Intra-rectal Botulinum Toxin Injection for Intractable Non-retentive Fecal Incontinence in Children - an Open Label Pilot Study

NCT06785844 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: Intra-rectal Botulinum toxin
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Fecal Incontinence (FI) is a frustrating and prevalent GI condition with profound social implications and a marked effect on quality of life. Treatment options are limited for children whose FI is not secondary to constipation (overflow incontinence), and they are defined as having non-retentive fecal incontinence (NRFI). Rectal botulinum injections (RBI) have recently shown promise for the treatment of FI in adults, following a large, randomized placebo-controlled trial, but no data exists regarding efficacy in children. Objectives: To evaluate the efficacy and safety of RBI in children with non-retentive fecal incontinence. Methods: A prospective open-label pilot study. Children with intractable NRFI will be screened using anorectal manometry and a colonic transit study. Eligible patients will receive one course of RBI and data regarding FI frequency will be prospectively collected during a 15-week period. Significance: New treatment options for children with intractable fecal incontinence are highly in need. The current study aims to introduce a new treatment modality into pediatric research and patient care.

Conditions

Fecal Incontinence

Outcome Measures

Primary Outcomes (1)

• median number of FI episodes/week at 1-month post-intervention compared to baseline

  median number of FI episodes/week at 1-month post-intervention compared to baseline. The median FI episodes/week will be calculated based on the 21-day diary. FI episode minimal definition: any episode of soiling requiring change of underwear/clothes/washing-up.

  3-months post-intervention

Secondary Outcomes (6)

• Median number of FI episodes/week at 3-months post-intervention, compared to baseline diary.

  3-months post-intervention

• Rate of patients with a 50% decrease in mean FI episodes/week compared to baseline diary.

  3-months post-intervention

• Rate of patients with daily FI episodes (at least 1 episode/day) compared to baseline.

  3-months post-intervention

• Mean number of complete bowel movements/week compared to baseline according to diary.

  3-months post-intervention

• Parents and patient's general impression of the treatment using the following questions: "Was the treatment useful/beneficial?"; "Did the treatment improve your quality of life"?

  3-months post-intervention

Study Arms (1)

Botulinum toxin

EXPERIMENTAL

Drug: Botulinum Toxin A (Botox )

Interventions

Botulinum Toxin A (Botox ) DRUG

Botulinum Toxin injection

Botulinum toxin

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children 4-18 years old with fecal incontinence for a period greater than 6 months.
• FI frequency of ≥ 3 episodes/week.
• After appropriate medical evaluation, FI cannot be explained by another medical condition.
• Normal colonic transit study, defined as passage of 80% of markers on day
• Normal RAIR on anorectal manometry

You may not qualify if:

• Patients currently fulfilling rome IV criteria for functional constipation.
• Patients with evidence of fecal retention.
• Patients who had had good response to treatment for overflow incontinence.
• Absent RAIR on anorectal manometry.
• Any radiologic evidence of dochylosigmoid or distended colon.
• Any known organic condition that may affect bowel transit.

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

Related Publications (13)

• Rybak A, Martinelli M, Thapar N, Van Wijk MP, Vandenplas Y, Salvatore S, Staiano A, Benninga MA, Borrelli O. Colonic Function Investigations in Children: Review by the ESPGHAN Motility Working Group. J Pediatr Gastroenterol Nutr. 2022 May 1;74(5):681-692. doi: 10.1097/MPG.0000000000003429. Epub 2022 Feb 24.

  PMID: 35262513 BACKGROUND

• Athanasakos E, Cleeve S, Thapar N, Lindley K, Perring S, Cronin H, Borrelli O, Mutalib M. Anorectal manometry in children with defecation disorders BSPGHAN Motility Working Group consensus statement. Neurogastroenterol Motil. 2020 Jun;32(6):e13797. doi: 10.1111/nmo.13797. Epub 2020 Jan 27.

  PMID: 31989766 BACKGROUND

• Pascual-Pascual SI, Pascual-Castroviejo I. Safety of botulinum toxin type A in children younger than 2 years. Eur J Paediatr Neurol. 2009 Nov;13(6):511-5. doi: 10.1016/j.ejpn.2008.10.006. Epub 2008 Nov 25.

  PMID: 19036619 BACKGROUND

• Halleran DR, Lu PL, Ahmad H, Paradiso MM, Lehmkuhl H, Akers A, Hallagan A, Bali N, Vaz K, Yacob D, Di Lorenzo C, Levitt MA, Wood RJ. Anal sphincter botulinum toxin injection in children with functional anorectal and colonic disorders: A large institutional study and review of the literature focusing on complications. J Pediatr Surg. 2019 Nov;54(11):2305-2310. doi: 10.1016/j.jpedsurg.2019.03.020. Epub 2019 Apr 23.

  PMID: 31060739 BACKGROUND

• Leroi AM, Queralto M, Zerbib F, Siproudhis L, Vitton V, Amarenco G, Etienney I, Mion F, Bridoux V, Philip J, Brochard C, Damon H, Lacroix E, Gillibert A, Gourcerol G. Intrarectal injections of botulinum toxin versus placebo for the treatment of urge faecal incontinence in adults (FI-Toxin): a double-blind, multicentre, randomised, controlled phase 3 study. Lancet Gastroenterol Hepatol. 2024 Feb;9(2):147-158. doi: 10.1016/S2468-1253(23)00332-1. Epub 2023 Dec 18.

  PMID: 38128556 BACKGROUND

• Kaul A, Garza JM, Connor FL, Cocjin JT, Flores AF, Hyman PE, Di Lorenzo C. Colonic hyperactivity results in frequent fecal soiling in a subset of children after surgery for Hirschsprung disease. J Pediatr Gastroenterol Nutr. 2011 Apr;52(4):433-6. doi: 10.1097/MPG.0b013e3181efe551.

  PMID: 21240024 BACKGROUND

• Vriesman MH, Koppen IJN, Camilleri M, Di Lorenzo C, Benninga MA. Management of functional constipation in children and adults. Nat Rev Gastroenterol Hepatol. 2020 Jan;17(1):21-39. doi: 10.1038/s41575-019-0222-y. Epub 2019 Nov 5.

  PMID: 31690829 BACKGROUND

• de Bruijn CMA, Safder S, Rolle U, Mosiello G, Marshall D, Christiansen AB, Benninga MA. Development of a Bowel Management Scoring Tool in Pediatric Patients with Constipation. J Pediatr. 2022 May;244:107-114.e1. doi: 10.1016/j.jpeds.2022.01.036. Epub 2022 Feb 1.

  PMID: 35114289 BACKGROUND

• Koppen IJ, von Gontard A, Chase J, Cooper CS, Rittig CS, Bauer SB, Homsy Y, Yang SS, Benninga MA. Management of functional nonretentive fecal incontinence in children: Recommendations from the International Children's Continence Society. J Pediatr Urol. 2016 Feb;12(1):56-64. doi: 10.1016/j.jpurol.2015.09.008. Epub 2015 Oct 21.

  PMID: 26654481 BACKGROUND

• Popescu M, Mutalib M. Bowel transit studies in children: evidence base, role and practicalities. Frontline Gastroenterol. 2021 May 10;13(2):152-159. doi: 10.1136/flgastro-2020-101719. eCollection 2022.

  PMID: 35300467 BACKGROUND

• Lambregts AP, Nieuwhof-Leppink AJ, Klijn AJ, Schroeder RPJ. Intravesical botulinum-A toxin in children with refractory non-neurogenic overactive bladder. J Pediatr Urol. 2022 Jun;18(3):351.e1-351.e8. doi: 10.1016/j.jpurol.2022.02.007. Epub 2022 Feb 18.

  PMID: 35283021 BACKGROUND

• Voskuijl WP, Reitsma JB, van Ginkel R, Buller HA, Taminiau JA, Benninga MA. Longitudinal follow-up of children with functional nonretentive fecal incontinence. Clin Gastroenterol Hepatol. 2006 Jan;4(1):67-72. doi: 10.1016/j.cgh.2005.10.001.

  PMID: 16431307 BACKGROUND

• Rajindrajith S, Devanarayana NM, Benninga MA. Review article: faecal incontinence in children: epidemiology, pathophysiology, clinical evaluation and management. Aliment Pharmacol Ther. 2013 Jan;37(1):37-48. doi: 10.1111/apt.12103. Epub 2012 Oct 28.

  PMID: 23106105 BACKGROUND

MeSH Terms

Conditions

Fecal Incontinence

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Central Study Contacts

Dotan Yogev, MD

CONTACT

972 025645027; dotany@szmc.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Dotan Yogev

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: January 21, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: January 24, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share