Non-relaxing Puborectalis SyndromePhase 2/3NCT01780636

Ultrasound and EMG Guided Botox Injection for the Treatment of Non-Relaxing Puborectalis Syndrome

A Phase 2/3 study testing botulinum toxin in people with Non-relaxing Puborectalis Syndrome, run by Karen Noblett at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Non-relaxing Puborectalis Syndrome
What is being tested?: botulinum toxin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: Jan 2013to Jul 2014
Phase: Phase 2/3
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 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female
18 years of age or older
Diagnosis of non-relaxing puborectalis syndrome

Who cannot join

Allergy or sensitivity to botulinum toxin
Pregnancy or plan to become pregnant in the subsequent 6 months after injection
Undiagnosed ano-rectal mass, lesion, or infection
Stage II or greater rectocele

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California, Irvine Medical Center
Orange, California, 92868

Other trials in United States

About this study

Our study aims to determine the efficacy of ultrasound and EMG guided Botox injections into the puborectalis muscle in women with non-relaxing puborectalis syndrome. With use of this technique, we believe we will find that Botox injections decrease symptom severity and improve quality of life (QOL) in patients with NRPS. All enrolled patients will receive ultrasound and EMG guided Botox injections at three points along the puborectalis muscle. Post-injection data will be obtained with a defecation diary and questionnaire data at the 2-week, 3-month, and 6-month intervals.

Read the detailed description

Non-relaxing puborectalis syndrome (NRPS) is an obstructive defecatory disorder that presents with chronic constipation, anismus, or a sensation of incomplete rectal emptying. The specific etiology of this syndrome is unknown. The true incidence of NRPS is unknown, but it is estimated that 4% of patients with defecatory disorders have NRPS. Previous therapies for non-relaxing PRS have included biofeedback, pelvic floor physical therapy, dietary changes, laxatives, enemas, and surgical division of the puborectalis muscle. Unfortunately, responses to these treatments have been variable at best. Direct injection of botulinum toxin (Botox) into the puborectalis muscle is an alternative approach for treating NRPS and has recently been reported in a limited number of studies. Botox blocks cholinergic nerve endings in the autonomic nervous system and has been used to weaken the puborectalis muscle in constipated patients.

Our study aims to determine the efficacy of ultrasound and EMG guided Botox injections into the puborectalis muscle in women with NRPS. With use of this technique, we believe we will find that Botox injections decrease symptom severity and improve quality of life (QOL) in patients with NRPS.

We plan to compare patient reported symptoms, symptom severity, and QOL prior to Botox injections with symptoms and QOL at 2-week, 3-month, and 6-month intervals after Botox injection into the puborectalis muscle in patients with NRPS.

All enrolled patients will receive ultrasound and EMG guided Botox injections at three points along the puborectalis muscle. Post-injection data will be obtained with a defecation diary and questionnaire data at the 2-week, 3-month, and 6-month intervals. Additional injections will be offered to patients who fail the initial treatment.

Conditions: Non-relaxing Puborectalis Syndrome
Being tested: botulinum toxin
Keywords: Non relaxing puborectalis syndrome, Botulinum toxin A, Botox, Constipation
Medical subject headings: Constipation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

botulinum toxinDrug
Also called Botox (Allergan, Irvine, CA)

Study groups in NCT01780636
Study group	Role	What they receive
Botulinum toxin (Botox) injection	Experimental	All patients will be given the active Botox injection and thus this study will remain open-label and non-randomized as this is a pilot study to determine initial efficacy. Receives: Drug: botulinum toxin

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Symptoms Based on Scores Using the PAC-SYM and Wexner Constipation Questionnaires.
To assess whether Botox injections into the puborectalis muscle will improve patient's symptoms based on scores using the PAC-SYM and Wexner Constipation validated questionnaires from baseline to 6 months post-Botox injection to determine severity of symptoms. The PAC-SYM questionnaire unabbreviated title is Patient Assessment of Constipation-Symptoms and the total score is summed ranging from 0 to 44. The Wexner Constipation questionnaire total score is summed ranging from 0 to 30. Both questionnaires have higher values representing a worse outcome.
Measured: Baseline to 6 months post-injection
PAC-SYM and Wexner Scores
Scores on a scale The baseline scores were compared to scores at 6 months to evaluate the degree of improvement
Measured: Baseline to 6 months

Secondary outcomes (1)

Change in Pressures on Anal Manometry
To assess the change in pressures on anal manometry before and after Botox injections into the puborectalis muscle from baseline to 6 months post-Botox injection. Anal manometry is a test done in clinic to assess bowel function. Average resting pressure is recorded using the advanced diagnostic equipment. Above 40 mmHg is normal for resting pressure. Also, average squeeze pressure will be recorded. Greater than 100 mmHg is normal for average squeeze pressure.
Measured: Baseline to 6 months post-injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2013Jul 2014

First posted31 Jan 2013 (estimated)
Study startJan 2013
Primary completionJan 2014
Study completionJul 2014

Why it stopped: POOR 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 (15)Papers the sponsor has linked to this study.
Other trials for Non-relaxing Puborectalis SyndromeStudies of the same condition, open and under way.
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 2/3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01780636
Sponsor's protocol ID: ALLERGAN-72570 HS# 2012-8750
Status last verified: Oct 2021
First submitted: 25 Jan 2013
Last updated: 3 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Times ML, Reickert CA. Functional anorectal disorders. Clin Colon Rectal Surg. 2005 May;18(2):109-15. doi: 10.1055/s-2005-870892.
PubMed 20011350
WASSERMAN IF. PUBORECTALIS SYNDROME (RECTAL STENOSIS DUE TO ANORECTAL SPASM). Dis Colon Rectum. 1964 Mar-Apr;7:87-98. doi: 10.1007/BF02616902. No abstract available.
PubMed 14128302
Kuijpers HC, Bleijenberg G. The spastic pelvic floor syndrome. A cause of constipation. Dis Colon Rectum. 1985 Sep;28(9):669-72. doi: 10.1007/BF02553449.
PubMed 4053909
Karlbom U, Hallden M, Eeg-Olofsson KE, Pahlman L, Graf W. Results of biofeedback in constipated patients: a prospective study. Dis Colon Rectum. 1997 Oct;40(10):1149-55. doi: 10.1007/BF02055160.
PubMed 9336109
Meunier P, Marechal JM, de Beaujeu MJ. Rectoanal pressures and rectal sensitivity studies in chronic childhood constipation. Gastroenterology. 1979 Aug;77(2):330-6.
PubMed 447047
MacDonald A, Shearer M, Paterson PJ, Finlay IG. Relationship between outlet obstruction constipation and obstructed urinary flow. Br J Surg. 1991 Jun;78(6):693-5. doi: 10.1002/bjs.1800780620.
PubMed 2070237
Mellgren A, Bremmer S, Johansson C, Dolk A, Uden R, Ahlback SO, Holmstrom B. Defecography. Results of investigations in 2,816 patients. Dis Colon Rectum. 1994 Nov;37(11):1133-41. doi: 10.1007/BF02049817.
PubMed 7956583
Wexner SD, Jorge JM. Colorectal physiological tests: use or abuse of technology? Eur J Surg. 1994 Mar;160(3):167-74.
PubMed 8003569
Halligan S, Malouf A, Bartram CI, Marshall M, Hollings N, Kamm MA. Predictive value of impaired evacuation at proctography in diagnosing anismus. AJR Am J Roentgenol. 2001 Sep;177(3):633-6. doi: 10.2214/ajr.177.3.1770633.
PubMed 11517060
Salzano A, Cavallo G, De Rosa A, De Luca LE, Serpe A, Losco M. [Diagnosis with defecography of puborectal muscle syndrome]. Radiol Med. 1997 Apr;93(4):396-400. Italian.
PubMed 9244917
Ganeshan A, Anderson EM, Upponi S, Planner AC, Slater A, Moore N, D'Costa H, Bungay H. Imaging of obstructed defecation. Clin Radiol. 2008 Jan;63(1):18-26. doi: 10.1016/j.crad.2007.05.015. Epub 2007 Sep 14.
PubMed 18068787
Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Albanese A. Botulinum toxin in the treatment of outlet obstruction constipation caused by puborectalis syndrome. Dis Colon Rectum. 2000 Mar;43(3):376-80. doi: 10.1007/BF02258305.
PubMed 10733120
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.
PubMed 17029615
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. doi: 10.1007/BF02234461.
PubMed 11742168
Shafik A, El-Sibai O. Botulin toxin in the treatment of nonrelaxing puborectalis syndrome. Dig Surg. 1998;15(4):347-51. doi: 10.1159/000018630.
PubMed 9845612

Study at a glance

From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Ultrasound and EMG Guided Botox Injection for the Treatment of Non-Relaxing Puborectalis Syndrome
ClinicalTrials.gov ID: NCT01780636
Acronym / sponsor ID: ALLERGAN-72570 HS# 2012-8750
Conditions: Non-relaxing Puborectalis Syndrome
Keywords: Non relaxing puborectalis syndrome, Botulinum toxin A, Botox, Constipation
Phase: Phase 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: POOR RECRUITMENT
Enrolment: 7 participants (actual)
Lead sponsor: Karen NoblettUniversity, hospital or other
Collaborators: American Urogynecologic Society, Allergan
Study start: Jan 2013 (actual)
Primary completion: Jan 2014 (actual)
Study completion: Jul 2014 (actual)
First posted: 31 Jan 2013 (estimated)
Results: Posted 3 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Botulinum toxin (Botox) injection	Experimental	Drug: botulinum toxinAll patients will be given the active Botox injection and thus this study will remain open-label and non-randomized as this is a pilot study to determine initial efficacy.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Female
18 years of age or older
Diagnosis of non-relaxing puborectalis syndrome

Key exclusion criteria (4 listed)

Allergy or sensitivity to botulinum toxin
Pregnancy or plan to become pregnant in the subsequent 6 months after injection
Undiagnosed ano-rectal mass, lesion, or infection
Stage II or greater rectocele

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 toxinAlso: Botox (Allergan, Irvine, CA)	Drug	Botulinum toxin (Botox) injection

Primary outcome

Change in Symptoms Based on Scores Using the PAC-SYM and Wexner Constipation Questionnaires.
Time frame: Baseline to 6 months post-injection
To assess whether Botox injections into the puborectalis muscle will improve patient's symptoms based on scores using the PAC-SYM and Wexner Constipation validated questionnaires from baseline to 6 months post-Botox injection to determine severity of symptoms. The PAC-SYM questionnaire unabbreviated title is Patient Assessment of Constipation-Symptoms and the total score is summed ranging from 0 to 44. The Wexner Constipation questionnaire total score is summed ranging from 0 to 30. Both questionnaires have higher values representing a worse outcome.
PAC-SYM and Wexner Scores
Time frame: Baseline to 6 months
Scores on a scale The baseline scores were compared to scores at 6 months to evaluate the degree of improvement

1 secondary outcome

Change in Pressures on Anal Manometry
Time frame: Baseline to 6 months post-injection

Results and safety

Results posted to the registry on 3 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Botulinum Toxin (Botox) Injection	7	7

Primary outcome: Change in Symptoms Based on Scores Using the PAC-SYM and Wexner Constipation Questionnaires.

Time frame: Baseline to 6 months post-injection

Population analysed: All females between the ages of 40-75 and data was insufficient to analyze as target enrollment was not met and terminated due to poor recruitment. The data for this outcome measure was not collected.

Primary outcome: PAC-SYM and Wexner Scores

Time frame: Baseline to 6 months

Population analysed: All 7 received Botox and data was insufficient to analyze as target enrollment was not met and terminated due to poor recruitment. The data for this outcome measure was not collected.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Botulinum Toxin (Botox) Injection	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20011350Times ML, Reickert CA. Functional anorectal disorders. Clin Colon Rectal Surg. 2005 May;18(2):109-15. doi: 10.1055/s-2005-870892.
Background: PubMed 14128302WASSERMAN IF. PUBORECTALIS SYNDROME (RECTAL STENOSIS DUE TO ANORECTAL SPASM). Dis Colon Rectum. 1964 Mar-Apr;7:87-98. doi: 10.1007/BF02616902. No abstract available.
Background: PubMed 4053909Kuijpers HC, Bleijenberg G. The spastic pelvic floor syndrome. A cause of constipation. Dis Colon Rectum. 1985 Sep;28(9):669-72. doi: 10.1007/BF02553449.
Background: PubMed 9336109Karlbom U, Hallden M, Eeg-Olofsson KE, Pahlman L, Graf W. Results of biofeedback in constipated patients: a prospective study. Dis Colon Rectum. 1997 Oct;40(10):1149-55. doi: 10.1007/BF02055160.
Background: PubMed 447047Meunier P, Marechal JM, de Beaujeu MJ. Rectoanal pressures and rectal sensitivity studies in chronic childhood constipation. Gastroenterology. 1979 Aug;77(2):330-6.
Background: PubMed 2070237MacDonald A, Shearer M, Paterson PJ, Finlay IG. Relationship between outlet obstruction constipation and obstructed urinary flow. Br J Surg. 1991 Jun;78(6):693-5. doi: 10.1002/bjs.1800780620.
Background: PubMed 7956583Mellgren A, Bremmer S, Johansson C, Dolk A, Uden R, Ahlback SO, Holmstrom B. Defecography. Results of investigations in 2,816 patients. Dis Colon Rectum. 1994 Nov;37(11):1133-41. doi: 10.1007/BF02049817.
Background: PubMed 8003569Wexner SD, Jorge JM. Colorectal physiological tests: use or abuse of technology? Eur J Surg. 1994 Mar;160(3):167-74.
Background: PubMed 11517060Halligan S, Malouf A, Bartram CI, Marshall M, Hollings N, Kamm MA. Predictive value of impaired evacuation at proctography in diagnosing anismus. AJR Am J Roentgenol. 2001 Sep;177(3):633-6. doi: 10.2214/ajr.177.3.1770633.
Background: PubMed 9244917Salzano A, Cavallo G, De Rosa A, De Luca LE, Serpe A, Losco M. [Diagnosis with defecography of puborectal muscle syndrome]. Radiol Med. 1997 Apr;93(4):396-400. Italian.
Background: PubMed 18068787Ganeshan A, Anderson EM, Upponi S, Planner AC, Slater A, Moore N, D'Costa H, Bungay H. Imaging of obstructed defecation. Clin Radiol. 2008 Jan;63(1):18-26. doi: 10.1016/j.crad.2007.05.015. Epub 2007 Sep 14.
Background: PubMed 10733120Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Albanese A. Botulinum toxin in the treatment of outlet obstruction constipation caused by puborectalis syndrome. Dis Colon Rectum. 2000 Mar;43(3):376-80. doi: 10.1007/BF02258305.
American Urogynecologic SocietyLink provided by the sponsor.

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.

Karen Noblett, MD principal investigator

University of California, Irvine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing botulinum toxin in people with Non-relaxing Puborectalis Syndrome, run by Karen Noblett 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 3 inclusion and 4 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 3 Nov 2021. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 3 Nov 2021). 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?

Change in Symptoms Based on Scores Using the PAC-SYM and Wexner Constipation Questionnaires. (time frame: Baseline to 6 months post-injection). The study lists 2 primary outcomes in all. 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 NCT01780636, which also lists 15 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 3 Nov 2021.