Mechanisms of Action on Rectal Motricity of Intrarectal Botulinum Toxin Injections — MECA-TOX  

Fecal Incontinence Clinical Trial

Official title: Mechanisms of Action on Rectal Motricity of Intrarectal Botulinum Toxin Injections in Patients With Fecal Incontinence

Status Not yet recruiting

Clinical Trial Summary

Previous studies have demonstrated the efficacy of this treatment in certain patients suffering from fecal incontinence, but it is not yet reimbursed in this indication as it is still in the evaluation phase. Indeed, little is known about botulinum toxin mechanisms of action. The aim of this study is to better understand the mechanisms of action of intra-rectal botulinum toxin injections, so that the investigators can identify the patients most likely to benefit from this treatment in the future.

Clinical Trial Description

Fecal incontinence is a common condition, affecting around 5 to 6% of general population. Although not a serious condition, it severely impairs quality of life and leads to social isolation. Fecal incontinence also has a significant medico-economic cost. When first-line medical treatments fail (transit-regulating therapies, perineal re-education), fecal incontinence patients can be offered treatment with sacral nerve neuromodulation. However, this therapy will only be effective in the long term, and in terms of intention to treat, in less than half of patients who have had the device definitively implanted. Today, no other treatments are available apart from sphincter repair, for which the indications are very limited, or colostomy.

The investigator's team has therefore developed another therapeutic option, intra-rectal injections of botulinum toxin, in patients suffering from active fecal incontinence (i.e., preceded by defecatory urgency). The investigator have conducted two pilot studies, which demonstrated the efficacy of this treatment in an open-label setting, and the investigator are currently completing a randomized, double-blind, controlled study to confirm its efficacy (PHRCN 2014-003650-14). Nevertheless, the mechanisms of action of intra-rectal botulinum toxin injections remain hypothetical. By analogy with the intra-detrusor injections used for over 20 years to treat overactive bladder disease, it is possible that the toxin plays an inhibitory role on rectal motricity. Botulinum toxin inhibits the release of acetylcholine at the neuromuscular junction. Without this release, smooth muscle contraction cannot take place. In one of the two pilot, intra-rectal injections of botulinum toxin were performed in 6 patients with fecal incontinence and hyperactivity of the rectum or colonic reservoir after resection. In addition to the clinically demonstrated effect of these injections, there was a significant reduction in the amplitude of rectal contractions after injection. However, there was no correlation between the observed motor effect of botulinum toxin and the efficacy of the injections. Moreover, some patients did not exhibit colonic or rectal hypermotricity and still benefited from the injections. The investigator would like to continue exploring the motor effect of intra-rectal toxin injections on a larger group of patients suffering from faecal incontinence, using a more powerful motor recording system than anorectal manometry.

For this work, we hypothesize that intra-rectal botulinum toxin injections act primarily via a motor effect by inhibiting propagated rectal contractions. To test this hypothesis, a high-resolution recto-sigmoid manometry probe will be used to evaluate rectal and sigmoidal motricity spontaneously and in response to stimulant laxative injection, before and after intra-rectal injection of botulinum toxin. Patients included will be those suffering from faecal incontinence who have failed conservative treatments and are candidates for intra-rectal injections of botulinum toxin. ;

Related Conditions & MeSH terms

• Fecal Incontinence

• NCT number: NCT05998187
• Study type: Interventional
• Source: University Hospital, Rouen
• Contact: Charlotte DESPREZ
• Phone: 0232888039
• Email: charlotte.desprez@chu-rouen.fr
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: December 1, 2023
• Completion date: December 1, 2027