Mechanisms of action on rectal motility of intrarectal botulinum toxin injections in patients with fecal incontinence - MECA-TOX

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Mar 2025 → ongoing

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515256-21-00

EudraCT number

2022-003817-12

ClinicalTrials.gov

NCT05998187

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To study, 1 month after intra-rectal injections, the effect of botulinum toxin on rectal motricity stimulated by laxative instillation and recorded in high colic resolution manometry

Secondary objectives 3

1. Evaluate the clinical efficacy of botulinum toxin injections at 1 month after injections
2. Evaluate the quality of life at 1 month after the injections
3. Evaluate the tolerance of botulinum toxin injections

Conditions and MedDRA coding

Fecal incontinence

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Active or predominantly active fecal incontinence with failure of 1st-line conservative treatments (normalization of transit, perineal re-education)
2. Impairment of quality of life at investigator's discretion
3. Patients at least 18 years of age
4. Patients who have read and understood the information letter and signed the consent form
5. Patients affiliated to the French Social Security system
6. Women: of childbearing age (defined by CTCG guidelines as fertile, after menarche and up to menopause, except in cases of permanent sterility (including hysterectomy, bilateral salpingectomy or bilateral oophorectomy) :  using effective contraception according to CTCG guidelines (progestin-only hormonal contraception for which ovulation inhibition is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) for at least 1 month prior to inclusion and for the duration of the study And,  with a negative urine pregnancy test by -HCG at inclusion and for the duration of the study.
7. Women: menopausal: menopause according to CTCG guidelines is defined as the absence of menses for 12 months without any other medical cause. An elevated level of follicle-stimulating hormone (FSH) in the post-menopausal interval in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months' amenorrhea, a single FSH measurement is insufficient.

Exclusion criteria 19

1. Pregnant women, women in labor, breastfeeding women, or women without proven contraception
2. Patient deprived of liberty by administrative or judicial decision, or protected adult (under guardianship or trusteeship)
3. Exclusive passive fecal incontinence
4. Patient suffering from constipation (Rome IV criteria)
5. Patient with an evolving inflammatory or cancerous digestive pathology
6. Previous rectal surgery
7. Person participating in another research protocol or having participated in another research protocol in the 4 weeks preceding the inclusion visit
8. Hypersensitivity to botulinum toxin or to one of the excipients (human albumin, sodium chloride)
9. Neuromuscular junction pathology (myasthenia, Lambert-Eaton syndrome, etc.)
10. Presence of infection at injection site(s)
11. General anesthesia less than one month ago
12. Association with aminoglycosides and anti-cholinesterase agents (risk of increased toxin effects)
13. History of neurogenic damage such as polyradiculoneuritis
14. History of dysphagia with esophageal or neurological stasis, swallowing disorders, inhalation pneumonitis
15. Botulinum toxin injections in the 3 months preceding the study
16. Clinical anal examination suggestive of anorectal abscess
17. Recent history (<12 months) of myocardial infarction and/or rhythm disorders not reduced by appropriate treatment
18. Peripheral motor neuropathies (such as amyotrophic lateral sclerosis or motor neuropathy) and underlying neurological disorders
19. Current treatment with anticoagulants or anti-aggregants or haemostasis disorders according to recommendations (SFED (Société Française d'endoscopie Digestive)). When patients are on anticoagulant or anti-aggregant therapy, the type of injections to be performed depends on the type of anticoagulation and the patient's thrombo-embolic risk: - Patients on anticoagulant or anti-aggregant therapy with a major thrombo-embolic risk will not be included. - Patients on anticoagulant or anti-aggregant therapy with a moderate or low thrombo-embolic risk may be included. If patients are taking a vitamin K antagonist, treatment will be continued provided that the INR is within the usual range of 2 to 3 (GETED, HAS, 2008). If patients are taking anti-aggregants, these can be continued (SFED, HAS, 2012). If patients are taking new oral anticoagulants, they should take a short break and not take the AOD the evening before or the morning of the injections (GIHP, 2015).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint was the time to onset of high amplitude propagative contractions (HAPC) after instillation of DULCOLAX® in the sigmoid and rectum, before and 1 month after intra-rectal botulinum toxin injections.

Secondary endpoints 5

1. The characteristics of the contractions at the level of the rectum and the sigmoid measured before then 1 month after injections of botulinum toxin: number, frequency, amplitude, duration of the HAPC, index of contractility, number and characteristics of the contractions (propagated or retropropagated).
2. Expulsion or not of the probe (which is an indirect sign of the efficiency of the colorectal motricity) as well as the delay of expulsion of the probe.
3. Severity scores (Cleveland Score, Appendix 2), stool schedule and quality of life score (FIQL Score, Appendix 4) before and 1 month after botulinum toxin injections.
4. Adverse events, which will be collected at each visit
5. The quality of life score (FIQL Score, Appendix 4) before and 1 month after botulinum toxin injections.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

MALLET David

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

MALLET David

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications