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Effects of Botox in Obstructed Defecation Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02160288
Recruitment Status : Terminated (Low recruitment)
First Posted : June 10, 2014
Results First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
Liliana Bordeianou, Massachusetts General Hospital

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).

Condition or disease Intervention/treatment Phase
Obstructed Defecation Syndrome (ODS) Drug: Botulinum Toxin-A Drug: Normal Saline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
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
Actual Study Start Date : February 2016
Actual Primary Completion Date : June 11, 2019
Actual Study Completion Date : June 11, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Changes in the Altomare Obstructed Defecation Syndrome- 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 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. ODS (altomare obstructed defecation syndrome score) scores range from 0 (minimum) to 31 (maximum) where 31 is the most severe (worse outcome) and 0 is no symptoms (better outcome).

    The scale for PAC-QoL (Patient Assessment of Constipation- Quality of life score) is a minimum of 0 and a maximum of 112 where 0 is highest quality of life (better outcome) and 112 is lowest quality of life (worse outcome)

    Larger number for change would suggest a better outcome



Secondary Outcome Measures :
  1. Changes in the Altomare ODS Score (ODS-S) [ Time Frame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months ]
    The scale title is obstructed defecation score, the minimum value is 0 and the maximum value is 31 for the ODS score. This measures the symptomatic improvement in ODS. ODS scores range from 0-31 where 31 is the most severe and 0 is no symptoms. A higher score would suggest a better outcome.

  2. Changes in the Patient Assessment of Constipation- Quality of Life Score (PAC-QoL) [ Time Frame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months ]
    PAC-QoL is Patient Assessment of Constipation- Quality of Life Score. The scale for PAC-QoL is 0 minimum score to 112 maximum score where 0 is highest quality of life (better outcome) and 112 is lowest quality of life (worse outcome). Since we are looking for a change in score, the minimum change would be 0 and the maximum change would be 112. A higher change would suggest a better outcome.

  3. Changes in Health-Related Quality of Life [ Time Frame: Baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months ]
    Medical outcomes survey short form (SF-36 version 1) will be used to measure changes in the health-related quality of life.This is a measure of efficacy. The score ranges from 0-100 where 0 is maximum impact on health and 100 is no impact on health

  4. Changes in Cleveland Clinic Fecal Incontinence Score (CCFI) [ Time Frame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months ]
    This is a measure of Botox-specific adverse events. The score is a total of answers of questions. The score range is 0-20 where 0 is perfect incontinence and 20 is complete incontinence.

  5. Changes in Fecal Incontinence Quality of Life Scale (FIQoL) [ Time Frame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months ]
    This is a measure of Botox-specific adverse events. This fecal incontinence quality of life scale (FIQoL) scale ranges from 4 as the minimum and 20 as maximum. lower score indicates lower quality of life (worse outcome) and higher score has better quality of life (better outcome).

  6. Relaxation of Puborectalis With Push Measured by EMG [ Time Frame: Baseline, 1 month follow-up visit ]
    This is a measure of efficacy.

  7. Success of Balloon Expulsion Test [ Time Frame: Baseline, 1 month follow-up visit ]
    This is a measure of efficacy.

  8. 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. The minimum score for resting sphincter pressure is 0 and the maximum is 200. The minimum squeeze pressure is 10 and the maximum is 200. The lower score is suggested of decreased tone and worse outcome, where high scores may suggest worse outcome in terms of sphincter function.

  9. 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. Scores can change from 0 (meaning no change- least effective) to 1 meaning that the change shows complete relaxation with defecation.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females 18 years or older 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:

    • 1 laxative (osmotic or stimulant) for 2 weeks
    • 1 fiber supplement for one month
    • And/or trial of biofeedback for at least 4 sessions

Exclusion Criteria:

  • Previous treatment with Botox (possible antibodies)
  • Known hypersensitivity to any of the components of the toxin
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02160288


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Liliana Bordeianou, M.D. Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Liliana Bordeianou, Massachusetts General Hospital:
Informed Consent Form  [PDF] November 28, 2016

Publications:
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Responsible Party: Liliana Bordeianou, Assistant Professor of Surgery, Division of General and Gastrointestinal Surgery, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02160288    
Other Study ID Numbers: MGH2014-P-000406
First Posted: June 10, 2014    Key Record Dates
Results First Posted: May 12, 2020
Last Update Posted: May 12, 2020
Last Verified: May 2020
Keywords provided by Liliana Bordeianou, Massachusetts General Hospital:
Botox
Obstructed Defecation Syndrome
ODS
Outlet-Type Constipation
injection
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents