Obstructed Defecation Syndrome (ODS)Phase 2NCT02160288
Effects of Botox in Obstructed Defecation Syndrome
A Phase 2 study testing Botulinum Toxin-A and Normal Saline in people with Obstructed Defecation Syndrome (ODS), run by Massachusetts General Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Obstructed Defecation Syndrome (ODS)
- What is being tested?
- Botulinum Toxin-A and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to 11 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 9Show fewer
- 1 laxative (osmotic or stimulant) for 2 weeks
- 1 fiber supplement for one month
- And/or trial of biofeedback for at least 4 sessions
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Effects of Type A Botulinum Toxin in Obstructed Defecation Syndrome: a Phase II Randomized, Parallel-Group, Triple-Blind, Placebo-Controlled Trial
The purpose of this study is to determine if Botulinum Toxin-A (Botox) injection will improve symptoms of constipation in obstructed defecation syndrome (ODS).
Read the 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.
- Conditions
- Obstructed Defecation Syndrome (ODS)
- Being tested
- Botulinum Toxin-A, Normal Saline
- Keywords
- Botox, Obstructed Defecation Syndrome, ODS, Outlet-Type Constipation, injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin-ADrug
Also called Botox
100 Units diluted in a 5 cc syringe at a concentration of 20U/mL
Normal SalineDrug
Also called 0.9% Sodium Chloride
Dispensed in a 5 cc syringe
| Study group | Role | What they receive |
|---|---|---|
| Botulinum Toxin-A | Active comparator | 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. Receives: Drug: Botulinum Toxin-A |
| Normal saline | Placebo comparator | Patients will receive normal saline (placebo) injected in the puborectalis muscle and external anal sphincter. Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the Altomare Obstructed Defecation Syndrome- Score (ODS-S) and Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
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
Measured: Baseline, 1 month after injection
Secondary outcomes (9)
Changes in the Altomare ODS Score (ODS-S)
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.
Measured: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
Changes in the Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
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.
Measured: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
Changes in Health-Related Quality of Life
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
Measured: Baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
Changes in Cleveland Clinic Fecal Incontinence Score (CCFI)
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.
Measured: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
Changes in Fecal Incontinence Quality of Life Scale (FIQoL)
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).
Measured: Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months
Relaxation of Puborectalis With Push Measured by EMG
This is a measure of efficacy.
Measured: Baseline, 1 month follow-up visit
Success of Balloon Expulsion Test
This is a measure of efficacy.
Measured: Baseline, 1 month follow-up visit
Change in Anal Sphincter Function
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.
Measured: Baseline, 1 month follow-up visit
Change in Defecation Index
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.
Measured: Baseline, 1 month follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2014 (estimated)
- Study startFeb 2016
- Primary completion11 Jun 2019
- Study completion11 Jun 2019
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Obstructed Defecation Syndrome (ODS)Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liliana Bordeianou, Massachusetts General Hospital
- Investigators
- Liliana Bordeianou, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02160288
- Sponsor's protocol ID
- MGH2014-P-000406
- Status last verified
- May 2020
- First submitted
- 3 Jun 2014
- Last updated
- 12 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 16848807Suares 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.
PubMed 21606976American 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.
PubMed 23261064Maria 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.
PubMed 17029615
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Type A Botulinum Toxin in Obstructed Defecation Syndrome: a Phase II Randomized, Parallel-Group, Triple-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT02160288
- Acronym / sponsor ID
- MGH2014-P-000406
- Conditions
- Obstructed Defecation Syndrome (ODS)
- Keywords
- Botox, Obstructed Defecation Syndrome, ODS, Outlet-Type Constipation, injection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Feb 2016 (actual)
- Primary completion
- 11 Jun 2019 (actual)
- Study completion
- 11 Jun 2019 (actual)
- First posted
- 10 Jun 2014 (estimated)
- Results
- Posted 12 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum Toxin-A | Active comparator | Drug: Botulinum Toxin-APatients 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. |
| Normal saline | Placebo comparator | Drug: Normal SalinePatients will receive normal saline (placebo) injected in the puborectalis muscle and external anal sphincter. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin-AAlso: Botox100 Units diluted in a 5 cc syringe at a concentration of 20U/mL | Drug | Botulinum Toxin-A |
| Normal SalineAlso: 0.9% Sodium ChlorideDispensed in a 5 cc syringe | Drug | Normal saline |
Primary outcome
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
9 secondary outcomes
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
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
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
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
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
Relaxation of Puborectalis With Push Measured by EMG
Time frame: Baseline, 1 month follow-up visit
Success of Balloon Expulsion Test
Time frame: Baseline, 1 month follow-up visit
Change in Anal Sphincter Function
Time frame: Baseline, 1 month follow-up visit
Change in Defecation Index
Time frame: Baseline, 1 month follow-up visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16848807Shaheen 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.
- Background: PubMed 21606976Suares 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.
- Background: PubMed 23261064American 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.
- Background: PubMed 17029615Maria 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liliana Bordeianou, M.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Botulinum Toxin-A and Normal Saline in people with Obstructed Defecation Syndrome (ODS), run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02160288, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2020.