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

Study Overview
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Brief Summary
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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.

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

Conditions
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Fecal Incontinence

Intervention / Treatment
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* Procedure: Rectoscopy
* Procedure: Anorectal manometry
* Drug: Botulinum toxin A or physiologic serum injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rectal Injection of Botulinum toxin A<br>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<br>* A rectoscopy will be performed for Botulinum toxin A or physiologic serum injection<br>Procedure: Anorectal manometry<br>* Anorectal manometry will be performed to evaluate efficacy of Botulinum toxin A or physiologic serum rectal injection<br>Drug: Botulinum toxin A or physiologic serum injection<br>* Botulinum toxin A or physiologic serum injection is performed during rectoscopy<br>|
| Placebo Comparator: Rectal Injection of physiologic serum<br>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<br>* A rectoscopy will be performed for Botulinum toxin A or physiologic serum injection<br>Procedure: Anorectal manometry<br>* Anorectal manometry will be performed to evaluate efficacy of Botulinum toxin A or physiologic serum rectal injection<br>Drug: Botulinum toxin A or physiologic serum injection<br>* Botulinum toxin A or physiologic serum injection is performed during rectoscopy<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Incontinence, Botulinum Toxin A, Rectal injection