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

University Hospital, Rouen

Status and phase: Completed; Phase 3

Conditions: Fecal Incontinence

Treatments: Drug: Botulinum toxin A or physiologic serum injection; Procedure: Rectoscopy; Procedure: Anorectal manometry

Study type: Interventional

Funder types: Other

Identifiers

NCT02414425

2014/008/HP

2014-003650-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 200 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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200 participants in 2 patient groups, including a placebo group

Rectal Injection of Botulinum toxin A

Experimental group

Description:

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

Treatment:

Procedure: Anorectal manometry

Procedure: Rectoscopy

Drug: Botulinum toxin A or physiologic serum injection

Rectal Injection of physiologic serum

Placebo Comparator group

Description:

physiologic serum will be injected during rectoscopy for patient with rectal incontinence. Anorectal manometry will be performed for evaluation of efficacy of placebo

Treatment:

Procedure: Anorectal manometry

Procedure: Rectoscopy

Drug: Botulinum toxin A or physiologic serum injection