Clinical trial NCT02160288
Conditions: Obstructed Defecation Syndrome (ODS)
Keywords: Botox Obstructed Defecation Syndrome ODS Outlet-Type Constipation injection
Sponsor: Massachusetts General Hospital
Start date: 2016-02-01; Completion date: 2019-06-11
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if Botulinum Toxin-A (Botox) injection will improve symptoms of constipation in obstructed defecation syndrome (ODS).

Detailed description:
Constipation represents one of the five most common physician diagnoses for gut disorders. Obstructed defecation syndrome (ODS) is an under-treated condition which accounts for 30%- 50% of all patients with constipation and it is more common as people age. ODS is due to the abnormal contraction of the puborectalis muscle (a muscle around the anus that should relax during defecation).

Biofeedback therapy and medical management are the standards of care for ODS. Typically patients are first managed with dietary modifications (fiber supplementation, increased fluids) and medication (laxatives, enemas). If constipation is not improved, they will undergo biofeedback, which lasts from 3-8 sessions on average. Biofeedback acts on the cause of ODS and it has good short-term success, but around 50%-70% of treated patients re-experience constipation after one year. The main drawbacks of biofeedback for ODS are the facts that it is expensive, time-consuming, available in few select-centers and its success depends very much on the provider. Biofeedback is delivered in multiple 1-hour clinic sessions, so many patients don't finish all recommended sessions and their constipation may recur faster.

Botox also acts on the cause of ODS and was shown to improve constipation within 1-3 weeks after the injection. Botox is delivered as a one-time injection in the puborectalis muscle and external anal sphincter (the muscle right around the anus). The injection can be performed in the clinic under local anesthesia, and the patient goes home afterwards. Currently, Botox is used for treatment of patients who fail biofeedback and medical management, to avoid the options of last resort (resection of the colon with stoma). To this day, no adequately designed study has confirmed that Botox is indeed superior to placebo (normal saline) for the treatment of ODS. The results from this study will provide valuable data on the ability of Botox to improve symptoms of constipation and the duration of its effect. This project has the potential to increase the availability of effective treatments for ODS.

Arms: arm 1: Patients will receive Botulinum Toxin-A (Botox) injected in the puborectalis muscle and external anal sphincter. We will use 100 units of Botox, a dose with a good safety profile that has been proven to work in previous studies performed in adults. arm 2: Patients will receive normal saline (placebo) injected in the puborectalis muscle and external anal sphincter.
Interventions: intervention 1: Botulinum Toxin-A intervention 2: Normal Saline
Intervention descriptions: intervention 1: 100 Units diluted in a 5 cc syringe at a concentration of 20U/mL intervention 2: Dispensed in a 5 cc syringe

Protocol documents:
Prot_SAP_000.pdf: 
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Effects of Botox in Obstructed Defecation Syndrome 
 
NCT02160288 
 
 


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Effects of Type A botulinum toxin in obstructed defecation syndrome: a Phase II randomized, 
parallel group, triple-blind, placebo- controlled trial 
 
 
 
I. 
BACKGROUND AND SIGNIFICANCE 
 
a. Historical background 
 
Constipation represents one of the five most common physician diagnoses for gastrointestinal 
disorders1. Obstructed defecation syndrome (ODS) accounts for 30%-50% of all patients with 
constipation and its prevalence, health care costs and impact on the quality of life can be assessed 
indirectly from data available on constipation2. 
 
A 2011 review and meta-analysis of chronic idiopathic constipation worldwide identified a pooled 
global prevalence of 14%2. Another recent review on the epidemiology of chronic constipation 
identified a median prevalence of 16% (ranging from 0.7%-79%) in adults overall and 33.5% in 
adults aged 60 to 101 years3. In North America, over 63 million people met the Rome II criteria for 
constipation8 .  
 
Although only a minority of patients suffering from constipation seeks medical advice4, constipation 
consumes significant health care resources because its prevalence is high10. The most recent data 
from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical 
Care Survey show that the number of ambulatory visits for constipation has doubled over a ten-year 
period5. From 1997 to 2006, a total of 52.7 million patient visits in the U.S. were related to 
constipation. The annual direct medical costs for constipation were estimated to exceed $230 
million6-7. Recent studies suggest that among patients with constipation in the community, quality of 
life scores were comparable to those suffering from depression, hypertension and diabetes9 . 
 
Symptoms of constipation can be secondary to mechanical obstructions of the colon, drug side 
effects, and neurologic or metabolic disturbances16. Most frequently, however, constipation is 
caused by disordered function of the colon, pelvic floor or anorectal apparatus. Based on assessment 
of colonic transit and anorectal function, patients can be categorized in three groups: normal transit 
constipation, slow transit constipation and defecatory disorders. Defecatory disorders (DD), also 
known as obstructed defecation, may coexist with slow transit constipation. The American 
Gastroenterological Association (AGA) and Rome III criteria both emphasize the need to diagnose 
DD, because when evacuatory defects are pronounced, soft stools and even enema fluid may be 
difficult to pass16. 
 
Obstructed defecation syndrome (ODS) is defined as the inability to defecate properly, despite a 
normal sensation of the need to do so13. This leads to the feeling of incomplete evacuation with long, 
frequent toilet visits, straining, digitation, and laxative abuse. In most cases of ODS, abnormal 
morphology of the pelvis, the pelvic floor and the colon and rectum may be present14. Although 
structural abnormalities coexist, the etiology of ODS is incompletely understood and may be 
conceptualized as maladaptive learning of sphincter contraction16. Even the findings of different 
tests (eg, anal manometry, defecography) may not concur. There is no gold standard for the 


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diagnosis and traditional treatment approaches (fiber, osmotic or stimulant laxatives and enemas) do 
not improve the anorectal muscular coordination and may exacerbate the problem. 
Biofeedback therapy improves corticoanal function26 and it alongside of medical management, is the 
mainstay of treatment of DD. Its main advantages are that it is noninvasive, free of morbidity and 
with a documented success rate of over 70%16. The short-term success rate for biofeedback therapy 
depends on the patient’s motivation, the operator’s expertise and skills, and the quality of their 
interaction with the patient. Successful protocols from tertiary centers have used 5-6 treatment 
sessions, lasting 30-60 minutes each at two weekly intervals17. While the short-term success rates 
support the use of biofeedback, there is a high failure rate of about 50%-70% at one year. The main 
drawbacks of biofeedback for ODS are the facts that it is expensive, time-consuming, and it has 
decreased availability and inconsistent outcomes which are very provider dependent. Because it is 
delivered in multiple clinic sessions, it is associated with a poorer patient compliance. 
There is no current standard of care for patients with refractory defecatory disorders who fail a trial 
of medication and biofeedback therapy. Options are limited to sacral nerve stimulation, botulinum 
toxin injection or surgical interventions. Patients who fail, refuse or do not finish biofeedback 
therapy may be offered botulinum toxin injections into the puborectalis muscle36. Sacral nerve 
stimulation has recently been proven to work for patients with defecatory disorders accompanied by 
rectal hyposensitivity, but studies are very small, uncontrolled and the response to treatment is 
inconsistent27. Studies assessing the value of partial division of the puborectalis muscle reported 
mixed results and permanent complications, including incontinence for gas, mucus or feces29,37. 
Total abdominal colectomy with ileorectal anastomosis is the surgical option reserved for patients 
with chronic constipation who have failed medical therapy. Preliminary studies have shown that it 
offers significant symptomatic improvement35, however, like any major surgical procedure, there is 
a higher risk for complications. An end ileostomy or, if colonic transit is normal, a colostomy are the 
options of last resort for most patients.  
 
b. Previous clinical studies 
 
Botulinum neurotoxin A is one of the seven neurotoxins produced by Clostridium botulinum.19-
20 When injected into the muscle, it binds very specifically to the presynaptic membrane of 
motoneuron nerve endings and produces chemodenervation that can last for 14 to 16 weeks21-
22. This long-lasting neuromuscular blockade is achieved through the cleavage of nine amino-
acid residues from the carboxyl terminus of synaptosome-associated protein with relative 
molecular mass 25K (SNAP-25)24-25. As a consequence, acetylcholine-containing synaptic 
vesicles can no longer fuse with the plasma membrane, resulting in the blockade of 
neurotransmission. The injected muscles become weak over 2-20 days and may recover over 
2-4 months as new terminal axons sprout and restore neurotransmission.23  
 
Botox was first documented for use in the treatment of anismus in 1988, with a symptomatic 
improvement in 4 of 7 patients (57%) at 4 weeks after the injection28. This was a pilot study 
and different doses of Botox were used. Two patients developed fecal incontinence that 
disappeared once the effect of Botox started to fade. 
 


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Several phase I and II trials since then demonstrated that Botox is a safe and effective 
therapeutic approach for ODS28-35. There were no severe adverse effects and the overall 
mortality rate was 0% in all of these studies.  Subject to the caveats that the majority of these 
studies were uncontrolled, with small sample sizes, variable doses, primary outcomes and 
administration modalities of Botox, their encouraging results led to Botox being increasingly 
used off-label for patients with pelvic floor disorders who failed medical management and 
biofeedback therapy.  It offers significant advantage in the fact that it can be administered in 
one session in the office. 
 
Joo et al. 31 injected a dose of Botox contingent with body mass (a total of 12-30 units) in 4 
patients with anismus who had failed biofeedback therapy. Symptomatic improvement was 
noted in all subjects (100%) at 1 and 3 months after the injection. The effect was maintained at 
one year in 50% of their patients. Shafik and El-Sibai35 injected 25 IU of Botox in the external 
anal sphincter of 15 patients with nonrelaxing puborectalis muscle syndrome. Straining at 
defecation disappeared and stool frequency normalized in 13 of 15 patients (87%) with a 
mean duration of effect of 4.8 +/- 1.4 SD months. None of the patients treated with Botox 
reported any adverse effects after the injection. 
 
In 2006, Maria et al. 30 injected 60 IU of Botox in the nonrelaxing puborectalis muscle of 24 
patients with chronic outlet obstruction constipation.  At 2 months, 19 of 24 patients (79%) 
had symptomatic improvement. The other five patients who did not respond to the first dose 
were offered a rescue treatment with 100 IU of Botox. All of them had symptomatic 
improvement after two months and this improvement persisted to the end of follow-up. At 4 
months, 4 of the 19 patients (21%) who initially improved suffered symptomatic recurrence 
and were successfully retreated with 100 IU of Botox. At an average follow-up of 39+/-17 
months, there was no symptomatic recurrence in any of the 24 patients. Two patients (8%) 
had mild flatus incontinence after the first injection, but there were no other short- or long-
term complications or side effects. 
 
Ron et al32 randomized 25 patients with anismus to receive 20 IU of Botox with two different 
methods of administration (local injection of Botox-10 units to each side of the puborectalis or 
20 units to the posterior aspect of this muscle). Only 29% had a symptomatic improvement in 
straining index after this dose and the overall satisfaction rate with the treatment was 58%. 
The reported adverse effects were: 0% incontinence, local infection or bleeding (these remained 
the same during follow-up after the 1st and 2nd injection). 12.5% of all patients developed mild pain 
after injection that increased at follow-up. 
 
Faried et al. 29 randomized sixty patients with anismus to receive biofeedback therapy, 100 IU 
of Botox or posterior division of the puborectalis muscle in. The groups differed significantly in 
terms of clinical improvement at 1 month (50% for biofeedback, 75% Botox injection, 95% 
posterior division of the puborectalis muscle, p=0.006). The symptomatic improvement 
persisted at 1 year in 30% of patients in the biofeedback group, 35% in the Botox group and 
70% in the surgery group (p=0.02). No adverse effects were reported for the Botox arm. Two 
patients in the surgery arm developed incontinence, compared to 0 patients in the Botox and 
biofeedback arms.  


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Hompes et al. 36 reported an excellent response of patients with anismus to 100 IU of Botox. 
Twenty-two (39%) of 56 patients responded initially and 21 ⁄ 22 (95%) underwent repeat injection. 
At a median follow-up of 19.2 (range, 7.0–30.4) months, 20 ⁄ 21 (95%) had a sustained response and 
required no further treatment. In 33 (97%) of 34 nonresponders, significant abnormalities were 
demonstrated at EUA: 31 (94%) had a grade 3–5 rectal prolapse, one had internal anal sphincter 
myopathy and one had a fissure. Exclusion of these alternative diagnoses revised the initial response 
rate to 96%. Of 56 patients who received the injection, 4 (7.1%) developed transient minor fecal 
incontinence (for gas rather than minor soiling). These adverse effects occurred in 4/16 patients who 
ultimately proved to have rectal prolapse. No Patient with ODS alone had any continence 
disturbance. 
 
In summary, doses between 50-100 IU of Botox are safe, well tolerated and have been shown 
in small studies without blinding to provide immediate symptomatic relief in the majority of 
patients with ODS constipation. For those who did not respond to low doses, higher doses of 
100 IU have been used successfully, with improvement in 90-100% of the cases. Based on the 
available evidence, Botox is a reasonable therapeutic option after failure of conservative 
management and before more invasive surgery is attempted 34. 
 
c. Rationale behind the proposed research and potential benefits to patients and society 
 
ODS is an undertreated condition, whose prevalence increases with age and is predicted to increase 
dramatically with the aging population. Botox has been proposed as an effective treatment and it has 
long been used off-label in ODS patients who refused or failed medical management and 
biofeedback therapy.  However, to this day, no randomized controlled trial has confirmed that Botox 
is superior to placebo for the treatment of ODS. 
 
We will use 100 IU of Botox, a dose with a good safety profile that has been proven to work in 
previous studies. We want to evaluate the efficacy of Botox 100 IU compared to placebo in addition 
to the standard of care (biofeedback therapy) in the treatment of patients diagnosed with ODS. We 
also plan to document patient compliance with biofeedback therapy. 
 
 
II. SPECIFIC AIMS 
 
Objective: 
To evaluate the efficacy and safety of Botox for the treatment of ODS. 
 
Hypotheses: 
Patients treated with Botox will have an improvement in the Altomare Obstructed Defecation 
Syndrome score (ODS-S) and Patient Assessment of Constipation- Quality of Life Score (PAC-
QoL) compared to the placebo group. 
 
 
 
 


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III.SUBJECT SELECTION 
 
a. Inclusion/exclusion criteria 
 
Inclusion criteria  
- 
Males and females older than 18 years of all races and backgrounds 
- 
Competent to give informed consent 
- 
Meet the Rome III diagnostic criteria for functional constipation 
- 
Inability to relax the puborectalis muscle at electromyography  
- 
Altomare Obstructed Defecation Syndrome score of 15 points or above  
- 
Failure of treatment with 2 conservative measures which may be as follows: 
o 1 laxative (osmotic or stimulant) for 2 weeks 
o 1 fiber supplement for one month 
o And/or trial of biofeedback for at least 4 sessions 
 
 
Exclusion criteria 
- 
Previous treatment with botulinum toxin (possible antibodies) 
- 
Known hypersensitivity to any of the components of the toxin 
- 
Presence of allergy or allergic reaction to bupivacaine 
- 
Medication regimen includes narcotics 
- 
Previous radiation therapy to the anal canal and rectum 
- 
Prior proctectomy 
- 
Presence of unhealed and symptomatic anal fissure 
- 
Presence of anal pain  
- 
Presence of fecal incontinence 
- 
Presence of full thickness rectal prolapse 
- 
Presence of internal sphincter myopathy 
- 
Inflammatory bowel disease or proctitis 
- 
Pregnancy or breast-feeding 
- 
Subject is currently enrolled/ just finished participating in a clinical trial in which the 
intervention/ its carry-over effect may interact with the intervention in this trial 
 
b. Source of subjects and recruitment methods 
 
All patients seen through the Pelvic Floor Disorder Service in colorectal surgery and 
gastroenterology at MGH who are diagnosed with outlet obstruction will be told about the option to 
participate in the study by their treating physician/ nurse practitioner. 
 
 
IV. SUBJECT ENROLLMENT 
 
a. Methods of enrollment 
 


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We will enroll 23 patients into the control and 23 patients into the placebo arm of the study. All 
patients with ODS who are evaluated in the Pelvic Floor Disorders Service at MGH through 
colorectal surgery and gastroenterology will be informed of the study.  
b. Lieba Savitt, N.P. and Holly Milch, NP, initially treats most patients presenting with ODS in our 
department. Patients with ODS who fail dietary modifications and medical therapy (laxatives 
and/or biofeedback) are then referred to Liliana Bordeianou, M.D., for discussion of surgical 
options. In order to avoid the possibility of patients feeling obligated to participate, patients who 
failed medical management and are interested in participating will initially discuss the study with 
one of the NPs and have all of their questions answered. Each patient will also receive 
individualized information about the available treatment options for his/her disease. If still 
interested, they will be screened based on inclusion and exclusion criteria, and those who qualify 
will be given the informed consent to take home, read carefully and call back if they wish to 
participate. Patients who call back will be seen again and allowed to discuss the study in detail 
with the PI. All further questions will be answered prior to signing consent. If still interested in 
participation, patients will sign the informed consent with their physician and then schedule their 
intervention following consent signing.  
 
c. Treatment assignment and randomization 
 
This will be a randomized controlled trial to determine the efficacy of Botox 100 IU compared to 
placebo for symptom control in adults diagnosed with ODS. Eligible patients who consented to 
participate are randomized in two groups in a 1:1 ratio to receive either 100 units of Botox or 
placebo (normal saline) administered under local anesthesia in one office session.  
 
A triple-blinded approach will be used in this study. Subjects, investigators and outcome assessors 
will be blinded to the group allocation. 
Patient treatment group allocation will be done using the method of randomly permuted blocks with 
random block sizes. This selected type of restricted randomization allows balancing group sizes 
especially in smaller randomized controlled trials. Subject randomization will be computer generated 
through the research pharmacy.  These results are subsequently kept in the research pharmacy and 
with the unblinded research nurse who will not interact with the patients 
 
On the day of the procedure, the research nurse will obtain the saline or Botox from the research 
pharmacy in a brown paper bag. She will then prepare the Botox or draw the normal saline and give 
it to the investigator for administration. In order to protect blinding, placebo and Botox will have the 
same characteristics, except for the active drug. The nurse who prepares the drug will also record the 
study arm in a file kept separate from patient information. Once this is recorded, information will be 
resealed and kept with patient information until the completion of the study. The nurse who prepared 
the composition will be the only unblinded member of the healthcare team and will not assist in the 
procedure.  
 
The adverse effects will be assessed by one standard questionnaire, which allows the description of 
idiosyncratic reactions and 2 validated questionnaires, which assess the Botox specific adverse 
effects of fecal incontinence. Outcome measurements and assessment of adverse effects in the office 
will be made by a research nurse blinded to treatment group allocation. 


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The PI who delivers the intervention will not take outcome measurements and will have no 
interaction with the data collectors. The data collectors will be blinded throughout the data entry and 
data cleaning processes. The statistical analysis will be made after the end of the data collection 
period. The statistician will only be unblinded once the database is locked. At the end of the study, 
blinding integrity will be evaluated in a sample of participants and data collectors. 
 
In case of medical emergency, if a study participant has encountered an urgent medical problem and 
the clinician needs to know his/her intervention group, the allocation code can be broken. 
Unblinding envelopes (labeled with the randomization number that contains allocation) are sealed by 
the study center and are only opened if emergency unblinding is necessary.  
 
 
 
V. STUDY PROCEDURES 
 
a. Study visits and parameters to be measured 
 
As part of this research study, patients will be asked to come for three visits (Visit 1= return of 
informed consent and schedule of intervention; Visit 2= intervention; Visit 3=one month after the 
intervention). They will afterwards be contacted by mail with questionnaires and then with follow-up 
phone calls (for those who did not return questionnaires) to increase response rate at 3, 6 and 12 
months after the intervention.  
 
All patients considered for the study will undergo pretreatment evaluation as per standard of care. 
This includes a history, clinical examination, and anorectal manometry. Once the patient is deemed 
eligible to participate, s/he will be offered the opportunity to participate in this trial. 
 
If interested, s/he will meet with the Principal Investigator and/or research nurse practitioner to find 
out more about this trial. At this time all questions will be answered. Afterwards, s/he will be offered 
an informed consent form, for review at home.  Patients will then be scheduled for a follow-up visit 
to review and sign consent with PI or study nurse practitioner.   
 
Once all questions are answered and consent is signed, patients will be asked to fill out baseline 
questionnaires at the visit when consent is signed.  
 
All questionnaires used in this study include validated scores. They will be used to assess the 
efficacy of the intervention in providing symptomatic improvement and improved quality of life 
(Altomare ODS score, generic SF-36 version 1, Patient Assessment of Constipation- Quality of Life 
questionnaire). We will also use 2 standard questionnaires to assess for Botox-specific adverse 
effects (Cleveland Clinic Fecal Incontinence Score and Fecal Incontinence Quality of Life Scale).  
 
Patients will receive the questionnaires at baseline and then be asked to complete them at their one 
month follow-up visit.   
 
At one month follow-up visit, patients will meet with their surgeon and the study nurse practitioner.  
They will first review any adverse reactions which they may have had. Patient will also be asked 


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about any adverse reactions which will be documented at that visit.  They will then undergo 
anorectal manometry and fill out the questionnaires.   
 
At 3, 6, and 12 months after the injection, patients will be mailed questionnaires.  Those participants 
who do not respond within a month will be contacted by phone to increase response rate.    
 
b. Drugs, devices and surgical procedures to be used 
 
Patients are divided in 2 groups: 
Group #1: Placebo 
 
Placebo consists of normal saline and has the same method and route of administration as the active 
treatment. 
 
Group #2: Botox 100 IU 
 
Each patient in Group #2 will receive a total of 100 units of botulinum toxin, stored in the research 
phramacy and dispensed to the clinic on the day of the procedure.  Botox will be resuspended in 5 ml 
of sterile saline to a ﬁnal concentration of 20 U/ml. 
 
For both groups, the interventions will be administered in the office under local anesthesia with 
0.25% Marcaine stored in the clinic at 20° to 25°C. We plan to use a 10 mL single dose vial of 
Marcaine (Bupivacaine Hydrochloride Injection, USP 0.25% (2.5 mg/mL)) administered as local 
infiltration. More or less drug may be used depending on each individual case. The MGH Research 
Pharmacy will perform the computerized randomization and send up medication or saline in paper 
bag based on randomization of the subject. Both saline and Botox will be brought from research 
pharmacy on the day of the procedure in a brown paper bag.   
 
The PI will use transanal ultrasound to clearly identify the puborectalis muscle. Once the muscle is 
identified, a 23-G needle will be used to inject the agent transanally into the puborectalis and 
external anal sphincter in three separate locations.  
 
c. Data to be collected  
 
All data are collected prospectively, at the pre-specified time points according to the protocol. All 
data will be collected in questionnaires attached (see above for specific description).  Data from 
baseline manometry will be taken from patient chart and recorded into REDCap database where data 
will be stored. Anorectal manometry from 1-month follow-up will also be stored in REDCap 
database. 
 
 
VI. BIOSTATISTICAL ANALYSIS 
 
a. Specific data variables being collected for the study 
 


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Data collection sheets are attached to this submission. They include the MRN to facilitate data 
extraction, demographic information (age, sex, race), diagnostic tests at baseline and the study 
endpoints collected at pre-specified times. 
b. Study Endpoints 
 
a) Primary endpoint: 
Baseline to 1 month after treatment changes in the sum of Altomare ODS score (ODS-S) and 
Patient Assessment of Constipation- Quality of Life score (PAC-QoL) 
 
b) Secondary endpoints: 
• Baseline to 1, 3, 6 and 12 months after treatment changes in Altomare ODS score (ODS-
S) and Patient Assessment of Constipation- Quality of Life score (PAC-QoL) 
• Changes in the generic SF-36 version 1, Cleveland Clinic Fecal Incontinence Score 
(CCFI) and Fecal Incontinence Quality of Life Scale (FIQoL) at 1, 3, 6 and 12 months 
from baseline 
• Relaxation of puborectalis with push measured by EMG at 1 month 
• Balloon expulsion test at 1 month 
• Manometric changes at 1 month- changes in anal sphincter function (resting sphincter 
pressure, maximal resting anal pressure, maximum squeeze pressure).  
• Change in defecation index [ Time Frame: Baseline, 1 month follow-up visit ]. The 
defecation index=maximum rectal pressure during attempted defecation/minimum 
anal residual pressure during attempted defecation. This is calculated based on 
measurements obtained from anorectal manometry and is a measure of treatment 
efficacy. 
 
c. Statistical methods 
 
All analysis will be based on intention-to-treat population in that all randomized subjects will be 
included in the analysis. 
 
Data will be expressed as mean+/- standard deviation (SD) for all continuous outcomes, and as 
counts and proportions for all categorical outcomes. The primary analysis (i.e., the comparison of 1-
month change in mean ODS-S and PAC-QoL between the 2 treatment arms) will be made by 
independent samples t-test. Comparison of treatment effect over time (i.e., 1- and 3-, 6- and 12 
months) on all scale scores will be performed by using longitudinal linear mixed effects model, 
which allows to specify the subject specific baseline levels and the time dependent response 
trajectories (i.e., slopes) random (SAS proc mixed). All p-values are two-tailed and considered 
significant if p<0.05.  
 
 
 
d. Power analysis 
 
The proposed sample size is 46 (i.e., 23 in each treatment arm). With an assumption of an attrition 
rate of up to 15%, we anticipate to attain 40 study completers.  The study is designed to detect at 


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least 25% decrease in mean ODS-S and PAC-QoL at 1 month after treatment with Botox with 80% 
power at a 5% significance level.  This effect size of ≥25% is equivalent to a decrease in mean ODS-
S decrease from 15 points at baseline to ≤ 11.4 points at 1 month37-38. 
VII. RISKS AND DISCOMFORTS 
 
a. Complications of surgical and non-surgical procedures 
 
We do not expect any unusual safety concerns in this study. The small foreseeable discomforts and 
complications will be treated as per standard of care.  
 
b. Drug side effects and toxicities 
 
Botulinum toxin (Botox) has been shown to be very safe and well-tolerated in prior studies, however 
variable doses of Botox were previously shown to have efficacy. Concerns may arise for potential 
issues with incontinence for gas, liquid or solid stool if higher doses of Botox are studied. The 
reported incidence of incontinence has been low in previous studies and it was mostly mild 
(gas>soiling>solid stool). If incontinence occurs, it may cause significant discomfort to patients who 
work in a public place and could account for a low recruitment rate and unblinding of patients who 
experience these adverse effects. Both the active treatment and placebo groups receive transanal 
injections into three sites. This can cause local discomfort/pain so we will co-administer a long-
acting local anesthetic. Patients will also be given instructions to take ibuprofen or acetaminophen as 
needed for pain relief after procedure. There is the additional risk of infection at the site of injection.  
The risk of this is low, but all patients will be instructed to call with any symptoms of infection, and 
will be seen by PI or research nurse practitioner and treated as necessary. 
 
c. Device complications/malfunctions 
 
Not applicable 
 
d. Psychosocial (non-medical) risks 
 
Psychosocial risks may include loss of productivity from appointments. We tried to limit this by 
administering our surveys via mail and phone and by asking the patients to come in only for the 
consent, intervention and one visit at 1 month afterwards.  
 
Patients who are in the control group may experience frustration with lack of improvement of their 
symptoms and frustration from the need to undergo further treatments and investigations at the end 
of the study. We tried to address this issue by encouraging all patients to receive the standard of care 
(biofeedback) prior to treatment. Also, at the end of the study, if the medication demonstrates 
efficacy for ODS, patients in the control group will be offered the option to receive Botox. These 
patients will be monitored per described plan for this study, but the subjects and investigator will no 
longer be blinded. 
 
It has been reported that patients enrolled in clinical trials are often frustrated by not knowing the 
results of their tests and the outcome of the study. To address this, patients will receive a written 
report of their objective measures (EMG, anorectal manometry, balloon expulsion test) at the one 


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month visit after the intervention. Also, we will send a letter to each patient when we receive the 
results, informing him/her of the overall outcome of this study.  
 
e. Radiation Risks 
 
Not applicable 
 
 
VIII. POTENTIAL BENEFITS  
 
a. Potential benefits to participating individuals 
 
For patients specifically, the potential benefits include an improvement of chronic constipation 
symptoms and quality of life with a minimally invasive treatment.  
 
b. Potential benefits to society 
 
For society, the potential benefits are great. At this time, few minimally invasive, easily to administer 
outpatient options for the treatment of ODS are available. The standard of care (biofeedback) is only 
available in a few select centers across the country and is not a “quick fix” taking multiple sessions 
to make progress. These may or may not accept the patients’ current insurance. On the other hand, 
the incidence of chronic constipation in the US population is clearly on the rise, as the baby boomers 
are reaching their 60s. Botox, should it be effective, could alleviate the profound suffering and 
discomfort associated with this condition. It could also provide an accessible and fast-acting option 
for the treatment of ODS. 
 
 
IX. MONITORING AND QUALITY ASSURANCE 
 
a. Independent monitoring of source data 
 
Monthly meetings will be organized to allow monitoring of recruitment of patients, and to assure 
that the IRB protocols are adhered to. The results of the study will be reviewed at 1/2 of recruitment 
goals. The study will be halted if a particular study arm appears to be more efficacious or if any 
unanticipated adverse events occur resulting in serious morbidity or mortality.  
 
 
b. Safety monitoring 
 
We do not expect any unusual safety concerns in this study as all of the treatments and procedures 
planned are FDA-approved for a different indication and are thought to be extremely safe. 
 
c. Outcomes monitoring 
 
The principal investigator will monitor completeness of data and assure the validity and integrity of 
data and adherence to the IRB-approved protocol. She will also review the accuracy and 


13 
 
Version date: 08.18.15 
 
 
completeness of case report form entries, source documents and informed consent. IRB will be 
notified of any major unforeseen complications associated with the study. 
 
d. Adverse event reporting guidelines 
 
Adverse events or other unanticipated problems will be reported to the PHRC as described in the 
PHRC policy on Adverse Event Reporting and Unanticipated Problems Involving Risks to Subjects 
or Others, which can be found on the PHRC website:  
http://healthcare.partners.org/phsirb/adverse_events.htm  
and  
http://healthcare.partners.org/phsirb/unantic.htm 
 
 
 
X. REFERENCES 
 
1. Shaheen NJ, Hansen RA, Morgan DR, et al. The burden of gastrointestinal and liver 
diseases, 2006. Am J Gastroenterol 2006;101:2128 –2138.  
2. Suares NC, Ford AC. Prevalence of, and Risk Factors for, Chronic Idiopathic 
Constipation in the Community: Systematic Review and Meta-analysiS.2Am J 
Gastroenterol 2011; 106:1582–1591; doi:10.1038/ajg.2011.164; published online 24 May 
2011 
3. Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and 
adults: a systematic review. Best Pract Res ClinGastroenterol 2011;25:3–18. 
4. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional 
gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 
1993;38:1569–1580.  
5. Shah ND, Chitkara DK, Locke GR, et al. Ambulatory care for constipation in the United 
States, 1993-2004. Am J Gastroen- terol 2008;103:1746–1753. 
6. Trinkley KE, Porter K, Nahata MC.  Prescribing Patterns for the Outpatient Treatment 
of Constipation in the United States. Dig Dis Sci (2010) 55:3514–3520 
7. Martin BC, Barghout V, Cerulli A. Direct medical costs of constipation in the United 
States. Manag Care Interface. 2006;19:43–49. 
8. Higgins PD, Johanson JF. Epidemiology of Constipation in North America: A Systematic 
Review. The American Journal of Gastroenterology (2004) 99, 750–759. 
9. Yost KJ, Haan MN, Levine RA, et al. Comparing SF-36 scores across three groups of 
women with different health profiles. Qual Life Res 2005;14:1251–1261. 
10. American Gastroenterological Association Technical Review on Constipation. 
Gastroenterology 2013;144:218–238. 
11. Lembo A, Camilleri M. Chronic constipation. N Engl J Med 2003;349:1360–8. 
12. Schiller LR. New and emerging treatment options for chronic constipation. Rev 
GastroenterolDisord 2004;4(suppl 2):S43–51. 
13. BockS, Wolff K, Marti L, Schmied BM, Hetzer FH. Long-term Outcome After Transanal 
Rectal Resection in Patients With Obstructed Defecation Syndrome. Dis Colon Rectum 
2013; 56: 246–252. 


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14. Laubert T,Kleemann M, RoblickUJ, Burk C, Hildebrand P, Lewejohann J,  Schloricke E, 
Bruch HP. Obstructive defecation syndrome: 19 years of experience with laparoscopic 
resection rectopexy. Tech Coloproctol (2013) 17:307–314. 
15. The AGA Institute Medical Position Panel. American Gastroenterological Association 
Medical Position Statement on Constipation. Gastroenterology 2013;144:211–217 
16. American Gastroenterological Association Technical Review on Constipation. 
Gastroenterology 2013;144:218–238 
17. Bharucha AE, Rao SSC.An Update on Anorectal Disorders for 
Gastroenterologists.Gastroenterology 2014;146:37–45 
18. Ravi K, Bharucha AE, Camilleri M, et al. Phenotypic variation of colonic motor 
functions in chronic constipation. Gastroenterology 2010;138:89–97. 
19. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med.  
1991;324:1186–94.  
20. Blasi J, Chapman ER, Linke, et al. Botulinum neurotoxin A selectively cleaves the    
synaptic protein SNAP-25. Nature. 1993;365:160–3.  
21. Scott AB, Suzuki D. Systemic toxicity of botulinum toxin by intramuscular injection in 
the monkey. Mov Disorders. 1988;3:333–5. 
22. Pasricha PJ, Ravich WJ, Hendrix TR, et al. Intrasphincteric botulinum toxin for the 
treatment of achalsia. N Engl J Med. 1995;332:774–8.  
23. Alderson K, Holds JB, Anderson RI. Botulinum induced alteration of nerve-muscle 
interactions in the human orbicularis oculi following treatment for blepharospasm. 
Neurology. 1991;41:1800–05.  
24. Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol 
Rev. 2000 Apr;80(2):717-66. 
25. Bajohrs M, Rickman C, Binz T,  Davletov B. A molecular basis underlying differences in 
the toxicity of botulinum serotypes A and E. EMBO Rep. 2004 November; 5(11): 1090–
1095.  
26. Rao SS, Tantiphlachiva K, Remes-Troche J et al. Does biofeedback therapy modulate 
anorectal (gut)-brain axis in patients with dyssynergic defecation? (abstr) 
Gastroenterology, 140 (2011), p. S-367 
27. G.P. Thomas, T.C. Dudding, G. Rahbour et al.Sacral nerve stimulation for constipation. 
Br J Surg, 100 (2013), pp. 174–181 
28. Hallan RI,Melling J., Williams NS, Waldron DJ, Morrison JFB. Treatment of anismus in 
intractable constipation with Botulinum A toxin. Lancet. 1988 Sep 24;2(8613):714-7. 
29. Faried M, El Nakeeb A, Youssef M, Omar W, El Monem HA. Comparative Study 
between Surgical and Non-surgical Treatment of Anismus in Patients with Symptoms of 
Obstructed Defecation: A Prospective Randomized Study. J Gastrointest Surg (2010) 
14:1235–1243. 
30. Maria G, Cadeddu F, Brandara F, Marniga G, Brisinda G. Experience with Type A 
Botulinum Toxin for Treatment of Outlet-Type Constipation. Am J Gastroenterol 
2006;101:2570–2575 
31. Joo JS, Agachan F, Wolff B, Nogueras JJ, Wexner SD. Initial North American 
experience with botulinum toxin type A for treatment of anismus. Dis Colon Rectum. 
1996 Oct;39(10):1107-11. 


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32. Ron Y, Avni Y, Lukovetski A, Wardi J, Geva D, Birkenfeld S, Halpern Z. Botulinum 
toxin type-A in therapy of patients with anismus. Dis Colon Rectum. 2001 
Dec;44(12):1821-6. 
33. Farid M, El Monem HA, Omar W, El Nakeeb A, Fikry A, Youssef T, Yousef M, Ghazy 
H, Fouda E, El Metwally T, Khafagy W, Ahmed S, El Awady S, Morshed M, El Lithy R. 
Comparative study between biofeedback retraining and botulinum neurotoxin in the 
treatment of anismus patients. Int J Colorectal Dis. 2009 Jan;24(1):115-20. doi: 
10.1007/s00384-008-0567-0. Epub 2008 Aug 22. 
34. Dominique El-Khawand1, 2  , Salim Wehbe1 and Kristene Whitmore1 Botulinum toxin for 
conditions of the female pelvis. Int Urogynecol J (2013) 24:1073–1081 
35. Shafik A, El-Sibai O. Botulin toxin in the treatment of nonrelaxing puborectalis 
syndrome. Dig Surg. 1998;15(4):347-51. PubMed PMID: 9845612. 
36. Hompes R, Harmston C, Wijffels N, Jones OM, Cunningham C, Lindsey I. Excellent 
response rate of anismus to botulinum toxin if rectal prolapse misdiagnosed as anismus 
('pseudoanismus') is excluded. Colorectal Dis. 2012 Feb;14(2):224-30. 
37. Zhang B, Ding JH, Zhao YJ, Zhang M, Yin SH, Feng YY, Zhao K. Midterm outcome of 
stapled transanal rectal resection for obstructed defecation syndrome: a single-institution 
experience in China. World J Gastroenterol. 2013 Oct 14;19(38):6472-8.  
38. Ohazuruike NL, Martellucci J, Menconi C, Panicucci S, Toniolo G, Naldini G.Short-term 
results after STARR versus internal Delorme for obstructed defecation:a non-randomized 
prospective study. Updates Surg. 2014 Jan 16. 
 
 
 
 
 
 
 
 
 

ICF_001.pdf: 
Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
Page 1 of 15 
 
Subject Identification 
Protocol Title: Effects of Type A botulinum toxin in obstructed defecation 
syndrome: a Phase II randomized, parallel group, triple-blind, placebo- 
controlled trial NCT02160288 
 
Principal Investigator: Liliana Bordeianou, MD, MPH      
 
Site Principal Investigator:      
 
Description of Subject Population: Subjects with constipation/ obstructive 
defecation syndrome   
 
 
About this consent form 
 
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form. 
 
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.” 
 
If you have any questions about the research or about this form, please ask us.  Taking part in 
this research study is up to you.  If you decide to take part in this research study, you must sign 
this form to show that you want to take part.  We will give you a signed copy of this form to 
keep. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This website will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this website at any time. 
 
 
 
 
 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 2 of 15 
 
Subject Identification 
Why is this research study being done? 
 
We are doing this research study to find out if Type A Botulinum Toxin (Botox) can help 
improve bowel emptying in people with Obstructed Defecation Syndrome (ODS).  We also want 
to find out if Botox is safe to inject without significant side effects. 
 
Obstructed defecation syndrome (ODS) is a very common cause of constipation. One of the most 
frequent causes of ODS is a muscle that contracts, instead of relaxing, when you try to move 
your bowels. The name of this muscle is puborectalis. This leads to complaints (symptoms) like 
constipation, straining, feeling of incomplete emptying of bowels  and the need to use your 
fingers to help you go. Traditional treatment approaches (fiber, laxatives and enemas) do not 
always help.   
 
Several small research studies have shown that Botox works in ODS and it helps improve the 
symptoms of constipation by relaxing the contracted puborectalis muscle. The goal of this study 
is to find out if this is indeed so. We also want to make sure that this injection does not lead to 
other bowel symptoms. 
 
The U.S. Food and Drug Administration (FDA) has approved Botox injection into the muscles to 
treat wrinkles, urinary incontinence, chronic headaches, upper limb spasticity, cervical dystonia, 
strabismus and spasm of the lids, but the FDA has not yet approved Botox to treat ODS. 
 
Over 150 people with ODS taking part in research studies around the world have received Botox 
so far.  Additionally many people have been treated with Botox in the anal muscles for the 
treatment of other conditions. 
 
In this study, we want to compare Botox with placebo. The placebo looks exactly like Botox, but 
contains no active ingredient.  During this study, you may get placebo instead of Botox. Placebos 
are used in research studies to see if the results are due to the study drug or other reasons. 
 
We are asking you to take part in this research study because you were diagnosed with ODS and 
which has not been resolved or managed with traditional treatments.  
 
We plan to enroll 46 people with ODS, all at Massachusetts General Hospital (MGH).  
 
 
 
 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 3 of 15 
 
Subject Identification 
How long will I take part in this research study? 
 
It will take you about 1 year and 1 month to complete this research study.  During this time, we 
will ask you to make 3  study visits to MGH. We will also ask you to fill in 5 surveys sent to you 
via mail during this study. 
 
What will happen in this research study? 
 
If you choose to take part in this research study, we will ask you to sign this consent form before 
we do any study procedures. 
 
Visit 1  
 
At this visit, we will again review the study with you and answer all questions.  If you choose to 
take part in this study, you will then sign this consent form.  Once you have signed the consent 
form, we will ask you to fill out a questionnaire. In total, this visit will take around 30 minutes.  
We will then schedule you for the procedure. 
 
Assignment to Study Group  
 
If  you qualify for the study, we will assign you by chance (like a coin toss) to the Botox group 
or the placebo group. You and the study doctor cannot choose your study group. You will have a 
1 in 2 chance of being assigned to the Botox group. 
 
You and the study doctor cannot know which study group you are in, but she can find out if 
necessary.  
 
Visit 2- Procedure 
 
This visit will take about 30 minutes. For this visit, you will come to the office.   
During this procedure, we will give you an injection of local anesthesia (a medicine to numb the 
area) followed by the injection of either the placebo or the Botox 
 
Your doctor will pass a small camera (transrectal ultrasound) through your anus to guide the 
needle into the puborectalis muscle where we want to inject Botox. Next, she will inject a long-
acting local anesthetic to numb you. This injection may hurt. After you are numb, your doctor 
will inject the Botox or placebo at three areas in the puborectalis muscle and external anal 
sphincter. This entire procedure should take less than 5 minutes.  
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 4 of 15 
 
Subject Identification 
We do not expect any side effects after this injection. To make sure you recover smoothly, we 
will watch you in the office till you recover after the injection. 
 
When the effect of the local anesthetic goes away, you may experience discomfort or pain at the 
site of the injection. The  pain will be minimal and you will likely not need pain medication.  
 
Follow -up Visit (Visit 3) 
 
Visit 3 will be scheduled one month after the procedure and it will take about 45 minutes.  At 
this visit, we will: 
• Do a physical exam 
• Ask you questions about your constipation symptoms 
• Ask questions to see if you had any side effects or health problems since your last 
visit 
• Ask you to fill out a second questionnaire with similar questions to the first 
questionnaire 
• Evaluate the treatment effects by anorectal manometry, electromyography (EMG) 
and balloon expulsion test. These are the tests you have had in the past that led to 
your diagnosis of ODS. You can take part in the study without agreeing to have 
any of these procedures done. They are optional (not required).  
 
Anorectal Manometry, Electromyography (EMG), and Balloon Expulsion Test  
 
We will ask you to have a special test that measures the function of your sphincter muscle 
(anorectal manometry). This is often done as part of the initial evaluation for ODS.  During this 
test, we will check your rectum to see if stool is present. If stool is present, we will have you do a 
Fleet’s enema in the office prior to the test. Then a small flexible plastic tube (a manometry 
catheter) is passed into your rectum through your anal sphincter. The manometry catheter is 
connected to a machine that records the contractions (squeezing movements) and relaxations of 
your rectum and anal sphincter. The test will take about 5 minutes and is not painful.  
 
The doctor  will then ask you to stay on your left side and a small sponge tipped sensor will be 
placed into your rectum (EMG). You may experience discomfort from this. We will use it to see 
whether your puborectalis muscle is able to relax.  This takes about 1 minute. 
 
Lastly, a 6 inch-long catheter is placed in the rectum and then filled with air (balloon expulsion 
test). You will be asked to sit on the toilet and try to expel the balloon.  We will time you for 5 
minutes.  You have completed the test when the balloon passes, or if 5 minutes pass.  If you do 
not pass the balloon, it will be deflated and removed at that time.   
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 5 of 15 
 
Subject Identification 
These procedures are very safe.  You may experience some slight discomfort during the test, and 
may have a small amount of bleeding before or during the test. 
 
 
Long Term Follow-up by Mail or Telephone (3, 6, and 12 months After Visit 2)  
You will be contacted by mail three times after your procedure at Visit 2.  
 
• We will mail you a home questionnaire to fill out at 3, 6 and 12 months after the 
procedure.  We will ask you to fill out and return to us these surveys. A prepaid 
envelope will be supplied with the return address on it. 
• If you do not complete the questionnaire, we will call you to follow-up and ask 
you these questions over the phone. 
 
 
After You Complete the Study 
After you complete the study, we will let you know its results as soon as they become available. 
We will refer you back to your own doctor for your ongoing medical care.  
 
If you were in the placebo group and the study showed that Botox worked for the people who 
received it, we will offer you the injection of Botox free of charge. 
 
Stopping the Study Early 
If you decide to stop taking part in the study for any reason, we will ask you to call the office of 
Lieba Savitt, N.P., at 617-643-5580. She is available Monday-Friday from  9 am-5 pm for any 
questions or concerns about this research study. She will ask you the reason why you chose to 
stop taking part in our study. Also, she will ask you to make a final study visit which will take 
about 30 minutes.  At this visit, we will: 
• Do  a physical exam 
• Ask about any side effects or health problems since your last visit 
• Give you a questionnaire to fill out 
 
Also, the study doctor may take you out of the study without your permission.  This may happen 
because: 
• The Sponsor decides to stop the study 
• You can’t make the required study visits 
• We stop doing the study for other reasons 
 
If this happens, the study doctor will explain why you need to stop taking part in the study.  We 
will ask you to come in for a final study visit as described above. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 6 of 15 
 
Subject Identification 
Review of Medical Records from Hospital Admissions or Emergency Department 
Visits 
 
MGH has an electronic system that lets your study doctors know if you are admitted to a Partners 
Hospital, or if you visit a Partners Hospital Emergency Department for any reason.  This alert 
will let the study doctors know why you are there.  We want to make sure the study doctors 
know about any possible problems or side effects you experience while you are taking part in the 
study. 
 
Use of Your Health Information 
 
The Department of General and Gastrointestinal Surgery at MGH may use health information 
that identifies you to do the research described in this form, and to do related research. This 
means research related to Botox alone or in combination with other treatments for ODS and 
constipation such as biofeedback. 
 
The Department of General and Gastrointestinal Surgery at MGH may use health information 
that no longer identifies you to do any type of research. 
 
 
What are the risks and possible discomforts from being in this research 
study? 
 
Risks of Taking Botox 
 
Botox injections are relatively safe when performed by an experienced doctor. The most 
common side effects include discomfort or pain at the injection site. We will numb you before 
the injection and also give you pain medication to make you comfortable.  
 
You will receive 100 units of Botox. If the dose is too high for you, the medication may cause 
problems such as leakage of gas or stool against you will (fecal incontinence). This is less 
common and only happens when very high doses (over 200 units of Botox) are used. Only 8 of 
151 patients (5.2%) who have received Botox and were studied experienced fecal incontinence 
and in most cases it was mild incontinence for gas. Only one out of 151 patients (0.7%) had 
incontinence for solid feces. The incontinence went away in most cases when the effect of the 
medication started to fade (within 2-3 months). Tell your doctor if you have any side effect that 
bothers you or that does not go away. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 7 of 15 
 
Subject Identification 
Although very unlikely, there is a possibility that the effect of Botox may spread to other parts of 
the body and cause botulism-like signs and symptoms. These problems can happen hours, days, 
to weeks after an injection of Botox. Call your doctor or get medical help right away if you 
have any of these problems after treatment with Botox:  
• 
Muscle weakness all over the body 
• 
Vision problems 
• 
Trouble speaking or swallowing 
• 
Trouble breathing 
• 
Loss of bladder control 
These problems could make it unsafe for you to drive a car or do other dangerous activities. 
The FDA has required that a black boxed warning, the strongest warning they require, be placed 
on the labeling for the drug. It means that medical studies indicate that the drug carries a risk of 
serious or even life-threatening side effects should the injected medication spread from the site of 
injection. 
There has not been a confirmed serious case of spread of toxin effect away from the injection site 
when Botox was used at the recommended doses for the diseases in which it is already approved 
by the FDA. 
As with any drug, an allergic reaction can occur.  Allergic reactions can be mild or more serious, 
and can even result in death.  Common symptoms of an allergic reaction are rash, itching, skin 
problems, swelling of the face and throat, or trouble breathing.  If you think you are having an 
allergic reaction, call the study doctor right away.  If you are having trouble breathing, call 911 
immediately.  
 
There may be other risks of Botox that are currently unknown. 
 
Risks to an Embryo or Fetus, or to a Breastfeeding Infant 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 8 of 15 
 
Subject Identification 
The effect of Botox on an embryo or fetus (developing baby still in the womb), or on a 
breastfeeding infant, is unknown and may be harmful.  Because of these unknown risks, women 
cannot take part in this study if they are: 
• Pregnant 
• Trying to become pregnant  
• Breastfeeding 
 
If you are a menopausal woman and have not had a period for the past 12 months or more, you 
will not need to have a pregnancy test.  Also, you will not need to have a pregnancy test if you 
have had a hysterectomy (surgical removal of your uterus and/or ovaries).  All other female 
subjects must have a negative pregnancy test before receiving Botox. 
 
For Females 
If you are sexually active female and able to become pregnant, you must agree to use one of the 
birth control methods listed below.  You must use birth control for the entire study. We 
recommend that you use two methods contraception for the first three months after your dose of 
Botox.  
 
Acceptable birth control methods for use in this study are: 
• Hormonal methods, such as birth control pills, patches, injections, vaginal 
ring, or implants 
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a 
foam, cream, or gel that kills sperm) 
• Intrauterine device (IUD) 
• Abstinence (no sex) 
 
For the first three months after the injection, we recommend that you use a barrier method in 
addition to another method. If you are unsure which method to use, ask your study doctor. 
 
If you miss a period, or think you might be pregnant during the study, you must tell the study 
doctor or nurse immediately.  If you become pregnant, you must stop taking part in the study.  
The study doctor may ask for your permission to collect information about the outcome of your 
pregnancy and the condition of your newborn.  
 
 
For Males 
If you are sexually active, and able to father a child, you must agree to use one of the birth 
control methods listed below.  You must use birth control for the entire study. We recommend 
that you use two methods contraception for the first three months after your dose of Botox.  
 
Acceptable birth control methods that you can use in this study are: 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 9 of 15 
 
Subject Identification 
• Condoms with spermicide (a foam, cream, or gel that kills sperm) 
• Abstinence (no sex) 
 
Acceptable birth control methods that your partner(s) should use are: 
• Hormonal methods, such as birth control pills, patches, injections, vaginal 
ring, or implants 
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a 
foam, cream, or gel that kills sperm) 
• Intrauterine device (IUD) 
 
For the first three months after the injection, we recommend that you use a barrier method in 
addition to another method. If you are unsure which method to use, ask your study doctor. 
 
If your female partner misses a period, or thinks she might be pregnant during the time you are in 
the study, you must tell the study doctor or nurse immediately.  The study doctor may ask for 
your partner’s permission to collect information about the outcome of her pregnancy and the 
condition of her newborn.  You will not have to stop taking part in the study if your partner 
becomes pregnant.  
 
Risks of Taking Botox with Other Medications 
 
Only about 150 adults in studies have received Botox for ODS. Botox has also been used in 
children with constipation. Botox has been injected into the anus for other reasons (anal fissures) 
in many patients, and has been injected into other sites on adults.  We don’t know about all the 
side effects that can happen when taking Botox with other drugs. 
 
Risks of  Study Injection Procedure  
We do not expect any unusual safety concerns in this study. The small foreseeable discomforts 
and complications of the office procedures have been listed with their description. 
 
We will give you an injection with a long-acting local anesthetic to numb you before injecting 
Botox. Injecting the anesthetic through your rectum may hurt. Next, we will inject Botox or 
placebo at three sites in the contracting puborectalis muscle and external anal sphincter. This 
injection may also feel uncomfortable, or even hurt. 
 
We do not expect any other complications after this injection. We will keep you in the office for 
30 minutes after the injection, to make sure you don’t experience any side effects, drowsiness or 
other immediate complications.  
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 10 of 15 
 
Subject Identification 
After the effect of the anesthetic passes, you may experience discomfort or pain at the site of the 
injection. We will give you pain medication to control it. If necessary, we can give you a 
prescription for pain medication. 
 
 
Psycho-social (non-medical) risks 
Psychosocial risks may include loss of productivity from appointments. We tried to limit the 
number of appointments you have to attend for our study to three (one for consent, one for the 
injection and one a month later). Therefore, we ask you that you agree to us contacting you by 
mail or phone to monitor the response of your disease to medication and possible side effects. 
 
You may experience frustration if your symptoms do not improve and you need to undergo 
further treatments and investigations.  
 
Some people may feel frustrated because the study doctors don’t let them see the results of their 
tests. We will share with you the results of all tests you undergo as part of this study once the 
study is over. 
 
 
What are the possible benefits from being in this research study? 
 
You may not benefit from taking part in this research study.  If you receive Botox, your 
constipation symptoms and quality of life could improve after the injection. If the results of the 
study show that Botox works and you received placebo, we will offer you a Botox injection at 
the end of the study. 
 
Other people with ODS may benefit in the future from what we learn in this study.  Only a few 
easy-to-administer and fast-acting options are available for the treatment of ODS. If Botox 
works, it could improve the suffering and discomfort caused by this condition.  
 
What other treatments or procedures are available for my condition? 
 
You do not have to take part in this research study to be treated for ODS.  Other treatments or 
procedures that are available for ODS include: 
 
1. Treatment with medication (laxatives, enemas or fiber supplements) 
2. Treatment with biofeedback therapy 
3. Surgical procedures including colostomy or illeostomy 
 
Talk with the study doctor if you have questions about any of these treatments or procedures. 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 11 of 15 
 
Subject Identification 
 
 
Can I still get medical care within Partners if I don’t take part in this 
research study, or if I stop taking part?  
 
Yes.  Your decision won’t change the medical care you get within Partners now or in the future.  
There will be no penalty, and you won’t lose any benefits you receive now or have a right to 
receive. 
 
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  We will tell you if we learn new 
information that could make you change your mind about taking part in this research study. 
 
 
What should I do if I want to stop taking part in the study? 
 
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed. 
 
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed. 
 
 
Will I be paid to take part in this research study? 
 
We will not pay you to take part in this study. 
 
 
What will I have to pay for if I take part in this research study? 
 
The Department of General and Gastrointestinal Surgery at MGH is providing the Botox and 
placebo at no cost. Study funds will pay for the injections, study visits and procedures that are 
done only for research. 
 
Although study funds will pay for the injection and study procedures, we may bill your health 
insurer for, among other things, routine items and services you would have received even if you 
did not take part in the research. You will be responsible for payment of any deductibles and co-
payments required by your insurer for your routine care or other billed care.  If you have any 
questions about costs to you that may result from taking part in the research, please speak with 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 12 of 15 
 
Subject Identification 
the study doctors and study staff.  If necessary, we will arrange for you to speak with someone in 
Patient Financial Services about these costs. 
 
 
What happens if I am injured as a result of taking part in this research 
study? 
 
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer. 
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form. 
 
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the next section of this consent form. 
 
 
If I have questions or concerns about this research study, whom can I 
call? 
 
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.
 
Dr. Liliana Bordeianou is the person in charge of this research study.  You can call her at 617-643-0541, 
Monday-Friday from  9 am-5 pm.  The MGH 24hours/day contact information is 24-hour contact: MGH: 
617-726-2000 beeper 14039. 
 
You can also call Lieba Savitt, N.P., at 617-643-5580; she is available Monday-Friday from  9 
am-5 pm for questions about this research study, including scheduling your appointments or 
study visits. She is also the person you should call if you want to withdraw from the research 
study. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 13 of 15 
 
Subject Identification 
You can also call Holly Milch, N.P., at 617-643-5580. She is available Monday-Friday from 
8am-4pm with questions about the research study, including reporting adverse effects and 
scheduling your appointments or study visits. 
 
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 617-424-4100. 
 
You can talk to them about: 
▪ 
Your rights as a research subject 
▪ 
Your concerns about the research 
▪ 
A complaint about the research 
 
Also, if you feel pressured to take part in this research study, or to continue with it, they want to 
know and can help. 
 
 
If I take part in this research study, how will you protect my privacy? 
 
During this research, identifiable information about your health will be collected.  In the rest of 
this section, we refer to this information simply as “health information.”  In general, under 
federal law, health information is private.  However, there are exceptions to this rule, and you 
should know who may be able to see, use, and share your health information for research and 
why they may need to do so. 
 
In this study, we may collect health information about you from: 
• Past, present, and future medical records 
• Research procedures, including research office visits, tests, interviews, and 
questionnaires 
 
Who may see, use, and share your identifiable health information and why they may 
need to do so: 
• Partners research staff involved in this study 
• The sponsor(s) of this study, and the people or groups it hires to help perform this 
research 
• Other researchers and medical centers that are part of this study and their ethics boards 
• A group that oversees the data (study information) and safety of this research 
• Non-research staff within Partners who need this information to do their jobs (such as for  
treatment, payment (billing), or health care operations) 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 14 of 15 
 
Subject Identification 
• The Partners ethics board that oversees the research and the Partners research quality 
improvement programs. 
• People from organizations that provide independent accreditation and oversight of 
hospitals and research 
• People or groups that we hire to do work for us, such as data storage companies, insurers, 
and lawyers 
• Federal and state agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health, and other US or foreign 
government bodies that oversee or review research)  
• Public health and safety authorities (for example, if we learn information that could mean 
harm to you or others, we may need to report this, as required by law) 
• Other:        
 
Some people or groups who get your health information might not have to follow the same 
privacy rules that we follow.  We share your health information only when we must, and we ask 
anyone who receives it from us to protect your privacy.  However, once your information is 
shared outside Partners, we cannot promise that it will remain private. 
 
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your health information. 
 
The results of this research study may be published in a medical book or journal, or used to teach 
others.  However, your name or other identifying information will not be used for these purposes 
without your specific permission. 
 
Your Privacy Rights 
 
You have the right not to sign this form that allows us to use and share your health information 
for research; however, if you don’t sign it, you can’t take part in this research study.    
 
You have the right to withdraw your permission for us to use or share your health information 
for this research study.  If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing.  Once permission is withdrawn, you cannot continue to 
take part in the study. 
 
If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template - Drug Clinical Trial 
Version Date:  February 2010 
 
 
 
 
Page 15 of 15 
 
Subject Identification 
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment.  To ask for this information, please contact the person in charge of this 
research study.  You may only get such information after the research is finished. 
 
 
Informed Consent and Authorization 
 
Statement of Study Doctor or Person Obtaining Consent 
 
▪ 
I have explained the research to the study subject. 
▪ 
I have answered all questions about this research study to the best of my ability. 
 
 
 
 
 
 
Study Doctor or Person Obtaining Consent 
Date/Time 
 
 
Statement of Person Giving Informed Consent and Authorization 
 
▪ 
I have read this consent form. 
▪ 
This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
▪ 
I have had the opportunity to ask questions. 
▪ 
I understand the information given to me.
 
 
 
Signature of Subject: 
 
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above. 
 
 
 
 
 
 
Consent Form Version Date:  11/28/2016