Effect and Tolerance of Botulinum A Toxin Rectal Injections on Fecal Incontinence (FI_TOXIN)

Effect And Tolerance of Botulinum A Toxin Rectal Injections on Fecal Incontinence

Fecal incontinence is a frequent pathology which concerns 10% of the general population and severely alters patients quality of life. The cost of urinary and faecal incontinence has been estimated to be $16 billions a year. Several treatments exist depending on the aetiology of the faecal incontinence: medical treatments, biofeedback and sacral nerve stimulation. Nevertheless, these treatments are not always effective (50-70% of success) and are not without side effects, particularly the sacral nerve stimulation (pain, infection, electrode displacement..).

The intravesical injections of botulinum toxin have been used for several years for the treatment of urinary incontinence with overactive bladder. Several randomized trials have demonstrated the efficacy of these injections in patients with neurological disorders and overactive bladder, as well as in idiopathic overactive bladder. The toxin injections in the detrusor muscle increase the compliance and the bladder capacity and delay the initial appearance of detrusor uninhibited contraction. Furthermore, botulinum toxin decreases the urinary urgency. It maybe secondary to the reduction of the amplitude of the detrusor uninhibited contraction as well as to a direct effect of toxin on sensory pelvic nerve afferents.

The botulinum toxin should play a role on motor afferents as well as on the sensory function of efferent nerves.

The hypothesis is to demonstrate a decrease of active faecal incontinence and/or urgency episodes with improvement in quality of life, without any major side effects, in the patients included in this study. Nevertheless, the benefit of toxin injections are known to be temporary because of nerve re-growth. If we obtain similar results for fecal incontinence, it would be possible to schedule one to two injections a year because of the limited side-effects and invasiveness of the rectal injections.

Study Overview

• Status: Unknown
• Conditions: Fecal Incontinence
• Intervention / Treatment: Procedure: Rectoscopy; Procedure: Anorectal manometry; Drug: Botulinum toxin A or physiologic serum injection

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anne-Marie LEROI, Pr; Email: anne-marie.leroi@chu-rouen.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • Bordeaux University Hospital
    • Contact: Franck ZERBIB, Pr
  • Cornebarrieu, France
    • Recruiting
    • Clinique des Cèdres
    • Contact: Michel QUERALTO, MD
  • Lyon, France
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: François MION, Pr
  • Marseille, France
    • Recruiting
    • AP-HM Hôpital Nord
    • Contact: Véronique VITTON, MD
  • Paris, France
    • Recruiting
    • AP-HP Hôpital Tenon
    • Contact: Gérard AMARENCO, Pr
  • Paris, France
    • Recruiting
    • Hôpital des Diaconesses
    • Contact: Isabelle ETIENNEY, MD
  • Rennes, France
    • Recruiting
    • Rennes University Hospital
    • Contact: Laurent SIPROUDHIS, Pr
  • Rouen, France, 76031
    • Recruiting
    • ROUEN university hospital
    • Contact: Anne-Marie LEROI, Pr; Email: anne-marie.leroi@chu-rouen.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with at least one episode of active Fecal Incontinence and /or urgency per week;
• Patients with Fecal Incontinence for at least 3 months;
• Patients with Fecal Incontinence refractory to conventional treatment (medical and biofeedback);
• Patients having read the information letter and signed informed consent;
• Patients with medical insurance.

Exclusion Criteria:

• Patients younger than 18 years old;
• Pregnant or breast-feeding women or women without effective contraception and of age to procreate;
• Exclusive passive Fecal Incontinence;
• Fecal Incontinence secondary to anorectal malformation, post-surgery, anorectal organic disease (cancer, inflammatory bowel disease, post-radiotherapy etc.), constipation, an anal sphincter lesion which could be repaired as a first step, a rectal prolapse (the inclusion in the study is possible if Fecal Incontinence persists after rectopexy, a neurological disease with rapid progress ( stable neurological status is needed for at least 6 months);
• Patients under guardianship.
• Known Hypersensibility to botulinum toxin;
• Neuromuscular junction pathology (myasthenia, Lambert-Eaton syndrome);
• Anesthesia performed less than 1 month previously;
• Association with antibiotics
• Neurological pathology such as polyradiculoneuropathy;
• Dysphagia, pneumopathy secondary to dysphagia;
• Botulinum toxin injections during the 3 months before the beginning of the study;
• Known Hypersensitivity to albumin;
• History of inhalation pneumopathy.
• Rectoscopy impossible (anal stenosis for example);
• Anti-coagulant or anti-platelet drug or hemostasis disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rectal Injection of Botulinum toxin A; Botulinum toxin A will be injected during rectoscopy for patient with rectal incontinence. Anorectal manometry will be performed for evaluation of efficacy of experimental drug	Procedure: Rectoscopy; A rectoscopy will be performed for Botulinum toxin A or physiologic serum injection; Procedure: Anorectal manometry; Anorectal manometry will be performed to evaluate efficacy of Botulinum toxin A or physiologic serum rectal injection; Drug: Botulinum toxin A or physiologic serum injection; Botulinum toxin A or physiologic serum injection is performed during rectoscopy
Placebo Comparator: Rectal Injection of physiologic serum; physiologic serum will be injected during rectoscopy for patient with rectal incontinence. Anorectal manometry will be performed for evaluation of efficacy of placebo	Procedure: Rectoscopy; A rectoscopy will be performed for Botulinum toxin A or physiologic serum injection; Procedure: Anorectal manometry; Anorectal manometry will be performed to evaluate efficacy of Botulinum toxin A or physiologic serum rectal injection; Drug: Botulinum toxin A or physiologic serum injection; Botulinum toxin A or physiologic serum injection is performed during rectoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Number of active fecaI incontinence episodes per week	The number of fecaI incontinence episodes is evaluated using a bowel diary	1 Month
Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	1 Month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	6 Months
Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	1 Month
Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	3 Months
Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	6 Months
Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	3 Months
Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	1 Month
Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	6 Months
Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	3 Months
Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	1 Month
Change from baseline in the Number of active fecaI incontinence episodes per week	The number of fecaI incontinence episodes and/or urgencies is evaluated using a bowel diary	6 months
Change from baseline in the Number of active fecaI incontinence episodes per week	The number of fecaI incontinence episodes and/or urgencies is evaluated using a bowel diary	3 months
Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	6 months
Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	3 months

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: Anne-Marie LEROI, Pr, ROUEN university hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 6, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Botulinum Toxin A; Fecal Incontinence; Rectal injection
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Fecal Incontinence; 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: 2014/008/HP; 2014-003650-14 (EudraCT Number)