A Randomized, Double-Blind, Placebo Controlled Trial of Budesonide for the Treatment of Active Lymphocytic Colitis
Phase: PHASE2
Conditions: Lymphocytic Colitis, Diarrhea
Sponsor: Mayo Clinic

 
 
A Randomized, Double-Blind, Placebo-
Controlled Trial of Budesonide For The 
Treatment Of Active Lymphocytic Colitis 
 
NCT00217022 
 
May 17, 2017 

 
 
 
 
 
 
 
 
A R a n d o mize d, D o u ble -Bli n d, Pl ace b o -C o ntr olle d Tri al of 
B u des o ni de F or T he Tre at me nt Of Acti ve L y m p h oc ytic 
C olitis  
 
 
 
 
 
 
 
 
 
 
 
Pri nci ple I n v esti gat or:  D arrell S. Par di, M D  
 
C oi n vesti gat ors: Willia m J. Sa n d b or n. M D 
Lisa A. B oar d ma n, M D 
Peter W. Carr yer, M D 
J o nat ha n E. Clai n, M D 
La wre n ce J. E g a n, M D  
E d war d V. L oft us, M D 
Ke n net h W. Sc hr oe der, M D 
T h o mas C. S m yr k, M D 
Willia m J. Tre mai ne, M D  
Ala n R. Zi ns miester, P h D 
Patricia P. Ka m mer  
 
 
 
 
Di visi o n of Gastr oe nter ol o g y a n d He pat ol o g y, Ma y o Cli nic a n d 
F o u n dati o n, R oc hester, Mi n nes ota. 
 

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I. A bstr act: 
Micr osc o pic c olitis is a n i ncreasi n gl y dia g n ose d ca use of c hr o nic diarr hea, wit h t w o mai n 
s u bt y pes: c olla ge n o us a n d l y m p h oc ytic c olitis.  U nc o ntr olle d re p orts h a ve s u g geste d t hat 
vari o us dr u gs ca n b e be n eficial i n  treati n g micr os c o pic c olitis, b ut fe w treat me nts ha ve bee n 
e val uate d i n r a n d o mize d c o ntr olle d trials.  T h us, treat me nt is g ui de d m ostl y b y a nec d otal 
re p orts, cas e seri es, a n d p h ysicia ns' e x perie n ce.  I n o ur u nc o ntr olle d e x p erie nce, c ortic ost er oi ds 
are o ne of t he m ost eff ecti ve t hera pies f or micr osc o pic c olitis, b ut are n ot t y picall y use d as a 
first li ne t hera p y beca use of t o xicit y.  B u des o ni de has bee n re p orte d t o be of cli nical be nefit i n 
s mall, u nc o ntr olle d series of patie nts wit h micr osc o pic c olitis, a n d rece nt c o ntr olle d trials 
s h o we d t hat it is s u peri or t o place b o i n c olla ge n o us c olitis.  We pr o p ose a st u d y of b u des o ni de 
i n patie nts wit h t he l y m p h oc ytic t y pe of micr osc o pic c olitis. 
 
II.  B ac k gr o u n d a n d Si g nific a nce: 
Micr osc o pic c olitis is a r elati vel y c o m m o n ca use of c hr o nic w ater y diarr hea.  T he t w o mai n 
t y pes of micr osc o pic c olitis are l y m p h oc ytic a n d c olla ge n o us c olitis.  N u mer o us t hera pies 
ha ve bee n descri be d f or t hese c o n diti o ns ( 1), b ut o nl y bis m ut h s u bsalic ylate ( 2) a n d 
b u des o ni de ( 3, 3a, 3 b) ha ve bee n st u die d i n ra n d o mize d c o ntr olle d trials.  I n t he lar gest 
u nc o ntr olle d series of p atie nts wit h l y m p h oc ytic c olitis ( 4) a n d c olla ge n o us c olitis ( 5), 
c ortic oster oi ds ar e a m o n g t he m ost effecti ve t h era pies wit h res p o nse rates of 7 0 - 8 0 %.  
H o we ver, tra diti o nal c ortic oster oi ds ha ve si g nifica nt s h ort- a n d l o n g- ter m si de effects, 
ca usi n g s o me cli nicia ns t o a v oi d t heir use.  B u des o ni de is a s y nt hetic c ortic oster oi d wit h hi g h 
p ote nc y b ut li mite d s yste mic bi oa vaila bilit y d ue t o hi g h first -pass he patic meta b olis m  ( 6).  
T he c o ntr olle d ileal r elease ( CI R) f or m ulati o n of b u des o ni de a vaila ble i n t h e U S ( E nt oc ort 

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E C) is desi g ne d t o deli ver dr u g ma xi mall y t o t he distal ile u m a n d pr o xi mal c ol o n, c o m pare d 
t o t he B u de n ofal k f or m ul ati o n use d i n t he Baert st u d y ( 3), t hat is desi g ne d t o deli ver dr u g t o 
t he c ol o n ( 6).  T h us, E nt oc ort E C is t he oreticall y less i deal f or a p a nc ol o ni c pr ocess li ke 
micr osc o pic c olitis.  H o we ver, o nl y 5 2- 7 9 % of b u des o ni de is a bs or be d i n t he ile ocecal re gi o n, 
lea vi n g 2 1- 4 8 % of t he dr u g f or deli ver y t o t he c ol o n ( 6).  F urt her m ore, se v eral case re p orts 
ha ve s h o w n efficac y of t he CI R f or m ulati o n i n c olla ge n o us a n d l y m p h oc ytic c olitis ( 5, 7- 9), 
i ncl u di n g pre d nis o ne-r efr act or y cases ( 8), a n d t w o ra n d o mize d trials ha v e s h o w n t he CI R 
f or m ulati o n t o be s u peri or t o place b o i n patie nts wit h c olla ge n o us c olitis ( 3a, 3 b).  T heref ore, 
CI R b u des o ni de ma y als o pr o ve t o be a n effecti ve treat me nt f or l y m p h oc ytic c olitis. 
 
T he c o nce pt of "satisfact or y c o ntr ol" of diarr hea is si milar t o t he "a de q uate relief" e n d p oi nt 
de v el o pe d t o pr o vi de a mea ni n gf ul, patie nt-e val uat e d meas ure of i m pr o ve m e nt i n s u bjects 
wit h diarr hea- pre d o mi na nt I B S ( 1 2). I n a d diti o n, t he dail y n u m ber of st o ols will be use d as a 
q ua ntitati ve meas ure of efficac y.  I n I B S, "a de q u ate relief" c orrelates wit h v ari o us " o bjecti ve" 
meas ures s uc h as pai n se verit y sc ores a n d fre q ue n c y a n d c o nsiste nc y of st o ols ( 1 2).  T his 
c o nce pt is bei n g a d a pte d f or t he pres e nt st u d y t o a d d a s u bjecti ve c o m p o ne nt t o t he patie nt's 
e val uati o n, si nce diarr hea as a s y m pt o m is s u bjecti ve a n d si m pl y s h o wi n g a c ha n ge i n t he 
n u m ber of st o ols per da y ma y n ot reflect t he patie nt's e x perie nce.   
 
Alt h o u g h micr osc o pic c olitis ma y be c o nsi dere d u nc o m m o n b y s o me, it acc o u nts f or 
a p pr o xi matel y 1 0 % of c hr o nic diarr h ea.  I n E ur o p ea n st u dies, its i nci de nce is a p pr o xi matel y 
5. 7/ 1 0 0, 0 0 0 ( 1), a p pr o ac hi n g t hat of Cr o h n's disease ( 1 0) a n d ulcerati ve c olitis ( 1 1).  T he 

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si g nifica nce of t h e pr o p ose d st u d y lies i n t he fact t hat t here are fe w c o ntr olle d trials t o g ui de 
t hera pe utic c h oices i n patie nts wit h l y m p hoc ytic c olitis.  
 
Fecal Lact oferri n A nal ysis:  A variet y of st o ol mar kers ha ve b ee n assesse d as dia g n ostic 
tests t o disti n g uis h patie nts wit h diarr hea d ue t o i nfla m mat or y c o n diti o ns fr o m t h ose wit h 
n o ni nfla m mat or y ca uses.  Lact oferri n is a gl yc o pr otei n c o ntai ne d i n ne utr o p hilic 
sec o n dar y gra n ules t hat is release d i n res p o nse t o ne utr o p hil acti vati o n.  Of se veral 
pr otei ns releas e d b y acti vate d ne utr o p hils, lact oferri n was s h o w n t o be t he m ost sta ble i n 
feces, a n d its release was f o u n d t o be m ost efficie nt ( S ugi, et al. A m J Gastr o 
1 9 9 6; 9 1: 9 2 1).  Fecal lact oferri n is i ncrease d i n p atie nts wit h bacterial ca uses of diarr hea 
w hic h res ult i n i nfla m mati o n c o m pare d t o patie nts wit h diarr hea d u e t o n o ni nfla m mat or y 
bacteria, vir uses, or t h ose i n w hic h n o or ga nis m w as i de ntifie d ( Gree n b er g, et al. J I nfect 
Dis 2 0 0 2; 1 8 5: 9 4 4, McI v er, et al. Pat h ol o g y 2 0 0 1; 3 3: 3 5 3, C h oi. J Cli n Micr o bi ol 
1 9 9 6; 3 4: 2 3 3 7).  I n fact, s o me a ut h ors c o nsi der it as t he scree ni n g test of c h oice f or 
patie nts wit h ac ute diarr h ea t o deter mi ne w h o s h o ul d ha ve st o ol c ult ures perf or me d 
( H uic h o Pe diat I nf ect Dis J 1 9 9 7; 1 6: 6 4 4).  Fecal lact oferri n has bee n s h o w n t o be as 
usef ul as fecal occ ult bl o o d testi n g i n detecti n g vari o us c ol orectal diseases ( Sait o h I nter n 
Me d 2 0 0 0; 3 9: 7 7 8). 
 
Fecal lact of erri n has b ee n st u die d fairl y e xte nsi vel y i n i nfla m mat or y b o wel disease a n d 
has bee n s h o w n t o be a s e nsiti ve a n d s pecific m ar ker of acti ve I B D c o m p are d t o irrita ble 
b o wel s y n dr o me a n d h ealt h y c o ntr ols ( Ka ne, et al. Gastr oe nter ol o g y 2 0 0 1; 1 2 0: A 2 7 6, 
B u der us, et al. Gastr o e nter ol o g y 2 0 0 2; 1 2 2: A 2 1 9 # 1, Fi ne. A m J Gastr o 1 9 9 8; 9 3: 1 3 0 0).  

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I n p atie nts wit h I B D, t h e le vels of fecal lact oferri n c orrel ate wit h disease acti vit y ( B o o ne, 
et al. Gastr oe nt er ol o g y 2 0 0 0; 1 1 8: A 1 1 1 8, B u der us, et al. Gastr oe nt er ol o g y 2 0 0 2; 1 2 2: A 2 1 9 
# 1), a n d i n i n di vi d ual patie nts, t he le vel of lact oferri n decreases w h e n re missi o n is 
i n d uce d ( B u der us, et al. Gastr oe nter ol o g y 2 0 0 2; 1 2 2: A 2 1 9 # 2). 
 
T here is o nl y o ne r e p ort i n t he literat ure w h ere fecal lact oferri n le vels were st u die d i n 
micr osc o pic c olitis ( Fi ne et al. A m J Gastr o 1 9 9 8; 9 3: 1 3 0 0).  I n t his s mall st u d y, 8 % of 
patie nts wit h micr osc o pic c olitis ha d ele vate d fecal lact oferri n le vels.  
 
H L A Ass ociati o ns:  O ne st u d y of H L A ha pl ot y pes s h o we d a n i ncreas e i n A 1 a n d D R W 5 3 
i n l y m p h oc ytic c olitis a n d a decr eas e i n D Q 2 i n c olla ge n o us c olitis ( 1 3).  H o we ver, t his 
sa me gr o u p later re p ort e d i ncreas e d A 1 a n d d ecrease d i n A 3 i n l y m p h oc ytic c olitis a n d n o 
H L A ass ociati o ns i n c oll a ge n o us c olitis ( 1 4).  Fi n e a n d c ollea g ues s h o we d a n i ncrease i n 
D Q 2 a n d D Q 1, 3 i n l y m p h oc ytic c olitis a n d c olla g e n o us c olitis, si milar t o t he patter n see n 
i n celiac s pr u e ( 1 5).  Ot h ers ha ve f o u n d n o H L A ass ociati o ns ( 1 6).  A b n or mal H L A D R 
e x pressi o n o n c ol o nic e pit helial cells has bee n d es cri be d, s u g gesti n g t hat M H C- restricte d 
i m m u ne acti vati o n c o ul d be i n v ol ve d i n t he pat h o g e nesis of micr osc o pic c olitis ( 1 7, 1 8).  
Gi ve n t he discre p a nt fi n di n gs, h o we ver, it is diffic ult t o dra w c o ncl usi o ns a b o ut H L A 
ass ociati o ns i n micr osc o pic c olitis.  
 
III.  H y p ot heses: 
1)  B u des o ni de will be safe a n d eff ecti ve c o m pare d wit h place b o f or t h e treat me nt of diarr hea 
i n l y m p h oc ytic c olitis. 

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2)  Fecal lact of erri n le v els will c orrelate wit h s y m pt o ms a n d hist ol o gic disease acti vit y i n 
patie nts wit h l y m p h oc ytic c olitis.  
 
I V. S pecific Ai ms: 
1) T o c o m par e efficac y of b u des o ni de a n d place b o i n l y m p h oc ytic c olitis i n pr o vi di n g relief 
of diarr hea ( pri mar y e n d p oi nt) as well as i n i m pr o vi n g fre q ue n c y, c o nsiste nc y, a n d ur ge nc y of 
diarr hea a n d de gree of i nfla m mati o n o n c ol o n bi o psies (sec o n dar y e n d p oi nts). 
2) T o c o m par e t he saf et y a n d t olera bilit y of b u des o ni de c o m pare d t o place b o i n patie nts wit h 
l y m p h oc ytic c olitis (sec o n dar y e n d p oi nt). 
3) T o assess t he c orrel ati o n bet wee n fecal lact oferri n c o nce ntrati o ns a n d s y m pt o ms a n d 
de gree of i nfla m mati o n o n m uc osal bi o psies i n patie nts wit h l y m p h oc ytic c oliti s. 
3)  T o c har acteri ze H L A t y pi n g i n patie nts wit h l y m p h oc ytic c olitis.  
 
V.  Preli mi n ar y st u dies:   T he t hera p e utic p ote ntial of b u des o ni de f or t he treat me nt of 
l y m p h oc ytic c olitis is disc usse d a b o ve.  Fr o m 1 9 9 7- 1 9 9 9, i ncl usi ve, a p pr o xi matel y 2 0 0 
patie nts wit h l y m p h oc ytic c olitis a n d 2 0 0 wit h c olla ge n o us c olitis were e val uate d at Ma y o, or 
1 3 3 patie nts per year wit h eit her c o n diti o n.  We h a ve pre vi o usl y re p orte d o ur e x peri e nce wit h 
t hera p y i n patie nts wit h l y m p h oc ytic c olitis ( 4).  I n a d diti o n, o ur gr o u p has e xte nsi ve 
e x perie n ce wit h cli nical trials i n patie nts wit h i nfla m mat or y b o wel disease.  
 
VI.  Rese arc h Desi g n a n d Met h o ds:  
        A. St u d y desi g n: We pr o p ose a pr os pecti ve, ra n d o mize d, d o u ble bli n d, place b o-
c o ntr olle d trial of b u des o ni de f or t he treat me nt of l y m p h oc ytic c olitis.   

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B. Recr uit me nt:  P ote ntiall y eli gi ble s u bjects will be i de ntifie d at Ma y o R oc hester i n 
se veral w a ys.  First, r ece ntl y dia g n ose d cases will be i de ntifie d b y dail y re vie w of t he 
dia g n oses ma de i n t he D e part me nt of Pat h ol o g y.  Sec o n d, t h e GI a p p oi nt me nt office at t he 
Ma y o Cli nic will i de ntif y s u bjects referre d wit h a dia g n osis of l y m p h oc ytic c olitis.  T hir d, 
patie nts w h o ha ve bee n dia g n ose d wit hi n t he last t hree years at M a y o will be c o ntact e d b y 
letter ( A p pe n di x 1) a n d i nf or me d of t he st u d y.  As n ote d a b o ve, a p pr o xi matel y 1 3 3 patie nts 
wit h micr osc o pic c olitis are see n eac h year at M a y o, a n d a p pr o xi matel y 4 0 0 were s ee n i n t he 
last t hree years, gi vi n g a p o ol of o ver 5 0 0 s u bjects wit h micr osc o pic c olitis.  A p pr o xi matel y 
half of t hese will ha ve l y m p h oc ytic c olitis, lea vi n g ~ 2 5 0 p ote ntial s u bjects f or e nr oll me nt.  
We will recr uit s u bjects u ntil we e nr oll 3 0 wit h l y m p h oc ytic c olitis.  
 
C. I ncl usi o n Criteria: 
1.  A ge ≥ 1 8 years of a g e.  
2.  Diarr hea, defi n e d as  a mi ni m u m of 3 b o wel m o ve me nts per da y a n d greater t ha n “ mil d” 
(see bel o w), c urre ntl y o n n o treat me nt or acti ve des pite treat me nt. 
3.  L y m p h oc ytic c olitis c o nfir me d hist ol o gicall y b y t he st u d y pat h ol o gist ( T C S) o n left si de d 
c ol o n bi o psies.  If bi o psies are n ot a vaila ble wit hi n o ne year of st u d y e ntr y, re peat fle xi ble 
si g m oi d osc o p y wit h left si de d bi o psies ( 2 si g m oi d, 2 desce n di n g) will be p erf or me d.  
 
D. E xcl usi o n Criteria:  
1. Pre vi o us u ns uccessf ul treat me nt wit h c ortic oster oi ds or i m m u n os u p pressi ve dr u gs. 
2. Hist or y of se ver e c orti c oster oi d si de effects. 

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3. C ortic oster oi d, ticl o pi di ne, or fl uta mi de use wit hi n t he pre vi o us 4 wee ks. 
4. A nti bi otic, mesala mi ne or bis m ut h s u bsalic ylate use wit hi n t w o wee ks.  
5. C urre nt use of a ntic h oli ner gics, c h olest yra mi ne, narc otics, ket o c o naz ol e, itrac o naz ol e, 
rit o na vir, i n di na vir, sa q ui na vir, er yt hr o m yci n, or gra pefr uit j uice. 
6. K n o w n acti ve me di cal c o n diti o ns, i ncl u di n g ca ncer, i nfecti o n, u nc o ntr olle d h y perte nsi o n or 
dia betes, oste o p or osis, pe ptic ulcer diseas e, gla uc o ma, cataracts, li ver cirr h osis or hist or y of 
t u berc ul osis. 
7. Ot her diarr heal c o n diti o ns (s pr ue, i nfecti o n, h y pert h yr oi dis m, lact ose i nt olera nce). 
8. Pre g na nt or n ursi n g f e males. 
9. Patie nts wit h o ut a tele p h o ne or u na ble t o c o m m u nicate i n E n glis h o ver t he tele p h o ne, or 
u na ble or u n willi n g t o gi ve c o nse nt. 
1 0. K n o w n h y perse nsiti vit y t o or i nt olera nce of b u des o ni de. 
 
E. Met h o ds: Patie nts wit h bi o ps y- pr o ve n l y m p h oc ytic c olitis will c o m plete a s y m pt o m 
q uesti o n naire ( A p p e n di x 2).  T here will be a o ne- wee k peri o d of o bser v ati o n pri or t o st u d y 
e ntr y t o i ns ure s uffici e ntl y si g nifica nt diarr hea.  All dr u gs use d t o treat c olitis will be 
disc o nti n ue d f or t he a p pr o priate ti me peri o d (s ee e xcl usi o n criteria a b o v e) pri or t o t he start of 
t his o bser vati o n peri o d.  L o pera mi de will be st o p pe d at least t w o da ys pri or t o t he o bser vati o n 
peri o d.   
D uri n g t he o ne- w ee k o bs er vati o n peri o d, s u bjects will ma ke a dail y rec or d of t he 
n u m ber of b o wel m o ve m e nts a n d s u bjecti vel y sc ore t heir diarr hea as " n o ne" ( 0), " mil d" ( 1), 
" m o derate" ( 2), or "se ver e" ( 3).  T o q ualif y f or t he st u d y, t he mea n n u m ber of dail y b o wel 
m o ve me nts m ust be > 4, a n d t he mea n diarr hea sc ore m ust be > 1.   

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After e ns uri n g s ufficie ntl y se vere di arr h ea f or partici pati o n, a st o ol sa m ple will be 
c ollecte d f or meas ur e me nt of t he fecal lact oferri n le vel (see b el o w) . O n ce d uri n g t he st u d y 
bl o o d will be dra w n f or H L A t y pi n g (see b el o w).  W o me n of c hil d beari n g p ote ntial will ha ve 
a ser u m pre g n a nc y test p erf or me d.  T hirt y s u bjects wit h l y m p h oc ytic c olitis will be 
ra n d o mize d e q u all y ( 1: 1) b y t he use of ra n d o m- or dere d, seale d, o pa q u e e n vel o pes t o 
b u des o ni de 9 m g/ d or a place b o.  T he st u d y dr u g will be ta ke n dail y f or 8 wee ks. 
 
T he st u d y assista nt will m o nit or s u bjects b y tele p h o ne wee kl y f or c o m plia nce, 
efficac y, a n d si de eff ects.  L o pera mi de will be all o we d as "res c ue" t h era p y f or > 7 b o wel 
m o ve me nts per da y, a n d t he n u m ber of ta blets ta k e n will be rec or de d a n d use d as a sec o n dar y 
o utc o me meas ur e.  
 
Fecal lact of erri n a n al ysis:  We will use t he I B D -S C A N q ua ntitati ve lact oferri n E LI S A 
test pr o vi de d b y Tec h L a b, Blac ks b ur g, Vir gi nia.  A sta n dar d c ur ve is ge n erate d usi n g p urifie d 
h u ma n lact oferri n.  Patie nt fecal s peci me ns are dil ute d seriall y 1: 1 0, a n d t h e dil uti o n gi vi n g a n 
o ptical de nsit y o n t he li near part of t he c ur ve is us e d t o deter mi ne lact oferri n c o nce ntrati o n. 
 
F. Safet y M o nit ori n g: I n pri or st u dies, b u des o ni de treat me nt f or 8 w ee ks h as bee n 
e xtre mel y saf e, wit h a n a d verse e v e nt pr ofile si milar t o place b o.  T h us, we are pr o p osi n g t o d o 
t his st u d y wit h o ut a Dr u g Safet y M o nit ori n g B oar d.  I n a d diti o n, we d o n ot pla n o n ha vi n g 
st o p pi n g r ules i n place f or t o xicit y.  We will m o nit or f or a n y a d vers e e ve nts i n st u d y patie nts, 
a n d we will m o nit or f or l ac k of efficac y.  As me nti o ne d a b o ve, l o pera mi de will be all o we d f or 
t h ose patie nts w h o ha ve > 7 b o wel m o ve me nts per da y.  If t he di arr h ea d oes n ot res p o n d t o t his 

1 0 
s y m pt o matic treat me nt, t he patie nt will be wit h dra w n fr o m t he st u d y, c o u nt e d as a treat me nt 
fail ure, a n d pr o vi de d o pe n-la bel treat me nt at t he directi o n of o ne of t h e st u d y p h ysicia ns or t heir 
re g ular p h ysicia n. 
 
G. F oll o w- u p a n d E n d p oi nt Ascertai n me nt: Eac h p atie nt will rec or d t he c o nsiste nc y a n d 
fre q ue n c y of st o ols, ur ge nc y, a b d o mi nal disc o mf ort, a n d a n y ot her s y m pt o ms dail y ( A p pe n di x 
3).  At eac h wee kl y tel e p h o ne f oll o w- u p, t he pri m ar y e n d p oi nt of "satisfact or y c o ntr ol of 
diarr hea" will be assesse d.  After 8 w ee ks of treat me nt, t he st u d y dr u g will be st o p pe d a n d a 
ret ur n offi ce visit will occ ur.  Re peat fle xi ble si g m oi d osc o p y wit h left si de d c ol o n bi o psies ( 2 
si g m oi d, 2 desce n di n g) will be o btai ne d wit hi n 7 da ys.  A bli n de d pat h ol o gist ( T C S) will 
c o m pare t hes e bi o psies t o pretreat me nt bi o psies acc or di n g t o t he para meters liste d i n A p pe n di x 
4.  Res p o n ders will be f oll o we d wee kl y f or a n ot her f o ur w ee ks f or rec urre n ce, defi n e d as > 4 
st o ols per da y or a st o ol c o nsiste nc y sc ore of 4 or 5 ( A p pe n di x 3). 
 
H. A ntici pate d Res ults:  We a ntici pate t h at b u des o ni de will be s u peri or t o place b o 
wit h o ut i ncrease d si de effects.  
 
I. Data A n al ysis:  T he pri mar y a nal ysis will c o m pare t he pr o p orti o n of pati e nts i n eac h 
treat me nt gr o u p wit h satisfact or y c o ntr ol of diarr h ea d uri n g at least t hree of t he last f o ur wee ks 
of t he st u d y ( pri mar y e n d p oi nt). A t w o- sa m ple z-s c ore test f or pr o p orti o ns will be use d t o test 
w het her t he "r elief r ates" are diff er e nt bet wee n t he gr o u ps. Sec o n dar y a nal yses will c o m pare  t he 
t w o treat me nt gr o u ps o n: 1) res p o nse, d efi ne d as 5 0 % decrease i n n u m ber of st o ols per da y 
( mea n pr e-treat me nt wee k vs. mea n d uri n g wee k 8 of treat me nt); 2) t h e pr o p orti o n ( per patie nt) 
of t otal st u d y da ys wit h o ut diarr hea; 3) t h e pr o p orti o ns of patie n ts e x perie n ci n g "i m pr o ve me nt" 

1 1 
i n st o ol c o nsiste nc y, ur ge nc y a n d a b d o mi nal pai n b y at least o ne p oi nt ( o n t he scale us e d i n 
A p pe n di x 3).  T hes e res ults will be c o m pare d usi n g a t w o-sa m ple test f or pr o p orti o ns.  Fi nall y, 
hist ol o gic i m pr o ve me nt c o m pare d t o ba seli ne bi o psies will be assesse d ( A p pe n di x 4) as well as 
si de effects a n d ti me (i n da ys) t o rec urre n ce of diarr hea after disc o nti n uati o n of st u d y dr u g. 
 
Alter nati ve a n al yses f or t he pri mar y a n d s ec o n dar y e n d p oi nts will be base d o n ge neralize d 
re gressi o n m o dels i nc or p orati n g p ote ntiall y i m p orta nt c o variates (e. g. a g e, ge n der, s u bt y pe of 
c olitis) al o n g wit h treat me nt gr o u p as pre dict ors of res p o nse.  F or e x a m ple, a l o gistic re gressi o n 
a nal ysis of satisfact or y c o ntr ol of diarr hea ( Y es, N o) as t he bi nar y d e pe n de nt varia ble will be 
e xa mi ne d, a n d t he o d ds r ati o ( 9 5 % CI) f or relief (treate d: n ot treate d) esti mate d usi n g t he 
re gressi o n c o effi cie nt fr o m t he m o del.  A d diti o nal s u m maries of patie nt c h aract eristics, 
hist ol o g y, a n d si de effects will be ge nerat e d f or eac h treat me nt gr o u p. 
 
Fecal lact of erri n le v els will be c o m pare d wit h t he de gree of diarr hea a n d hist ol o g y ( A p pe n di x 
4) at baseli ne a n d at wee k 8.  H L A t y pe distri b uti o n will be descri be d. 
 
Data will be a n al yze d usi n g a n "i nte nti o n- t o-treat" met h o d ol o g y, a n d dr o p- o uts will be c o u nte d 
as fail ures.  
 
J. Sa m ple Size Assess me nt:  
Base d o n u nc o ntr olle d data, t he res p o nse t o ster oi ds i n micr osc o pic c olitis is a p pr o xi matel y 7 0-
8 0 % ( 4, 5).  T he a vera ge res p o nse t o b u des o ni de i n t he ra n d o mize d tri als i n c olla ge n o us c olitis 
was 7 7 %, w hile t he b est res p o nse t o place b o was 2 1 %.  At a n al p ha of 0. 0 5 a n d usi n g a t w o-

1 2 
si de d test, 1 5 patie nts will be nee de d i n t he treat m e nt gr o u p a n d 1 5 i n t he place b o gr o u p t o ha v e 
8 0 % p o wer t o det ect a si milar differe nce i n o ur st u d y of patie nts wi t h l y m p h oc ytic c olitis.  
T h us, t he t otal sa m ple size will be 3 0 s u bjects.    
 
Ti m et a ble:  
If t he n u m ber of s u bjects see n at Ma y o re mai ns sta ble, we w o ul d e x pect t o see 6 5 patie nts eac h 
year wit h l y m p h oc ytic c olitis.  We ha ve n o data o n h o w ma n y w o ul d satisf y t he i ncl usi o n a n d 
e xcl usi o n criteria.  We will atte m pt t o i ncrease e nr oll me nt b y c o ntacti n g patie nts see n i n t he last 
t hree years at Ma y o, i nf or mi n g t he m b y mail of t he st u d y a n d i n viti n g t heir partici pati o n 
( A p pe n di x 1).  We a ntici pate e nr olli n g 3- 5 s u bjects per m o nt h, or 3 0 s u bjects i n 6- 9 m o nt hs, 
a n d c o m pleti n g t he st u d y wit hi n 1 2 m o nt hs. 
 
VII.  H u m a n S u bjects : 
1.  P o p ulati o n: A d ults ≥ 1 8 years ol d wit h acti ve l y m p h oc ytic c olitis.   
2.  Researc h m aterials: St u d y data will i ncl u de de m o gra p hics, s y m pt o ms, c ol o n bi o psies, 
st o ol f or lact oferri n a nal ysis a n d bl o o d f or H L A t y pi n g. 
3.  Recr uit me nt: Patie nts will be i de ntifie d at Ma y o t hr o u g h t he De p art me nt of Pat h ol o g y a n d 
t he Di visi o n of Gastr oe nt er ol o g y a n d H e pat ol o g y.  I n a d diti o n, patie nts see n wit hi n t he 
past t hree years at Ma y o will be c o ntacte d b y mail ( A p pe n di x 1). 
4.  P ote ntial ris k/ pr otecti o n: B u des o ni de has a ver y fa v ora ble s afet y pr ofile, wit h si de effects 
c o m para ble t o place b o ( p ac ka g e i nsert).  It is F D A a p pr o ve d f or use i n Cr o h n’s disease.  
Fle xi ble si g m oi d osc o p y wit h m uc osal bi o ps y is a ver y safe pr oce d ure, wit h < 1 % ris k of 
seri o us a d vers e e v e nts.  T he mai n ris ks will be disc o mf ort relat e d t o t he use of e ne m as a n d 

1 3 
of t he pr oce d ure itself.  Alt h o u g h b u des o ni de was s u peri or t o place b o i n pri or st u dies i n 
c olla ge n o us c olitis ( 3, 3a, 3 b), it has n ot bee n st u die d i n l y m p h oc ytic c olitis.  I n a d diti o n, a 
si g nifica nt rate of s p o nta ne o us re missi o n has bee n re p orte d i n micr os c o pic c olitis ( 1).  
F urt her m ore, w e will all o w t he use of l o pera mi de f or brea kt hr o u g h diarr h ea.  T h us, a 
place b o c o ntr ol ar m is j ustifie d a n d et hical.  
5.  Be nefits: T he a vera ge b e nefit of b u des o ni de i n c olla ge n o us c o litis was 7 7 % i n c o ntr olle d 
st u dies ( 3, 3a, 3 b).  Si milar be nefit is e x pecte d i n t h ose wit h l y m p h oc ytic c olitis.  N o 
be nefit is e x pecte d f or t h ose s u bjects ra n d o mize d t o place b o.  Re m u nerati o n will n ot be 
offer e d.  C osts relate d s olel y t o t he st u d y (st u d y me dicati o n, f oll o w u p si g m oi d osc o p y a n d 
bi o ps y) will be pai d f or b y t he st u d y b u d get. 
 
VI.  Ge n der/ Mi n orit y Mi x:  
I n m ost r e p orts, c olla ge n o us c olitis occ urs mai nl y i n fe males w hereas l y m p h oc ytic c olitis has 
a m ore e v e n ge n der distri b uti o n.  T here are n o dat a o n raci al distri b uti o n, b ut m ost re p orte d 
cases are Ca u casia ns.  We will e nr oll s u bjects of eit her ge n der a n d a n y race.  

1 4 
A p pe n di x 1.   Recr uit me nt Letter  
Dear                                  ,  
 
M y c ollea g ues a n d I ar e perf or mi n g a researc h st u d y of a ne w m e dicati o n f or t he 
treat me nt of l y m p h oc ytic c olitis.  Acc or di n g t o o ur rec or ds, y o u ha ve b ee n dia g n ose d wit h 
t his c o n diti o n i n t he past.  If y o ur diarr hea is still si g nifica nt, y o u mi g ht q ualif y t o e nr oll i n 
t his st u d y.  If y o u are i ntereste d or h a ve a n y q uesti o ns, please c o ntact (st u d y assista nt) at 
. 
 
Y o ur decisi o n t o ta ke p art i n t his st u d y is e ntirel y v ol u ntar y.  C urre nt or f ut ure me dical 
care at t he Ma y o Cli nic will n ot be affecte d b y y o ur decisi o n. 
 
Si ncerel y,  
 
 
Darr ell S. Par di, M D  

1 5 
 A p pe n di x 2.   I nitial s y m pt o m q uesti o n naire. 
Na me _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _    M C N _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
1) H o w w o ul d y o u rat e y o ur diarr hea? 
 
  
    
0  
  
1  
  
2  
  
3 
  
        N o ne  
        Mil d   
      M o derate           Se vere  
 
 
2) W hat is t he c o nsiste nc y of y o ur st o ols us uall y? 
 
  
  
1  
  
2  
  
3  
  
4  
  
5 
  
     Ver y har d           Har d   
      F or me d   
        L o ose  
       Water y  
 
 
3) H o w se vere is y o ur a b d o mi nal pai n us uall y? 
 
  
  
0  
  
1  
  
2  
  
3 
  
        N o ne  
         Mil d   
     M o derate          Se vere  
 
4) I n t he last year, ha v e y o u ha d a b d o mi nal pai n f or at least 1 2 wee ks?   Y es / N o 
 
5) Is t he pai n r elie ve d b y a b o wel m o ve me nt?   Yes / N o 
 
6) Is t he pai n ass o ciate d wit h y o ur diarr hea?   Y es / N o 
 
7) Is t he pai n ass o ciate d wit h a c ha n ge i n st o ol f or m (a p peara nce)?  Yes / N o  
 
8) Are y o ur b o wel m o ve me nts us uall y ass ociate d wit h ur ge nc y?  Yes / N o 
 
9) H o w ma n y b o w el m o ve me nts d o y o u ha ve o n a us ual da y?  _ _ _ _ _ 
1 0) Is y o ur diarr hea c o nsta nt or i nter mitte nt? 
1 1) Ha ve y o u l ost a n y w ei g ht?  Yes / N o         If y es, h o w m uc h?  _ _ _ _ _ _ p o u n ds 
1 2) D o y o u use as piri n or ot her art hritis/ pai n me dicati o ns at least t hree da ys per wee k? 
1 3) If yes, w hi c h dr u g a n d w hat d ose? _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
1 4)  D o y o u s m o ke?  Y es / N o      If Yes, h o w m u c h per da y?  _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
1 5)  If n o, di d y o u s m o ke i n t he past? Yes/ N o    If Yes, h o w m uc h per da y? _ _ _ _ _ _ _ _ _ _ _

1 6 
A p pe n di x 3.    
Dail y S y m pt o m Q uesti o n naire   
  
T o da y's Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
1) H o w w o ul d y o u rat e y o ur diarr hea i n t he last 2 4 h o urs? 
 
  
    
0  
  
1  
  
2  
  
3 
  
        N o ne  
        Mil d   
      M o derate           Se vere  
 
 
 
2) W hat was t h e c o nsiste nc y of y o ur st o ols i n t he last 2 4 h o urs? 
 
  
  
1  
  
2  
  
3  
  
4  
  
5 
  
     Ver y har d           Har d   
      F or me d   
        L o ose  
       Water y  
 
 
 
3) H o w se vere w as y o ur a b d o mi nal pai n i n t he last 2 4 h o urs? 
 
  
  
0  
  
1  
  
2  
  
3  
  
4 
  
        N o ne  
         Mil d   
     M o derate          I nte ns e  
       Se vere  
 
 
 
4) Wer e y o ur b o w el m o ve me nts yester da y ass ociate d wit h ur ge nc y?  Yes / N o 
 
 
5) H o w ma n y b o w el m o ve me nts di d y o u ha ve yest er da y?  _ _ _ _ _ _ _ _ _ _ _ 
 
6)  H o w ma n y l o per a mi de/I m o di u m di d y o u use y ester da y ?  _ _ _ _ _ _ _ _ _ _ _ 
 
Wee kl y St u d y c o or di nat or i nter vie w q uesti o n naire: 
"I n t he p ast se ve n d a ys, ha ve y o u ha d s atisfact or y c o ntr ol of y o ur diarr hea?" 
"I n t he p ast se ve n d a ys, ha ve y o u ha d s atisfact or y c o ntr ol of y o ur a b d o mi nal pai n?"  
" Ha ve y o u ha d a n y si de effects fr o m t he st u d y me dicati o n?" 
" Ha ve y o u ha d a n y ne w s y m pt o ms?" 
" D o y o u ha ve a n y q u esti o ns?" 

A p pe n di x 4.   Hist o pat h ol o g y Sc ori n g S yste m 
 
I T E M/ S C O R E  
  
  
0  
  
  
1  
  
  
2 _ _ _ _ _  
  
  
    3 _ _ _ _ _ _ _ _ _  
E pit helial c ha n ges   
  
         N o ne  
  
         Mil d   
  
         M o derate   
  
 
Se vere  
La mi na pr o pria cell ularit y   
       N or mal         
Mil dl y i ncrease d            M o deratel y i ncreas e d   
   De nsel y i ncrease d  
I ntr ae pit helial l y m p h oc yt es        N or mal   
           Mil dl y i ncrease d   
   M o deratel y i ncr eas e d   
   Se verel y i ncrease d  
 
Ma xi m u m sc ore = 9, mi ni m u m = 0  

Refere nces:  
1.  Par di D S, S m yr k T C, Tre mai ne WJ, Sa n d b or n WJ.  Micr osc o pic c olitis: A re vie w.  A m J 
Gastr oe nter ol 2 0 0 2; 9 7: 7 9 4- 8 0 2. 
2. Fi ne K, O g u nji F, Lee E, Laf o n G, T a nzi M.  Ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d 
trial of bis m ut h s u bsalic ylate f or micr os c o pic c olitis.  Gastr oe nter ol o g y 1 9 9 9; 1 1 6: A 8 8 0. 
3. Baert F, Sc h mit A, D' Hae ns G, et al.  B u des o ni de i n c olla ge n o us c olitis: a d o u ble- bli n d 
place b o -c o ntr olle d trial wit h hist ol o gic f oll o w - u p.  Gastr oe nter ol o g y 2 0 0 2; 1 2 2: 2 0- 2 5. 
3a. B o n der u p O K, H a nse n J B, Bir ket- S mit h L, Vester gaar d V, Te gl bjaer g P S, Falli n g b or g 
J.  B u des o ni de treat me nt of c olla ge n o us c olitis: a ra n d o mize d, d o u ble bli n d, place b o 
c o ntr olle d trial wit h m or p h o metric a nal ysis.  G ut 2 0 0 3; 5 2: 2 4 8- 5 1. 
3 b. Mie hl ke S, He y mer P, Bet h ke B, et al.  B u des o ni de treat me nt f or c olla g e n o us c olitis: a 
ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, m ultice nter trial.  Gastr o e nter ol o g y 
2 0 0 2; 1 2 3: 9 7 8- 8 4. 
4. Par di D S, Ra m nat h V R, L oft us E V Jr, Tre mai n e WJ, Sa n d b or n WJ.  L y m p h oc ytic 
C olitis: Cli nical Feat ures, Treat me nt, a n d O utc o m es.  Ma n uscri pt s u b mitte d.  
5. B o hr J, T ys k C, Eri kss o n S, et al.  C olla ge n o us c olitis: a retr os pecti ve st u d y of cli nical 
prese ntati o n a n d tr eat me nt i n 1 6 3 patie nts.  G ut 1 9 9 6; 3 9: 8 4 6- 5 1. 
6. Gree n b er g G R.  Or al b u des o ni de.  Cli n Pers pect Gastr oe nter ol 2 0 0 2: 9- 1 2. 
7. Delari ve J, Sara ga E, D orta G, Bl u m A.  B u des o ni de i n t he treat me nt of c olla ge n o us 
c olitis.  Di gesti o n 1 9 9 8; 5 9: 3 6 4- 6. 
8. La n yi B, Dries V, Die nes H P, Kr uis W.  T hera p y of pre d nis o ne-refract or y c olla ge n o us 
c olitis wit h b u des o ni de.  I nt J C ol orect Dis 1 9 9 9; 1 4: 5 8- 6 1. 

1 9 
9. Va n G oss u m A, Sc h mit A, Pe n y M- O.  Oral b u d es o ni de f or l y m p h oc ytic c olitis.  A m J 
Gastr oe nter ol 1 9 9 8; 9 3: 2 7 0. 
1 0. L oft us E V Jr, Sil verstei n M D, Sa n d b or n WJ, Tre mai ne WJ, Har mse n W S, Zi ns meister 
A R.  Cr o h n's disease i n Ol mste d C o u nt y, Mi n nes ota, 1 9 4 0- 1 9 9 3: I nci de n ce, pre val e nce, 
a n d s ur vi val.  Gastr o e nter ol o g y 1 9 9 8; 1 1 4: 1 1 6 1- 8. 
1 1. L oft us E V Jr, Sil verstei n M D, Sa n d b or n WJ, Tre mai ne WJ, Har mse n W S, Zi ns meister 
A R.  Ulcerati ve c olitis i n Ol mste d C o u nt y, Mi n nes ota, 1 9 7 0- 1 9 9 3: I nci de n ce, pre v ale nce 
a n d s ur vi val.  G ut 2 0 0 0; 4 6: 3 3 6- 4 3. 
1 2. Ca milleri M, N ort hc utt A R, K o n g S, D u kes G E, Mc S orle y D, Ma n gel A W.   Efficac y 
a n d safet y of al osetr o n i n w o me n wit h irrita ble b o wel s y n dr o me: a ra n d o mise d, place b o-
c o ntr olle d trial.  La ncet 2 0 0 0; 3 5 5: 1 0 3 5- 4 0. 
1 3. Giar diell o F M, Laze n b y AJ, Ba yless T M, et al.  L y m p h oc ytic ( micr osc o pic) c olitis.  
Cli nic o pat h ol o gic st u d y of 1 8 patie nts a n d c o m paris o n t o c olla ge n o us c olitis.  Di g Dis Sci 
1 9 8 9; 3 4: 1 7 3 0- 8. 
1 4. Giar diell o F M, Laze n b y AJ, Yar dle y J H, et al.  I n crease d H L A A 1 a n d di mi nis he d H L A 
A 3 i n l y m p h oc ytic c olitis c o m pare d t o c o ntr ols a n d patie nts wit h c olla ge n o us c olitis.  Di g 
Dis Sci 1 9 9 2; 3 7: 4 9 6- 9. 
1 5. Fi ne K D, D o K , Sc h ulte K, et al.  Hi g h pre v ale nce of celiac s pr u e-li ke H L A-D Q g e nes 
a n d e nter o p at h y i n patie nts wit h t he micr osc o pic c olitis s y n dr o me.  A m J Gastr oe nter ol 
2 0 0 0; 9 5: 1 9 7 4- 8 2. 
1 6. S yl westr o wicz T, K ell y J K, H wa n g, W S, et al.  C olla ge n o us c olitis a n d micr osc o pic 
c olitis: t he water y diarr h ea -c olitis s y n dr o me.  A m J Gastr oe nter ol 1 9 8 9; 8 4: 7 6 3- 8. 

2 0 
1 7. M os nier J F, Lar v ol L, Bar ge J, et al.  L y m p h o c ytic a n d c olla ge n o us c olitis: a n 
i m m u n o hist oc he mical st u d y.  A m J Gastr oe nter ol 1 9 9 6; 9 1: 7 0 9- 1 3. 
1 8. Bea u gerie L, L u b oi ns ki J, Br o usse N, et al.  Dr u g i n d uce d l y m p h oc ytic c olitis.  G ut 
1 9 9 4; 3 5: 4 2 6- 8. 

2 1 
TI T L E:   A R a n d o mize d Pl ace b o C o ntr olle d Tri al of B u des o ni de i n Ly m p h ocytic 
C olitis 
 
I N V E S TI G A T O R:  Dr. D. Par di a n d C ollea g ues 
 
A P P R O V E D B Y I N S TI T U TI O N A L R E VI E W B O A R D:  
 
 
T his is a n i m p ort a nt f or m.  Ple ase re a d it c aref ull y.  It tells y o u w h at y o u 
nee d t o k n o w a b o ut t his st u d y.  If y o u a gree t o t a ke p art i n t his rese arc h 
st u d y, y o u nee d t o si g n t his f or m.  Y o ur si g n at ure me a ns t h at y o u h a ve 
bee n t ol d a b o ut t he st u d y a n d w h at t he  ris ks are.  Y o ur si g n at ure o n t his 
f or m als o me a ns t h at y o u w a nt t o t a ke p art i n t his st u d y. 
 
 
 
W h y is t his st u d y bei n g d o ne ?  
 
T his st u d y is bei n g d o n e t o fi n d o ut w hat effects ( g o o d a n d ba d) b u des o ni de has o n 
y o u a n d o n t he diarr hea a n d ot her s y m pt o ms y o u ha ve fr o m y o ur l y m p h oc ytic 
c olitis (als o k n o w n as micr osc o pic c olitis).  B u des o ni de is a me dicati o n t hat 
decreases i nfla m mati o n a n d has b ee n effecti v e i n treati n g ot her ca us es of diarr he a.  
It has bee n a p pr o ve d b y t he F D A, b ut has n ot bee n a p pr o v e d f or use i n 
l y m p h oc ytic c olitis. 
 
H o w m a n y pe o ple will t a ke p art i n t he st u d y ?  
 
T he pla n is t o ha ve 3 0 pe o ple ta ke part i n t his st u d y.  All will be e nr olle d at Ma y o. 
 
 
W h at will h a p p e n i n t he st u d y ?   
 
Wit hi n t w o wee ks pri or t o starti n g t he st u d y me dicati o n, y o u will u n der g o a 
p h ysical e xa mi nati o n, a re vie w of y o ur me dic al hist or y, a n d scree ni n g bl o o d a n d 
st o ol tests if necessar y as part of a r e g ular cli nical e val uati o n.  I n a d diti o n, 
c ol o n osc o p y or si g m oi d osc o p y (s c o pe i nt o t h e c ol o n) wit h bi o psies ma y be ta ke n if 
necessar y.  If t hese tests i n dicate t hat l y m p h oc ytic c olitis is t he o nl y c a use f or y o ur 
diarr hea, y o u will b e as ke d t o fill o ut a si m ple, o ne pa ge f or m descri bi n g y o ur 
diarr hea a n d ot her s y m pt o ms.  Y o u will als o b e as ke d t o st o p y o ur di arr hea 
me dicati o ns a n d f oll o w y o ur diarr h ea a n d ot her s y m pt o ms f or o n e we e k.  At t hat 
p oi nt, it will be deci de d if y o u q u alif y f or t he st u d y.  
 
If y o u q ualif y f or t h e st u d y, y o u will s u b mit a st o ol sa m ple a n d h a ve a s mall 
a m o u nt of bl o o d dra w n.  If y o u are a fe male a ble t o ha ve c hil dre n, s o me of t he 
bl o o d will be use d t o b e s ure y o u are n ot pr e g na nt.  I n a d diti o n, if y o u ha ve n ot ha d 
bi o psies fr o m y o ur c ol o n i n m ore t ha n o n e ye ar as part of y o ur re g ul ar me dical 
care, y o u will ha ve a re peat si g m oi d osc o p y a n d bi o psies as part of t h e st u d y.   
 

2 2 
T he n, if y o u are n ot pre g na nt, y o u will be p ut i n o ne of t w o gr o u ps b y c ha nce (as i n 
t he fli p of a c oi n).  O ne gr o u p will recei ve b u d es o ni de i n t he f or m of 3 milli gra m 
ta blets.  T h e ot her gr o u p will recei v e a pl ac e b o (s u g ar)  t a blet.  S u bje cts i n eac h 
gr o u p will ta ke t hre e ta blets per da y f or ei g ht wee ks. T he 9 milli gra m d ose of 
b u des o ni de will be use d i n t his st u d y as it has bee n f o u n d t o be effe cti ve i n treati n g 
ot her t y pes of diarr h ea. 
 
F or t he ei g ht wee k d ur ati o n of t he st u d y, y o u will be as ke d t o kee p a si m ple dail y 
rec or d of y o ur diarr h ea a n d ot her s y m pt o ms.  T he st u d y assista nt will call y o u o n 
t he tele p h o ne o nce p er wee k t o see h o w y o u ar e d oi n g.  At t he e n d of ei g ht wee ks, 
t he st u d y me dicati o n will be st o p pe d.  Y o u will s u b mit a sec o n d st o ol sa m ple.  A 
re peat si g m oi d osc o p y (sc o pe i nt o t he l o wer c ol o n) wit h bi o psies will be perf or me d 
at Ma y o wit hi n se ve n d a ys.  T his pr oce d ure is part of t he st u d y a n d t h eref ore will 
n ot be bille d t o y o u or y o ur i ns ura nce c o m pa n y.  If y o ur s y m pt o ms h a ve i m pr o ve d 
o n treat me nt, we will f oll o w y o u o ver t he ne xt f o ur wee ks t o see if y o ur s y m pt o ms 
ret ur n after t he me dic ati o n is st o p pe d. 
 
D uri n g t he st u d y, y o u s h o ul d n ot use a n y ot her me dicati o ns f or diarr h ea e xce pt 
t h ose y o u ha ve disc uss e d wit h y o ur d oct or, i n cl u di n g o ver-t he-c o u nt er ( n o n-
prescri pti o n) me dicati o ns.  Y o u will be a ble t o use I m o di u m (l o p era mi de) t o 
c o ntr ol y o ur diarr he a if y o u are ha vi n g m ore t ha n si x b o wel m o ve me nts per da y, 
b ut y o u s h o ul d n ot use a n y ot her di arr hea m e dicati o ns wit h o ut c o ntacti n g t he 
d oct or or st u d y assista nt. 
 
 
H o w l o n g will I be i n t he st u d y ?  
 
Y o u will b e i n t he st u d y f or ei g ht wee ks, wit h f o ur a d diti o nal wee ks of f oll o w u p if 
y o u res p o n d t o t he me dicati o n. 
 
 
Are t here re as o ns I mi g ht le a ve t his rese arc h st u d y e arl y ? 
 
Ta ki n g part i n t his rese arc h st u d y is y o ur decisi o n.  Y o u ma y deci de t o st o p at a n y 
ti me.  Y o u s h o ul d tell t he researc her if y o u d e ci de t o st o p a n d y o u will be a d vise d 
w het her a n y a d diti o nal tests ma y n ee d t o b e d o ne f or y o ur safet y.  
 
I n a d diti o n, t he rese arc hers or Ma y o ma y st o p y o u fr o m t a ki n g p art i n t his st u d y at 
a n y ti me if it is i n y o ur best i nterest, if y o u d o n ot f oll o w t he st u d y r ul es, or if t he 
st u d y is st o p pe d. 
 
 
Will a n y bi ol o gi c al s a m ple(s) be st ore d a n d use d f or rese arc h i n t he f ut ure ? 
 
N o.  Y o ur sa m ples will be use d as descri be d f or t his st u d y, t he n t he y will be 
destr o ye d.  
 
 

2 3 
W h at are t he ris ks of t he st u d y ? 
 
As wit h a n y me dic ati o n, aller gic rea cti o ns t o b u des o ni de are a p ossi bilit y.  Ot her 
a d verse e ve nts ass ociat e d wit h b u des o ni d e ma y i ncl u de he a dac he, r es pirat or y 
i nfecti o n, na usea or v o miti n g, bac k pai n, st o m ac h pai n, diz zi ness, gas, a n d fati g ue.  
W hile y o u are ta ki n g p art i n t his st u d y, y o u ar e at ris k f or t hese si de effects.  Y o u 
s h o ul d tal k t o y o ur st u d y d oct or a n d/ or y o ur m e dical d oct or a b o ut t hese si de 
effects.  T her e als o ma y be ot her si de effects t hat are n ot k n o w n.  Ot h er dr u gs ma y 
be gi ve n t o ma ke si de effects less s eri o us a n d l ess u nc o mf orta ble.  Ma n y si de 
effects g o a wa y s h ortl y after t he b u des o ni d e is st o p pe d, b ut i n s o me c ases si de 
effects ca n be seri o us or l o n g lasti n g. 
 
T he ris ks of dra wi n g bl o o d i ncl u de pai n, br uisi n g, or rarel y, i nfecti o n at t he site of 
t he bl o o d dra w. 
 
A fle xi ble si g m oi d osc o p y ma y ca use a b d o mi n al disc o mf ort a n d cr a m pi n g.   T he 
ris k of seri o us si de effe cts s uc h as hea v y bl ee di n g a n d perf orati o n ( pr o d uci n g a 
h ole i n t he c ol o n) fr o m t he pr oce d ure is rare (l ess t ha n o n e perce nt). 
 
T here is n ot e n o u g h me dical i nf or mati o n t o k n o w w hat t h e ris ks mi g ht be t o a 
breast-fe d i nfa nt or t o a n u n b or n c hil d carri e d b y a w o ma n w h o ta kes part i n t his 
st u d y.  T heref ore, pre g n a nt w o me n  a n d n ursi n g m ot hers ma y n ot partici pate i n 
t his st u d y.  F urt h er m or e all w o me n w h o ca n b ec o me pre g n a nt a n d ar e se x uall y 
acti ve, or t heir se x ual p art ners, m ust use birt h c o ntr ol meas ures w hile i n t his st u d y.  
T he f oll o wi n g birt h c o ntr ol meas ures are ac ce pta ble: birt h c o ntr ol pills, c o n d o ms, a 
dia p hra g m, or a n i ntra uteri ne de vice.  Breast-f ee di n g m ot hers m ust st o p breast-
fee di n g t o ta ke part i n t his st u d y.  W o me n w h o ca n bec o m e pre g na nt m ust ha ve a 
pre g na nc y test bef ore t a ki n g part i n t his st u d y.  F or t he pr e g na nc y test, bl o o d will 
be ta ke n fr o m a vei n i n y o ur ar m wit h a ne e dl e 1- 2 da ys bef ore t he st u d y.  Y o u will 
be t ol d t he r es ults of t h e pre g na nc y test.  If t he pre g na nc y t est is p ositi ve, y o u will 
n ot be a ble t o ta ke p art i n t he st u d y. If y o u bec o me pre g na nt d uri n g t h e st u d y, y o u 
m ust i m m e diatel y disc o nti n ue t he st u d y dr u g a n d i nf or m t he i n vesti g at ors. 
 
 
Are t here b e nefits t o t a ki n g p a rt i n t his st u d y ?  
 
T his st u d y ma y n ot ma ke y o ur healt h better.  H o we ver, i n pre vi o us st u dies of 
b u des o ni de i n c olla ge n o us c olitis, 5 0- 1 0 0 % of partici pa nts res p o n de d t o t he 
me dicati o n wit h i m pr o ve me nt i n t heir diarr he a.  T heref ore, t here is r eas o n t o 
e x pect t hat b u des o ni de ma y hel p y o ur diarr hea.  H o we ver, t here is a c ha nce t hat 
y o u c o ul d r ecei ve t h e place b o me di cati o n, a n d t heref ore n o defi nite b e nefit ca n be 
e x pecte d fr o m partici p ati o n i n t his st u d y. 
 
 
W h at ot h er c h oices d o I h a ve if I d o n’t t a k e p art i n t his st u d y ?  
 
Y o u d o n ot ha ve t o be i n t his st u d y t o recei ve treat me nt f or y o ur c o n diti o n.  If y o u 
deci de n ot t o partici pat e i n t his st u d y, a n ot her a nti- diarr hea or a nti-i nfla m mat or y 

2 4 
me dicati o n, i ncl u di n g b u des o ni de, ma y b e tri e d.  Y o u s h o ul d tal k t o t he researc her 
a n d y o ur re g ular d oct or a b o ut eac h of y o ur c h oices bef ore y o u deci d e if y o u will 
ta ke part i n t his st u d y. 
 
 
Will I nee d t o p a y f or t he tests a n d pr o ce d u res ? 
 
Y o u will n ot nee d t o pa y f or a n y tests a n d pr oc e d ures t hat are d o ne j ust f or t his 
researc h st u d y.  T hese t ests a n d pr oce d ures are t he fle xi ble si g m oi d os c o p y a n d 
c ol o n bi o psies, t he bl o o d w or k, a n d t he st o ol st u dies.  H o we ver, y o u a n d/ or y o ur 
healt h pla n will nee d t o pa y f or all ot her tests a n d pr oce d ur es t hat y o u w o ul d 
n or mall y ha ve as part of y o ur re g ul ar me dic al care.  T hese t ests a n d pr oce d ures are 
t he office visit, bl o o d a n d st o ol tests a n d t he si g m oi d osc o p y d o n e bef ore y o u are 
e nr olle d i nt o t he st u d y.  
 
T he st u d y me dicati o n will be pr o vi de d fre e of c har ge. 
 
 
W h at h a p pe ns if I a m i nj ure d bec a use I t o o k p art i n t his st u d y ?  
 
If y o u ha ve si de effects fr o m t he st u d y treat me nt, y o u nee d t o re p ort t he m t o t he 
researc her a n d y o ur re g ular d oct or, a n d y o u will be treate d as nee de d.  Ma y o will 
bill y o u or y o ur i ns urer f or t hese ser vices at t h e us ual c har ge.  Ma y o will n ot off er 
free me dical c are or pa y me nt f or a n y ba d si de effects fr o m ta ki n g part i n t his st u d y.  
Me dical ser vices nec essar y f or a res earc h relat e d ill ness or i nj ur y will be c o vere d 
b y Astra- Ze neca, t he st u d y s p o ns or, t o t h e e xt e nt t he y are n ot c o vere d b y y o ur 
healt h i ns ur a nce.  
 
 
W h at are m y ri g hts if I t a ke p a rt i n t his res e arc h st u d y ? 
 
Ta ki n g part i n t his res earc h st u d y d oes n ot t a ke a wa y a n y ot her ri g hts or be nefits 
y o u mi g ht ha v e if y o u di d n ot ta ke part i n t he st u d y.  Ta ki n g part i n t his st u d y d oes 
n ot gi ve y o u a n y s peci al pri vile ges.  Y o u will n ot be pe nalize d i n  a n y wa y  if y o u 
deci de n ot t o ta k e part or if y o u st o p after y o u start t he st u d y.  S pecificall y, y o u d o 
n ot ha ve t o be i n t his st u d y t o recei v e or c o nti n ue t o recei ve me dical care fr o m 
Ma y o Cli nic.  If y o u st o p t he st u d y y o u w o ul d still recei ve me di cal care f or y o ur 
c o n diti o n.  
 
Y o u will b e t ol d of i m p orta nt ne w fi n di n gs or a n y c ha n ges i n t he st u d y or 
pr oce d ures t hat ma y affect y o u or y o ur willi n g ness t o c o nti n ue i n t he st u d y. 
 
 
W h o c a n a ns wer m y q uesti o ns ? 
 
Y o u ma y tal k t o Dr. Par di at a n y ti me a b o ut a n y q uesti o n y o u h a ve o n t his st u d y.  
Y o u ma y c o ntact Dr. P ar di ( or a n ass ociate) b y calli n g t h e Ma y o o perat or at 
 
.  
 

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Y o u ca n get f urt her i nf or mati o n a b o ut Ma y o p olicies, t he c o n d uct of t his st u d y, or 
t he ri g hts of researc h s u bjects fr o m 
, A d mi nistrat or of t he Ma y o 
F o u n dati o n Office f or H u ma n Researc h Pr ote cti o n, tele p h o ne 
 
. 
 
 
 
A ut h oriz ati o n T o Use A n d Discl ose Pr otecte d He alt h I nf or m ati o n  
 
B y si g ni n g t his f or m, y o u a ut h orize Ma y o Cli nic R oc hes ter a n d t he i n vesti gat ors t o 
use  a n d  discl ose  a n y  i nf or mati o n  cre ate d  or  c ollecte d  i n  t he  c o urse  of  y o ur  
partici pati o n i n t his res earc h pr ot oc ol. 
 
T his i nf or m ati o n ma y be gi ve n t o ot her researc hers i n t his st u d y, re prese ntati ves of 
t he c o m pa n y s p o ns ori n g t he st u d y, or pri vat e, state or fe deral g o v er n me nt parti es 
res p o nsi ble f or o verse ei n g t his res earc h.  T h ese ma y i ncl u de t he F o o d a n d Dr u g 
A d mi nistrati o n, t he Office f or H u ma n Resear c h Pr otecti o ns or ot her offices wit hi n 
t he De part me nt of He alt h a n d H u ma n Ser vi ces, a n d t he Ma y o F o u n dati o n Offic e 
f or  H u ma n  Resear c h  Pr otecti o ns  or  ot her  Ma y o  gr o u ps  i n v ol ve d  i n  pr otecti n g  
researc h s u bjects. 
 
T his i nf or mati o n will b e gi ve n o ut f or t he pr o per m o nit ori n g of t he st u d y, c hec ki n g 
t he acc urac y of st u d y data, a nal y zi n g t he st u d y data, a n d ot her p ur p oses necessar y 
f or t he pr o p er c o n d u ct a n d re p orti n g of t his st u d y. 
 
T his a ut h orizati o n l asts u ntil t he e n d of t he st u d y. 
 
Y o u ma y st o p t his a ut h orizati o n at a n y ti me e xce pt if Ma y o Cli nic R oc hester  nee ds 
i nf or mati o n alrea d y c ollecte d t o e ns ure c o m plete a n d acc urat e st u d y res ults.  T his 
mi g ht mea n t hat Ma y o ma y c o nti n ue t o use y o ur i nf or mati o n c olle cte d as part of 
t his st u d y e ve n after y o u ha ve t ol d us t o st o p.  If t his is a researc h st u d y t hat als o 
i n v ol ves treat me nt, y o u ma y n o l o n ger be eli gi ble t o recei v e st u d y treat me nt if y o u 
tell Ma y o t o st o p usi n g t his i nf or mati o n.  T h e o nl y wa y y o u ca n tell Ma y o t o st o p 
usi n g t he i nf or mati o n is i n writi n g a d dresse d as f oll o ws: 
 
Ma y o F o u n dati o n 
Office f or H u ma n R ese arc h Pr otecti o ns 
A T T N:  N otice of Re v ocati o n of A ut h oriz ati o n 
2 0 0 First St. S W 
R oc hester, M N 5 5 9 0 5 
 
If t his i nf or mati o n is gi ve n o ut t o s o me o n e els e, t he i nf or mati o n ma y n o l o n ger b e 
pr otecte d b y fe deral pri vac y re g ulati o ns a n d m a y be gi ve n o ut b y t he pers o n or 
e ntit y t hat r ecei ves t he i nf or mati o n. 
 
A c o p y of t his f or m will be place d i n y o ur me dical rec or d. 
 
 
 

2 6 
I h a ve h a d a n o p p ort u nit y t o h a ve m y q uesti o ns a ns were d.  I h a ve bee n 
gi ve n a c o p y of t his f or m.  I a gree t o t a ke p art i n t his rese arc h st u d y.   
  
 
 
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( Date) 
( Pri nte d Na me of Partici pa nt) 
( Cli nic N u m ber) 
 
 
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( Si g nat ure of Partici pa nt)                        
 
 
 
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( Date) 
( Pri nte d Na me of I n di vi d ual O btai ni n g C o nse nt) 
 
 
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( Si g nat ure of I n di vi d ual O btai ni n g C o nse nt)