Effects of Botox in Obstructed Defecation Syndrome
|Obstructed Defecation Syndrome (ODS)||Drug: Botulinum Toxin-A Drug: Normal Saline||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effects of Type A Botulinum Toxin in Obstructed Defecation Syndrome: a Phase II Randomized, Parallel-Group, Triple-Blind, Placebo-Controlled Trial|
- Changes in the Altomare ODS score (ODS-S) and Patient Assessment of Constipation- Quality of Life score (PAC-QoL) [ Time Frame: Baseline, 1 month after injection ]The primary outcome measure will be the percent change from baseline in the sum of ODS-S and PAC-QoL at 1 month after the Botox injection. This measures the symptomatic improvement in ODS.
- Changes in the Altomare ODS score (ODS-S) [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection ]This is a measure of efficacy.
- Changes in the Patient Assessment of Constipation- Quality of Life score (PAC-QoL) [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection ]This is a measure of efficacy.
- Changes in Health-Related Quality of Life [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection ]SF-36 version 1 will be used to measure changes in the health-related quality of life.This is a measure of efficacy.
- Changes in Cleveland Clinic Fecal Incontinence Score (CCFI) [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection ]This is a measure of Botox-specific adverse events.
- Changes in Fecal Incontinence Quality of Life Scale (FIQoL) [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection ]This is a measure of Botox-specific adverse events.
- Relaxation of puborectalis with push measured by EMG [ Time Frame: Baseline, 1 month follow-up visit ]This is a measure of efficacy.
- Success of balloon expulsion test [ Time Frame: Baseline, 1 month follow-up visit ]This is a measure of efficacy.
- Change in anal sphincter function [ Time Frame: Baseline, 1 month follow-up visit ]The changes in anal sphincter function will be assessed by anorectal manometry. This test will measure the resting sphincter pressure, maximal resting anal pressure, maximum squeeze pressure. The change in anal sphincter function is a measure of treatment efficacy.
- 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.
|Study Start Date:||February 2016|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Botulinum Toxin-A
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.
Drug: Botulinum Toxin-A
100 Units diluted in a 5 cc syringe at a concentration of 20U/mL
Other Name: Botox
Placebo Comparator: Normal saline
Patients will receive normal saline (placebo) injected in the puborectalis muscle and external anal sphincter.
Drug: Normal Saline
Dispensed in a 5 cc syringe
Other Name: 0.9% Sodium Chloride
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02160288
|Contact: Liliana Bordeianou, M.D.||email@example.com|
|Contact: Lieba Savitt, N.P.||617-643-5580||MGHpelvicfloorcenter@partners.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Liliana Bordeianou, M.D. 617-643-0541 firstname.lastname@example.org|
|Contact: Lieba Savitt, N.P. 617-643-5580 MGHpelvicfloorcenter@partners.org|
|Principal Investigator: Liliana Bordeianou, M.D.|
|Principal Investigator:||Liliana Bordeianou, M.D.||Massachusetts General Hospital|