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

Fecal Incontinence Clinical Trial

— FI_TOXIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02414425
• Other study ID #: 2014/008/HP
• Secondary ID: 2014-003650-14
• Status: Recruiting
• Phase: Phase 3
• First received: April 1, 2015
• Last updated: December 6, 2016
• Start date: December 2015
• Est. completion date: July 2019

Study information

• Verified date: December 2016
• Source: University Hospital, Rouen
• Contact: Anne-Marie LEROI, Pr
• Email: anne-marie.leroi[@]chu-rouen.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fecal Incontinence

Intervention

Procedure:
• Rectoscopy
A rectoscopy will be performed for Botulinum toxin A or physiologic serum injection
• 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

Locations

Country	Name	City	State
France	Bordeaux University Hospital	Bordeaux
France	Clinique des Cèdres	Cornebarrieu
France	Hospices Civils de Lyon	Lyon
France	AP-HM Hôpital Nord	Marseille
France	AP-HP Hôpital Tenon	Paris
France	Hôpital des Diaconesses	Paris
France	Rennes University Hospital	Rennes
France	Rouen University Hospital	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	1 Month	No
Secondary	Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	6 Months	Yes
Secondary	Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	1 Month	Yes
Secondary	Number of Adverse Events	Imputability of Adverse events is evaluated by investigator	3 Months	Yes
Secondary	Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	6 Months	No
Secondary	Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	3 Months	No
Secondary	Change from baseline in the severity of fecal incontinence	The severity of fecal incontinence is evaluated using Cleveland Clinic Score	1 Month	No
Secondary	Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	6 Months	No
Secondary	Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	3 Months	No
Secondary	Change from baseline on delay in postponing defecation	postponing defecation delay is evaluated using a bowel diary	1 Month	No
Secondary	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	No
Secondary	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	No
Secondary	Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	6 months	No
Secondary	Change from baseline in the Number of urgencies episodes per week	The number of urgencies episodes is evaluated using a bowel diary	3 months	No