Clinical trial NCT00217022
Conditions: Lymphocytic Colitis Diarrhea
Keywords: Lymphocytic Colitis diarrhea budesonide
Sponsor: Mayo Clinic
Start date: 2003-06-01; Completion date: 2008-02-01
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Patients will receive budesonide or placebo for the treatment of active lymphocytic colitis. This study includes stool collections, blood draws, weekly questionnaires and a sigmoidoscopy. The study hypothesis is that budesonide will be safe and effective compared with placebo for the treatment of diarrhea in lymphocytic colitis.

Detailed description:
Microscopic colitis is an increasingly diagnosed cause of chronic diarrhea, with two main subtypes: collagenous and lymphocytic colitis. Uncontrolled reports have suggested that various drugs can be beneficial in treating microscopic colitis, but few treatments have been evaluated in randomized controlled trials. Thus, treatment is guided mostly by anecdotal reports, case series, and physicians' experience. In our uncontrolled experience, corticosteroids are one of the most effective therapies for microscopic colitis, but are not typically used as a first line therapy because of toxicity. Budesonide has been reported to be of clinical benefit in small, uncontrolled series of patients with microscopic colitis, and recent controlled trials showed that it is superior to placebo in collagenous colitis. We propose a study of budesonide in patients with the lymphocytic type of microscopic colitis.

Patients will have stool specimen and blood drawn at the start of the study. Patient will take either Budesonide or placebo for 8 weeks. At the end of treatment, patient will have stool collection and sigmoidoscopy.

Arms: arm 1: 9 mg daily arm 2: three tablets daily
Interventions: intervention 1: Placebo intervention 2: Budesonide
Intervention descriptions: intervention 1: Placebo, 3 tablets daily intervention 2: 9 mg daily (three tablets)

Protocol documents:
Prot_SAP_ICF_000.pdf: 
 
 
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 
 
.  
 


2 5 
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)