 
1 1 3 1  
 
1 1 3 2  
A M M  will r e vi e w all D K A a n d s e v er e h y p o gl yc e mi a irr es p ecti v e of r el at e d n ess t o st u d y d e vic e 
1 1 3 3  
us e,  a n d  all  s eri o us  e v e nts  (i ncl u di n g  U A D Es)  r el at e d  t o  st u d y  d e vic e  us e  at  t h e  ti m e  of  
1 1 3 4  
occ urr e nc e. T h e M M c a n r e q u est m o dific ati o ns t o t h e st u d y pr ot oc ol or s us p e nsi o n or o utri g ht 
1 1 3 5  
st o p p a g e of t h e st u d y if d e e m e d n ec ess ary b as e d o n t h e t ot ality of s af ety d at a a v ail a bl e. D et ails 
1 1 3 6  
r e g ar di n g M M r e vi e w will b e d oc u m e nt e d i n a s e p ar at e M M d oc u m e nt .  
1 1 3 7  
 
1 1 3 8  
A d at a br e ac h is d efi n e d i n t h e H I T E C H Act ( 4 3 U S C 1 7 9 3 2) as a n u n a ut h oriz e d ac q uisiti o n, acc ess, 
1 1 3 9  
or us e of pr ot ect e d h e alt h i nf or m ati o n ( P HI) t h at c o m pr o mis es t h e s ec urity or pri v acy of s uc h 
1 1 4 0  
i nf or m ati o n.  
 
1 1 4 1  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 8  of 6 6  
 
C h a pt er 1 2:  Misc ell a n e o us C o nsi d er ati o ns  
1 1 4 2  
 
1 1 4 3  
P artici p a nts usi n g gl ulisi n e at t h e ti m e of e nr oll m e nt will b e as k e d t o c o nt act t h eir p ers o n al 
1 1 4 4  
p h ysici a n t o c h a n g e t h eir pr escri b e d p ers o n al i ns uli n t o lis pr o or as p art f or t h e d ur ati o n of t h e 
1 1 4 5  
tri al. 
1 1 4 6  
T h e st u d y d e vic es (st u d y i ns uli n p u m p, st u d y C G M) m ust b e r e m o v e d b ef or e M a g n etic R es o n a nc e 
1 1 4 7  
I m a gi n g ( M RI), C o m p ut e d T o m o gr a p h y ( C T) or di at h er m y tr e at m e nt. P artici p a nts m a y c o nti n u e 
1 1 4 8  
i n t h e tri al aft er t e m p or aril y disc o nti n ui n g us e if r e q uiri n g o n e of t h e tr e at m e nts a b o v e. 
1 1 4 9  
 
1 1 5 0  
P arti ci p ati o n i n t h e st u d y is v ol u nt ar y. P artici p a nt m a y wit h dr a w at a n y ti m e . F or  p artici p a nts 
1 1 5 1  
w h o d o wit h dr a w  fr o m t h e st u d y, t h e st u d y t e a m will d et er mi n e if t h eir d at a will b e us e d i n 
1 1 5 2  
a n al ysis.  
1 1 5 3  
 
1 1 5 4  
F or s ec urit y a n d c o nfi d e nti alit y p ur p os es, p artici p a nt s will b e assi g n e d a n i d e ntifi er t h at will b e 
1 1 5 5  
us e d i nst e a d of t h eir n a m e . Pr ot ect e d h e alt h i nf or m ati o n g at h er e d f or  t his st u d y m a y b e s h ar e d 
1 1 5 6  
wit h t h e t hir d-p art y  c oll a b or at ors. D e -i d e ntifi e d p artici p a nt  i nf or m ati o n m a y als o b e pr o vi d e d t o 
1 1 5 7  
c oll a b or at ors i n v ol v e d i n t h e st u d y aft er t h e a p pr o pri at e r es e arc h a gr e e m e nt h as b e e n ex ec ut e d.  
1 1 5 8  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 5 9  of 6 6  
 
C h a pt er 1 3:  St atistic al C o nsi d er ati o n  
1 1 5 9  
 
1 1 6 0  
T h e st u d y f oll o ws a d o u bl e -bli n d r a n d o miz e d cr oss o v er d esi g n, c o m p ari n g gl yc e mic c o ntr ol 
1 1 6 1  
o bt ai n e d usi n g t h e U V A H CL s yst e m – US S Vir gi ni a – al o n e ( co ntr ol) or i n c o m bi n ati o n wit h a 
1 1 6 2  
s m art  b ol us  c alc ul at or  i nf or m e d  b y  r e al-ti m e  SI  ass ess m e nts  ( e x p eri m e nt al).  All  st u d y  
1 1 6 3  
p artici p a nts will u n d er g o b ot h tr e at m e nt c o n diti o ns , i n diff er e nt or d ers, d efi ni n g t w o st u d y ar ms 
1 1 6 4  
as s h o w n i n Fi g ur e 1 . R a n d o miz ati o n ( 1: 1) will d et er mi n e w h et h er a p artici p a nt s h o ul d u n d er g o 
1 1 6 5  
t h e c o ntr ol or ex p eri m e nt al tr e at m e nt c o n diti o n first.  
1 1 6 6  
 
1 1 6 7  
S a m pl e siz e w as d et er mi n e d b y p o w er a n al ysis usi n g G * P o w er 3. 1  c o nsi d eri n g a p air e d t -t est as 
1 1 6 8  
t h e st atistic al t est, c o m p ari n g co ntr ol gr o u p t o e x p eri m e nt al gr o u p  on t h e pri m ar y effic acy 
1 1 6 9  
e n d p oi nt . Eff ect siz e w as d et er mi n e d b as e d o n t h e r es ults o bt ai n e d fr o m t h e pil ot cli nic al t esti n g 
1 1 7 0  
of t h e SI -i nf or m e d b ol us c alc ul at or i n o p e n-l o o p c o n diti o ns t o b e dz = 0. 6 1 4. A t ot al s a m pl e siz e of 
1 1 7 1  
N = 3 0 s u bj ects  w as o bt ai n e d c o nsi d eri n g a 0. 6 6 c orr el ati o n b et w e e n gr o u ps, 9 0 % p o w er, a n d 
1 1 7 2  
𝛼𝛼= 0. 0 5 . 
1 1 7 3  
 
1 1 7 4  
 Pri m ar y Effic ac y E n d p oi nt  
1 1 7 5  
T h e pri m ar y e n d p oi nt will b e t h e l o w bl o o d gl uc os e i n d ex (L B GI) c o m p ut e d fr o m C G M c oll ect e d 
1 1 7 6  
i n t h e f o ur h o urs f oll o wi n g t h e di n n er m e al. 
1 1 7 7  
 S ec o n d ar y O utc o m e s 
1 1 7 8  
S ec o n d ar y e n d p oi nts will i ncl u d e  a n al ysis o v er f o ur diff er e nt ti m e i nt er v als:   
1 1 7 9  
1.  
t h e di n n er p ost pr a n di al p eri o d (i. e., t h e f o ur h o urs f oll o wi n g di n n er) 
1 1 8 0  
2.  
d a yti m e , i. e., br e a kf ast t o b e dti m e  
1 1 8 1  
3.  
ni g htti m e, i. e., b e dti m e t o br e a kf ast  
1 1 8 2  
4.  
2 4 h o urs  
1 1 8 3  
 
1 1 8 4  
T h e gl yc e mic o utc o m es c o m p ut e d o v er t h e f o ur h oriz o ns will b e:  
1 1 8 5  
•  p erc e nt a g e of ti m e s p e nt b el o w 7 0 m g/ dL  
1 1 8 6  
•  p erc e nt a g e of ti m e s p e nt i n 7 0 -1 4 0 a n d 7 0 -1 8 0 m g/ dL  
1 1 8 7  
•  p erc e nt a g e of ti m e s p e nt a b o v e 1 8 0 a n d 2 5 0 m g/ dL  
1 1 8 8  
•  t h e hi g h bl o o d gl uc os e i n d ex 
1 1 8 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 0  of 6 6  
 
•  a v er a g e C G M  
1 1 9 0  
•  C G M c o effici e nt of v ari ati o n  
1 1 9 1  
•  T ot al n u m b er a n d a m o u nt of c ar b o h y dr at e a d mi nist er e d as r esc u e tr e at m e nts  
1 1 9 2  
All gl yc e mic o utc o m es ( pri m ar y effic acy e n d p oi nt a n d s ec o n d ar y o utc o m es) will b e c o m p ut e d 
1 1 9 3  
b as e d o n C G M r ec or ds. T h e pri m ar y a n al ysis will f oc us o n t h e p ost pr a n di al p eri o d, b ut ot h er 
1 1 9 4  
a n al ys es will e v al u at e diff er e nt ti m e i nt erv als t o ass ess w h et h er t h e i m p act o n t h e p ost pr a n di al 
1 1 9 5  
p eri o d will b e i nfl u e nti al e n o u g h t o i m p act t h e o v er all d ail y c o ntr ol. P air e d t -t ests or n o n-
1 1 9 6  
p ar a m etric Wilc ox o n si g n e d -r a n k t ests will b e us e d t o c o m p ar e t h e c o ntr ol a n d ex p eri m e nt al 
1 1 9 7  
ar ms o n t h e diff er e nt gl yc e mic o utc o m es, i n c as e of n or m all y/ n o n -n or m all y distri b ut e d s a m pl es 
1 1 9 8  
r es p ecti v el y (S h a pir o-Wil k t est). Si g nific a nc e l e v el will b e s et at a P v al u e l ess t h a n 0. 0 5. All 
1 1 9 9  
st atistic al a n al ys es will b e c o m p ut e d i n S PS S St atistics 2 6 (I B M). 
1 2 0 0  
 
1 2 0 1  
S af et y e n d p oi nts ar e  s ec o n d ar y o utc o m es a d dr essi n g h y p o gl yc e mi a a n d h y p er gl yc e mi a, i. e., 
1 2 0 2  
p erc e nt a g e of ti m e b el o w 7 0  m g/ dL a n d a b o v e 2 5 0 m g/ dL, a n d t ot al n u m b er a n d a m o u nt of 
1 2 0 3  
c ar b o h y dr at e a d mi nist er e d as r esc u e tr e at m e nts. 
1 2 0 4  
 
1 2 0 5  
B as eli n e d e m o gr a p hic a n d cli nic al c h ar act eristics of t h e c o h ort of all r a n d o miz e d p artici p a nts will 
1 2 0 6  
b e s u m m ariz e d i n a t a bl e usi n g s u m m ar y st atistics  a p pr o pri at e t o t h e distri b uti o n of e ac h 
1 2 0 7  
v ari a bl e. D escri pti v e st atistics will b e dis pl a y e d o v er all a n d b y tr e at m e nt gr o u p.  
1 2 0 8  
Will i ncl u d e:  
1 2 0 9  
•  A g e  
1 2 1 0  
•  H b A 1c  
1 2 1 1  
•  G e n d er  
1 2 1 2  
•  R ac e/ et h nicit y  
1 2 1 3  
•  Di a b et es d ur ati o n  
1 2 1 4  
•  B MI  
1 2 1 5  
 
1 2 1 6  
T h e f oll o wi n g t a b ul ati o ns a n d a n al ys es will b e p erf or m e d b y tr e at m e nt gr o u p t o ass ess d e vic e 
1 2 1 7  
iss u es: 
1 2 1 8  
•  D e vic e m alf u ncti o ns r e q uiri n g st u d y t e a m c o nt act a n d ot h er r e p ort e d d e vic e iss u es  
1 2 1 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 1  of 6 6  
 
•  S e ns or  p erf or m a nc e  m etrics  ( diff er e nc e,  a bs ol ut e  r el ati v e  diff er e nc e,  a n d  
1 2 2 0  
I nter n ati o n al  Or g a niz ati o n  f or  St a n d ar diz ati o n  crit eri a) – if a p plic a bl e, b y s e ns or 
1 2 2 1  
v ersi o n. 
1 2 2 2  
•  % ti m e C G M d at a a v ail a bl e - o v er all a n d by m o nt h  
1 2 2 3  
T h e f oll o wi n g t a b ul ati o ns will b e p erf or m e d f or t h e Ex p eri m e nt al ar m o nl y:  
1 2 2 4  
•  P erf or m a nc e m etrics, d escri bi n g t h e CL C s yst e m a n d its c o m p o n e nts li k e: 
1 2 2 5  
a.  % ti m e C G M d at a w er e a v ail a bl e t o t h e CL C s yst e m – o v er all a n d b y m o nt h  
1 2 2 6  
b.  % ti m e i n diff er e nt o p er ati o n al m o d es p er w e e k - o v er all a n d b y m o nt h  
1 2 2 7  
c. R at e of diff er e nt f ail ur e e v e nts a n d al ar ms p er 4 8  h o urs r ec or d e d b y t h e CL C 
1 2 2 8  
s yste m – o v er all a n d b y m o nt h  
 
1 2 2 9  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 2  of 6 6  
 
C h a pt er 1 4:  D at a C oll ecti o n a n d M o nit ori n g  
1 2 3 0  
 
1 2 3 1  
T h e st u d y d at a ar e c oll ect e d t hr o u g h a c o m bi n ati o n of c as e r e p ort f or ms ( el ectr o nic a n d p a p er) 
1 2 3 2  
a n d  el ectr o nic  d e vic e  d at a  fil es  o bt ai n e d  fr o m  t h e  s oft w ar e  a n d  i n di vi d u al  h ar d w ar e  
1 2 3 3  
c o m p o n e nts. T h es e el ectr o nic d e vic e fil es a n d el ectr o nic C R Fs ar e c o nsi d er e d t h e pri m ar y s o urc e 
1 2 3 4  
d oc u m e nt ati o n.  
1 2 3 5  
W h e n d at a ar e dir ectl y c oll ect e d i n el ectr o nic c as e r e p ort f or ms, t his will b e c o nsi d er e d t h e 
1 2 3 6  
s o urc e d at a. R ec or ds will b e m ai nt ai n e d i n acc or d a nc e wit h I C H E 6 a n d i nstit uti o n al r e g ul at or y 
1 2 3 7  
r e q uir e m e nts f or t h e pr ot ecti o n of c o nfi d e nti ality of p artici p a nts. 
1 2 3 8  
 
1 2 3 9  
St u d y d oc u m e nts s h o ul d b e r et ai n e d f or a mi ni m u m of 2 y e ars aft er t h e l ast a p pr o v al of a 
1 2 4 0  
m ar k eti n g  a p plic ati o n i n a n I C H r e gi o n a n d u ntil t h er e ar e n o p e n di n g or c o nt e m pl at e d m ar k eti n g 
1 2 4 1  
a p plic ati o ns  i n  a n  I C H  r e gi o n  or  u ntil  at  l e ast  2  y e ars  h a v e  el a ps e d  si nc e  t h e  f or m al  
1 2 4 2  
disc o nti n u ati o n of cli nic al d e v el o p m e nt of t h e i n v esti g ati o n al pr o d uct.  T h es e d oc u m e nts s h o ul d 
1 2 4 3  
b e r et ai n e d f or a l o n g er p eri o d, h o w e v er, if r e q uir e d b y l oc al r e g ul ati o ns. N o r ec or ds will b e 
1 2 4 4  
d estr o y e d wit h o ut t h e writt e n c o ns e nt of t h e s p o ns or, if a p plic a bl e . It is t h e r es p o nsi bility of t h e 
1 2 4 5  
s p o ns or t o i nf or m t h e i n v esti g at or w h e n t h es e d oc u m e nts n o l o n g er n e e d t o b e r et ai n e d.  
1 2 4 6  
 
1 2 4 7  
A pr ot oc ol d e vi ati o n is a n y n o nc o m pli a nc e wit h t h e cli nic al tri al pr ot oc ol, G o o d Cli nic al Pr actic es 
1 2 4 8  
( G C P),  or  pr oc e d ur e  r e q uir e m e nts.  T h e  n o nc o m pli a nc e  m a y  b e  eit h er  o n  t h e  p art  of  t h e  
1 2 4 9  
p artici p a nt, t h e i n v esti g at or, or t h e st u d y sit e st aff. As a r es ult of d e vi ati o ns, c orr ecti v e acti o ns 
1 2 5 0  
m a y b e d e v el o p e d b y t h e sit e a n d i m pl e m e nt e d as a p pr o pri at e. M aj or d e vi ati o ns will b e r e p ort e d 
1 2 5 1  
t o t h e I R B-H S R wit hi n 7 c al e n d ar d a ys of w h e n t h e st u d y t e a m b ec o m es a w ar e of  t h e e v e nt.  
1 2 5 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 3  of 6 6  
 
C h a pt er 1 5:  Et hics/ Pr ot ecti o n of H u m a n P artici p a nts  
1 2 5 3  
 
1 2 5 4  
T h e i n v esti g at or will e ns ur e t h at t his st u d y is c o n d uct e d i n f ull c o nf or mity wit h R e g ul ati o ns f or 
1 2 5 5  
t h e Pr ot ecti o n of H u m a n P artici p a nts of R es e arc h c o difi e d i n 4 5 C F R P art 4 6, 2 1 C F R P art 5 0, 2 1 
1 2 5 6  
C F R P art 5 6, a n d/ or t h e I C H E 6.  
1 2 5 7  
 
1 2 5 8  
T h e pr ot oc ol, i nf or m e d c o ns e nt f or m(s), r ecr uit m e nt m at eri als, a n d all p artici p a nt m at eri als will 
1 2 5 9  
b e s u b mitt e d t o t h e I R B f or r e vi e w a n d a p pr o v al. A p pr o v al of b ot h t h e pr ot oc ol a n d t h e c o ns e nt 
1 2 6 0  
f or m m ust b e o bt ai n e d b ef or e a n y p artici p a nt is e nr oll e d. A n y a m e n d m e nt t o t h e pr ot oc ol will 
1 2 6 1  
r e q uir e r e vi e w a n d a p pr o v al b y t h e I R B b ef or e t h e c h a n g es ar e i m pl e m e nt e d t o t h e st u d y. All 
1 2 6 2  
c h a n g es t o t h e c o ns e nt f or m will b e I R B a p pr o v e d; a d et er mi n ati o n will b e m a d e r e g ar di n g 
1 2 6 3  
w h et h er pr e vi o usl y c o ns e nt e d p artici p a nts n e e d t o b e r e -c o ns e nt e d. 
1 2 6 4  
 
1 2 6 5  
 C o ns e nt Pr oc e d ur es a n d D oc u m e nt ati o n  
1 2 6 6  
I nf or m e d c o ns e nt is a pr oc ess t h at is i niti at e d pri or t o a n i n di vi d u al’s a gr e e m e nt t o p artici p at e i n 
1 2 6 7  
t h e st u d y a n d c o nti n u es t hr o u g h o ut t h e i n divi d u al’s st u d y p artici p ati o n. Ext e nsi v e disc ussi o n of 
1 2 6 8  
ris ks a n d p ossi bl e b e n efits of p artici p ati o n will b e pr o vi d e d. C o ns e nt f or ms will b e I R B a p pr o v e d 
1 2 6 9  
a n d t h e p artici p a nt will b e as k e d t o r e a d a n d r e vi e w t h e d oc u m e nt. T h e i n v esti g at or or t h eir 
1 2 7 0  
d el e g at e wi ll ex pl ai n t h e r es e arc h st u d y t o t h e p artici p a nt  a n d a ns w er a n y q u esti o ns t h at m a y 
1 2 7 1  
aris e. All p artici p a nts will r ec ei v e a v er b al ex pl a n ati o n i n t er ms s uit e d t o t h eir c o m pr e h e nsi o n of 
1 2 7 2  
t h e  p ur p os es, pr oc e d ur es, a n d  p ot e nti al  ris ks of  t h e st u d y a n d  of  t h eir ri g hts  as  r es e arc h  
1 2 7 3  
p artici p a nts. P artici p a nt  will h a v e t h e o p p ort u nity t o c ar ef ull y r e vi e w t h e writt e n c o ns e nt f or m 
1 2 7 4  
a n d as k q u esti o ns pri or t o si g ni n g.  
1 2 7 5  
T h e p artici p a nt will si g n t h e i nf or m e d c o ns e nt d oc u m e nt pri or t o a n y pr oc e d ur es b ei n g d o n e 
1 2 7 6  
s p ecific all y for  t h e  st u d y.  A  c o p y of  t h e  i nf or m e d  c o ns e nt  d oc u m e nt  will  b e  gi v e n  t o t h e 
1 2 7 7  
p artici p a nt f or t h eir r ec or ds. T h e ri g hts a n d w elf ar e of t h e p artici p a nts will b e pr ot ect e d b y 
1 2 7 8  
e m p h asizi n g t o t h e m t h at t h e q u alit y of t h eir m e dic al c ar e will n ot b e a d v ers el y aff ec t e d if t h e y 
1 2 7 9  
d ecli n e t o p artici p at e i n t his st u d y.  
1 2 8 0  
 P artici p a nt a n d D at a C o nfi d e nti alit y  
1 2 8 1  
T h e st u d y m o nit or, r e pr es e nt ati v es of t h e I R B or d e vic e c o m p a n y s u p pl yi n g st u d y pr o d uct m a y 
1 2 8 2  
i ns p ect all d oc u m e nts a n d r ec or ds r e q uir e d t o b e m ai nt ai n e d b y t h e i n v esti g ator, i ncl u di n g b ut 
1 2 8 3  
n ot li mit e d t o, m e dic al r ec or ds ( offic e, cli nic, or h os pit al) f or t h e p artici p a nts i n t his st u d y .  
1 2 8 4  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 4  of 6 6  
 
T h e st u d y p artici p a nt’s c o nt act i nf or m ati o n will b e s ec ur el y st or e d at t h e cli nic al sit e f or i nt er n al 
1 2 8 5  
us e d uri n g t h e st u d y. At t h e e n d of t h e st u d y, all r ec or ds will c o nti n u e t o b e k e pt i n a s ec ur e 
1 2 8 6  
l oc ati o n f or as l o n g a p eri o d as dict at e d by l oc al I R B a n d I nstit uti o n al r e g ul ati o ns. 
1 2 8 7  
St u d y  p artici p a nt  r es e arc h  d at a,  w hic h  is  f or  p ur p os es  of  st atistic al  a n al ysis  a n d  sci e ntific  
1 2 8 8  
r e p orti n g, will b e tr a ns mitt e d t o a n d st or e d at t h e U ni v ersity of Vir gi ni a C e nt er f or Di a b et es 
1 2 8 9  
T ec h n ol o gy. T h e st u d y d at a e ntr y a n d st u d y m a n a g e m e nt s yst e ms us e d b y r es e arc h st aff will b e 
1 2 9 0  
s ec ur e d a n d p ass w or d pr ot ect e d. At t h e e n d of t h e st u d y, all st u d y d at a b as es m a y b e d e -
1 2 9 1  
i d e ntifi e d a n d arc hi v e d at t h e U ni v ersity of Vir gi ni a C e nt er f or Di a b et es T ec h n ol o gy. 
1 2 9 2  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 5  of 6 6  
 
C h a pt er 1 6:  R ef er e nc es  
1 2 9 3  
1.  
C hil dr e n a n d A d ol esc e nts: St a n d ar ds of M e dic al C ar e i n Di a b et es -2 0 2 0. Di a b et es c ar e  
1 2 9 4  
2 0 2 0; 4 3: S 1 6 3 -s 1 8 2 
1 2 9 5  
2.  
Br o w n  S A,  J i a n g  B,  Mc El w e e-M all o y  M,  W a k e m a n  C,  Br et o n  M D.  Fl uct u ati o ns  of  
1 2 9 6  
Hy p er gl yc e mi a a n d I ns uli n S e nsiti vity Ar e Li n k e d t o M e nstr u al C ycl e P h as es i n W o m e n 
1 2 9 7  
Wit h T 1 D. J o ur n al of di a b et es sci e nc e a n d t ec h n ol o gy  2 0 1 5; 9: 1 1 9 2 -1 1 9 9  
1 2 9 8  
3.  
C arr oll  M F,  Sc h a d e  DS.  T h e  d a w n  p h e n o m e n o n  r e visit e d:  i m plic ati o ns  f or  di a b et es  
1 2 9 9  
t h er a p y. E n d ocr Pr act 2 0 0 5; 1 1: 5 5 -6 4  
1 3 0 0  
4.  
B or g h o uts L B, K eiz er H A. Ex ercis e a n d i ns uli n s e nsiti vity: a r e vi e w. I nt J S p orts M e d  2 0 0 0; 
1 3 0 1  
2 1: 1 -1 2  
1 3 0 2  
5.  
M ar a n  A,  P a v a n  P,  B o ns e m bi a nt e  B,  Br u gi n  E,  Er m ol a o  A,  A v o g ar o  A,  Z acc ari a  M.  
1 3 0 3  
C o nti n u o us  gl uc os e  m o nit ori n g  r e v e als  d el a y e d  n oct ur n al  h y p o gl yc e mi a  aft er  
1 3 0 4  
i nt er mitt e nt hi g h-i nt e nsit y ex ercis e i n n o ntr ai n e d p ati e nts wit h ty p e 1 di a b et es. Di a b et es 
1 3 0 5  
t ec h n ol o gy & t h er a p e utics 2 0 1 0; 1 2: 7 6 3 -7 6 8  
1 3 0 6  
6.  
L a n dt K W, C a m p ai g n e B N, J a m es F W, S p erli n g M A. Eff ects of ex ercis e tr ai ni n g o n i ns uli n 
1 3 0 7  
s e nsiti vit y i n a d ol esc e nts wit h ty p e I di a b et es. Di a b et es c ar e 1 9 8 5; 8: 4 6 1 -4 6 5  
1 3 0 8  
7.  
Ri d d ell M C, G all e n I W, S m art C E, T a pli n C E, A d olfss o n P, L u m b A N, K o w als ki A, R a b as a -
1 3 0 9  
L h or et R, Mc Cri m m o n RJ, H u m e C, A n n a n F, F o ur ni er P A, Gr a h a m C, B o d e B, G al ass etti P, 
1 3 1 0  
J o n es T W, Mill á n I S, H eis e T, P et ers AL, P etz A, L aff el L M. Ex ercis e m a n a g e m e nt i n ty p e 1 
1 3 1 1  
di a b et es: a c o ns e ns us st at e m e nt. L a nc et Di a b et es E n d ocri n ol  2 0 1 7; 5: 3 7 7 -3 9 0  
1 3 1 2  
8.  
N e y m a n A, W o er n er S, R us s M, Y ar br o u g h A, Di M e gli o L A. Str at e gi es T h at A d ol esc e nts 
1 3 1 3  
Wit h Ty p e 1 Di a b et es Us e i n R el ati o n t o Ex ercis e. Cli n Di a b et es  2 0 2 0; 3 8: 2 6 6 -2 7 2  
1 3 1 4  
9.  
Ek hl as p o ur L, F orl e nz a G P, C h er n a vvs ky D, M a a hs D M, W a d w a R P, D e b o er M D, M ess er 
1 3 1 5  
L H, T o w n M, Pi n n at a J, Kr us e G, K o v atc h ev B P, B ucki n g h a m B A, Br et o n M D. Cl os e d l o o p 
1 3 1 6  
c o ntr ol i n a d ol esc e nts a n d c hil dr e n d uri n g wi nt er s p orts: Us e of t h e T a n d e m C o ntr ol -I Q 
1 3 1 7  
A P s yst e m. P e di atric di a b et es  2 0 1 9;  
1 3 1 8  
1 0.  
Br o w n S A, K o v atc h e v B P, R a g hi n ar u D, L u m J W, B ucki n g h a m B A, K u d v a Y C, L aff el  L M, L e vy 
1 3 1 9  
CJ, Pi ns k er J E, W a d w a R P, D ass a u E, D o yl e FJ, 3r d, A n d ers o n S M, C h urc h M M, D a dl a ni V, 
1 3 2 0  
Ek hl as p o ur  L,  F orl e nz a  G P,  Is g a n aitis  E,  L a m  D W,  K oll m a n  C,  B eck  R W.  Six -M o nt h 
1 3 2 1  
R a n d o miz e d, M ultic e nt er Tri al of Cl os e d -L o o p C o ntr ol i n Ty p e 1 Di a b et es. N E n gl J M e d  
1 3 2 2  
2 0 1 9; 3 8 1: 1 7 0 7 -1 7 1 7  
1 3 2 3  
1 1.  
Br et o n M D, K a n a p k a L G, B eck R W, Ek hl as p o ur L, F orl e nz a G P, C e n giz E, Sc h o el w er M, 
1 3 2 4  
R u e d y KJ, J ost E, C arri a L, E m or y E, Hs u LJ, Oli v eri M, K oll m a n C C, D o kk e n B B, W ei nzi m er 
1 3 2 5  
S A, D e B o er M D, B ucki n g h a m B A, C h er ñ a vvs ky D, W a d w a R P. A  R a n d o miz e d Tri al of 
1 3 2 6  
Cl os e d -L o o p C o ntr ol i n C hil dr e n wit h Ty p e 1 Di a b et es. N E n gl J M e d  2 0 2 0; 3 8 3: 8 3 6 -8 4 5  
1 3 2 7  

CLI NI C AL P R O T O C OL  
 
 
J D R F SI _1 4 -A pr -2 0 2 2 
 
P a g e 6 6  of 6 6  
 
1 2.  
L o p ez  P E,  Ev a ns  M,  Ki n g  B R,  J o n es  T W,  B ell  K,  Mc El d uff  P,  D a vis  E A,  S m art  C E.  A  
1 3 2 8  
r a n d o miz e d c o m p aris o n of t hr e e pr a n di al i ns uli n d osi n g al g orit h ms f or c hil dr e n a n d 
1 3 2 9  
a d ol esc e nts wit h Ty p e 1 di a b et es. Di a b et M e d  2 0 1 8; 3 5: 1 4 4 0 -1 4 4 7  
1 3 3 0  
1 3.  
F a bris C, Oz asl a n B, Br et o n M D. C o nti n u o us Gl uc os e M o nit ors a n d Acti vity Tr ack ers t o 
1 3 3 1  
I nf or m I ns uli n D osi n g i n Ty p e 1 Di a b et es: T h e U ni v ersity of Vir gi ni a C o ntri b uti o n. S e ns ors 
1 3 3 2  
( B as el) 2 0 1 9; 1 9  
1 3 3 3  
1 4.  
Vis e nti n R, C a m p os -N á ñ ez E, Sc hi a v o n M, Lv D, V ett or etti M, Br et o n M, K o v atc h ev B P, 
1 3 3 4  
D all a M a n C, C o b elli C. T h e U V A/ P a d o v a Ty p e 1 Di a b et es Si m ul at or G o es Fr o m Si n gl e M e al 
1 3 3 5  
t o Si n gl e D a y. J o ur n al of di a b et es sci e nc e a n d t ec h n ol o gy 2 0 1 8; 1 2: 2 7 3 -2 8 1  
1 3 3 6  
1 5.  
Br et o n M D, P at e k S D, Lv D, Sc h ertz E, R o bic J, Pi n n at a J, K oll ar L, B ar n ett C, W a k e m a n C, 
1 3 3 7  
Oli v eri M, F a bris C, C h er n a vvs ky D, K o v atc h e v B P, A n d ers o n S M. C o nti n u o us Gl uc os e 
1 3 3 8  
M o nit ori n g a n d I ns uli n I nf or m e d A d vis ory S yst e m wit h A ut o m at e d T itr ati o n a n d D osi n g 
1 3 3 9  
of I ns uli n R e d uc es Gl uc os e V ari a bility i n Ty p e 1 Di a b et es M ellit us. Di a b et es t ec h n ol o gy & 
1 3 4 0  
t h er a p e utics 2 0 1 8; 2 0: 5 3 1 -5 4 0  
1 3 4 1  
1 6.  
F a bris C, N ass R M, Pi n n at a J, C arr K A, K or a vi CL K, B ar n ett CL, Oli v eri M C, A n d ers o n S M, 
1 3 4 2  
C h er n a vvs ky D R, Br et o n M D. T h e Us e of a S m art B ol us C alc ul at or I nf or m e d b y R e al -ti m e 
1 3 4 3  
I ns uli n S e nsiti vit y Ass ess m e nts R e d uc es P ost pr a n di al Hy p o gl yc e mi a F oll o wi n g a n A er o bic 
1 3 4 4  
Ex ercis e S essi o n i n I n di vi d u als Wit h Ty p e 1 Di a b et es. Di a b et es c ar e  2 0 2 0; 4 3: 7 9 9 -8 0 5  
1 3 4 5