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

NCT01589471 | Completed Phase 2

• 1 other identifier: CE 11.088
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Low Anterior Resection Syndrome; Rectal Cancer

Keywords

Low anterior resection syndrome; Botulinum toxin A; Quality of life; Incontinence; Rectal cancer; Anorectal manometry

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

  1 month and 3 months

• Efficacy of intra-rectal Botox-A injection as documented with a patient medicine calender

  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

Study Arms (1)

Botox-A

EXPERIMENTAL

Intra-rectal (or intra-colic) injection of 100 U of Botox-A

Drug: intra-rectal Botulinum toxin A injection

Interventions

intra-rectal Botulinum toxin A injection DRUG

intra-colic injection of 100 U of Botulinum toxin A as a single injection distributed amongst the four quadrants, 5 cm above anastomosis

Also known as: Botox (Allergan)

Botox-A

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Allergan: collaborator

Study Sites (1)

Centre Hospitalier Universitaire de Montréal

Montreal, Quebec, H2X 3J4, Canada

Location

MeSH Terms

Conditions

Low Anterior Resection Syndrome; Rectal Neoplasms

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Rectal Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Carole S Richard, MD FCRSC

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 2, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 12, 2018

Record last verified: 2015-05

Locations

CA (1)