The Value of Botox-A for Management of Low Anterior Resection Syndrome

The Value of Botox-A Administered as a Single Intra-rectal Injection for the Management of Low Anterior Resection Syndrome: A Phase II Study

Low anterior resection syndrome (LARS) is frequent after treatment for low rectal cancer. Increased bowel frequency and urgency with rectal spasms and incontinence have deleterious impacts on quality of life in a third of the cases.

One possible physiopathology hypothesis suggests an ongoing spastic process; different mechanisms have been postulated. These include alteration of normal anorectal sensation with loss of the recto-anal inhibitory reflex (RAIR), decreased rectal compliance and reduced rectal capacity as well as sphincter damage secondary to preoperative chemoradiation therapy or during surgery.

Current available treatments are often ineffective, highlighting the need for more successful management. Botulinum toxin A (BTX-A) is a neurotoxin inhibiting acetylcholine release at the neuromuscular junction. It is currently used for the treatment of various smooth muscle spastic diseases.

The hypothesis of this study is that intra-rectal BTX-A injections could represent a medical treatment alternative for LARS. The goal of this study is to document the effects of intra-rectal BTX-A injections on sphincter function and quality of life of patients with LARS.

Study Overview

• Status: Completed
• Conditions: Low Anterior Resection Syndrome; Rectal Cancer
• Intervention / Treatment: Drug: intra-rectal Botulinum toxin A injection

Detailed Description

No more information desired

• Study Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Centre hospitalier universitaire de Montréal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• Aptitude to sign informed consent
• Diagnosis of low anterior resection syndrome (LARS) : More than 12 months after sphincter-preserving surgery for treatment of locally advanced rectal cancer, Mild to moderate underwear soiling, Baseline Wexner score ranging from 0-16 (moderate symptoms, and Patient-reported imperious defecation or Patient-reported incomplete stool evacuation
• Digital rectal exam (by surgeon) demonstrating satisfying anorectal tonus considering prior radical rectal surgery.
• Willingness to complete questionnaires and manometric studies before and after Botox-A administration
• Prior failed medical treatment, at least one attempt (narcotics, loperamide, cholestyramine, fibers)

Exclusion Criteria:

• Inability to sign informed consent
• Counter-indication to Botox-A administration : Allergy to Botox-A or its ingredients (Clostridium botulinum type A neurotoxin complex, human albumin and sodium chloride, Allergy to other forms of botulinum toxin (Dysport, Xeomin or Myobloc, Myasthenia gravis, Eaton-Lambert syndrome, lateral amyotrophic sclerosis or any other neurological disease which might interfere with neuromuscular function
• Prior use of any form of botulinum toxin A, for any indication
• Infection at proposed Botox-A injection site
• Personal or family history of bleeding diathesis
• Pregnancy or breastfeeding
• Severe incontinence (Wexner score ≥ 17 or daily use of diapers)
• Patient taking anticoagulant. ASA ( acetylsalicylic acid) allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botox-A; Intra-rectal (or intra-colic) injection of 100 U of Botox-A	Drug: intra-rectal Botulinum toxin A injection; intra-colic injection of 100 U of Botulinum toxin A as a single injection distributed amongst the four quadrants, 5 cm above anastomosis; Other Names: Botox (Allergan)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of intra-rectal Botox-A injection on anorectal function as documented with standardized Wexner score	1 month
Efficacy of intra-rectal Botox-A injection on anorectal function as documented with standardized Wexner score	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of intra-rectal Botox-A injection on anorectal function as documented with a visual scale for tenesmus and completeness of stool evacuation		1 month and 3 months
Efficacy of intra-rectal Botox-A injection on quality of life as documented with EORTC-QlQ standardized questionnaires	EORTC-QIQ is a quality of life questionnaire	1 month and 3 months
Efficacy of intra-rectal Botox-A injection as documented with a patient medicine calender	patient-filled calender for usage of any medication intended for symptomatic treatment of LARS	1 month
Efficacy of intra-rectal Botox-A injection on anorectal function as documented with standardized anorectal manometry readings		1 month
Long term efficacy of intra-rectal Botox-A injection on anorectal function as documented with Wexner score, EORTC-QLQ questionnaire and visual scale		6 months
Safety of intra-rectal Botox-A injections as documented with adverse events monitoring		1 month, 3 months and 6 months

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Allergan
• Investigators: Principal Investigator: Carole S Richard, MD FCRSC, Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: April 30, 2012
• First Posted (Estimate): May 2, 2012

Study Record Updates

• Last Update Posted (Actual): February 12, 2018
• Last Update Submitted That Met QC Criteria: February 9, 2018
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Low anterior resection syndrome; Botulinum toxin A; Quality of life; Incontinence; Rectal cancer; Anorectal manometry
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Syndrome; Rectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: CE 11.088

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No