Oral Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis (UC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health: Programme hospitalier de Recherche Clinique – PHRC-IR 2018

External identifiers

EU CT number

2024-518044-20-00

EudraCT number

2020-000311-71

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 6 months.

Secondary objectives 11

1. 1. Increase in the richness of the recipient's microbiota at 12 months after stool capsules FMT.
2. 2. Increase in the richness of the recipient's microbiota at 6 and 12 months after stool enema FMT.
3. 3. Evaluation of changes in microbiota composition of donor recipient with a composition closer to the healthy donor’s at 6 and 12 months after stool capsules FMT.
4. 4. Evaluation of changes in microbiota composition of donor recipient with a composition closer to the healthy donor’s at 6 and 12 months after stool enema FMT.
5. 5. Evaluation of the change of mucosal microbiota composition after FMT with frozen stool capsules or by enema at 12 months
6. 6. Evaluation of FMT feasibility with frozen stool capsules and by enema in children
7. 7. Evaluation of FMT efficiency with frozen stool capsules and by enema on ulcerative colitis clinical relapse
8. 8. Evaluation of FMT efficiency with frozen stool capsules and by enema on ulcerative colitis endoscopic relapse
9. 9. Evaluation of the effets of FMT with frozen stool capsules and by enema on inflammatory blood markers and faecal biomarkers (faecal calprotectin
10. 10. Evaluation of patient’s quality of life (IMPACT-3 questionnaire) in both arms for patient aged 10 and older between baseline and 12 months
11. 11. Evaluation of the treatment tolerance and security

Conditions and MedDRA coding

Ulcerative Colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient aged 8 to 17 years old
2. Ulcerative colitis (UC), whatever the extent, except isolated proctitis (<5 cm), diagnosed for more than 3 months according to the usual clinical, biological and endoscopic criteria.
3. Moderate active UC defined by a PUCAI score > 35 and responding to corticosteroid treatment with a PUCAI score <10 at enrolment
4. Treatment of UC (5-ASA, immunosuppressants, biotherapies) stable for more than 3 months
5. Patient able to swallow test capsules
6. For girls of childbearing age: To have a negative blood (or urine) pregnancy test To agree to use a reliable contraceptive method from visit 1 until the end of the research
7. Patient with health insurance
8. Informed written consent form signed by both parents or by the person (s) with parental authority

Exclusion criteria 7

1. Isolated proctitis (<5 cm)
2. Being on enteral nutrition
3. Have received antibiotic or antifungal treatment in the 4 weeks prior to enrolment
4. Having a Clostridioides difficile infection in the 4 weeks prior to enrolment;
5. Being pregnant or breastfeeding, or have a positive pregnancy test
6. Participation in other interventional research involving humans
7. Have a contraindication to colonoscopy or general anaesthesia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Success of FMT is defined by an increase in the richness of the recipient's microbiota at 6 months. Microbiota richness will be evaluated by measuring the alpha diversity of the microbiota using Shannon index. The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M6.

Secondary endpoints 11

1. Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 12 months, will be evaluated by the microbiota alpha diversity using the Shannon index. Success is defined by an increase of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M12.
2. Success of FMT by stool enema defined by an increase in the richness of the recipient's microbiota at 12 months will be evaluated by the microbiota alpha diversity using the Shannon index. Success is defined by an increase of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M12.
3. Success of FMT with frozen stool capsules defined by the recipient dysbiotic microbiota being more similar to the healthy donor’s microbiota at 6 and 12 months than the receiver’s before FMT. The success of the FMT is defined by a Bray Curtis (BC) Index [recipient after FMT vs donor] greater than a BC Index [recipient after FMT vs recipient before FMT], with a BC Index [recipient after FMT vs donor] ≥ 0.6
4. Success of FMT by stool enema defined by the recipient dysbiotic microbiota being more similar to the healthy donor’s microbiota at 6 and 12 months than the receiver’s before FMT. The success of the FMT is defined by a Bray Curtis (BC) Index [recipient after FMT vs donor] greater than a BC Index [recipient after FMT vs recipient before FMT], with a BC Index [recipient after FMT vs donor] ≥ 0.6
5. Changes on mucosal microbiota at 0 and 12 months. Mucosal microbiota will be studied on biopsies done during colonoscopies at M0 and M12, the microbiota will be studied using the MISeq (RNA 16S). The same success criteria than faecal microbiota at M0 and M12 will be analysed (using Shannon and Bray Curtis indexes
6. The long term FMT feasibility with frozen stool capsules and by stool enema in children suffering from ulcerative colitis will be evaluated with the number of capsules intake, facility of capsules intake, number of enemas, FMT acceptance, enemas duration, difficulties related to the application of enemas.
7. Ulcerative colitis clinical relapse at 6 and 12 months defined as a Paediatric Ulcerative Colitis Activity Index (PUCAI) > 35, number of relapses during the follow-up, treatments received during the follow-up
8. Ulcerative colitis Endoscopic relapse at 12 months measured using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) during the 12 months colonoscopy. Relapse defined as an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ≥ 2
9. FMT effect on inflammatory blood markers measured by levels of CRP, VS, leucocytes and faecal calprotein at M0, M6, M9 and M12. Faecal calprotectin dosage will be implemented in the Coprologie Fonctionnelle laboratory of Pr Nathalie Kapel in La Pitié Salpêtrière hospital
10. Quality of life evolution in both treatment arms evaluated by the IMPACT-3 questionnaire (35 closed questions, Likert scale from 1 to 5 [global ranking: 35 – 175]). Higher score suggests a better quality of life
11. Adverse events collection : fever, sepsis, infection, inflammatory disease relapse, … etc will be collected for the entire follow up

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Bénédicte Pigneur

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Bénédicte Pigneur

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 20 files

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

Application history

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