Clinical trial NCT02160288: Effects of Botox in Obstructed Defecation Syndrome
Official title: Effects of Type A Botulinum Toxin in Obstructed Defecation Syndrome: a Phase II Randomized, Parallel-Group, Triple-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Obstructed Defecation Syndrome (ODS)
Keywords: Botox
Obstructed Defecation Syndrome
ODS
Outlet-Type Constipation
injection
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2014-06-10
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Changes in the Altomare Obstructed Defecation Syndrome- Score (ODS-S) and Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
timeFrame: Baseline, 1 month after injection
Secondary outcomes:
measure: Changes in the Altomare ODS Score (ODS-S)
timeFrame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
measure: Changes in the Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
timeFrame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
measure: Changes in Health-Related Quality of Life
timeFrame: Baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
measure: Changes in Cleveland Clinic Fecal Incontinence Score (CCFI)
timeFrame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
measure: Changes in Fecal Incontinence Quality of Life Scale (FIQoL)
timeFrame: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
measure: Relaxation of Puborectalis With Push Measured by EMG
timeFrame: Baseline, 1 month follow-up visit
measure: Success of Balloon Expulsion Test
timeFrame: Baseline, 1 month follow-up visit
measure: Change in Anal Sphincter Function
timeFrame: Baseline, 1 month follow-up visit
measure: Change in Defecation Index
timeFrame: Baseline, 1 month follow-up visit
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Liliana Bordeianou, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shaheen NJ, Hansen RA, Morgan DR, Gangarosa LM, Ringel Y, Thiny MT, Russo MW, Sandler RS. The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol. 2006 Sep;101(9):2128-38. doi: 10.1111/j.1572-0241.2006.00723.x. Epub 2006 Jul 18.
citation: Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011 Sep;106(9):1582-91; quiz 1581, 1592. doi: 10.1038/ajg.2011.164. Epub 2011 May 24.
citation: American Gastroenterological Association; Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013 Jan;144(1):211-7. doi: 10.1053/j.gastro.2012.10.029. No abstract available.
citation: 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 Nov;101(11):2570-5. doi: 10.1111/j.1572-0241.2006.00791.x. Epub 2006 Oct 4.