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Crohn DiseasePhase 3MIRACLENCT04997733

Fecal Microbiota Transplantation in Crohn's Disease as Relay After Anti-TNF Withdrawal

A Phase 3 study testing Fecal Microbiota Transplantation (FMT) in people with Crohn Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Crohn's disease (CD) is a chronic inflammatory bowel disease. CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts. Read more about this study

Who is it for?
Ages 18 to 74 yearsHealthy volunteers can take part
Conditions the study is for
Crohn Disease
What is being tested?
Fecal Microbiota Transplantation (FMT)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
1 siteFrance
Study dates
22 Sep 2021to 22 Jul 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 74 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years and < 75 years
  • Crohn's disease (according to the Lennard-Jones criteria) for at least 6 months
  • Patient in steroid-free clinical remission for at least 6 months under anti-TNF agent (no clinical evidence of flare nor change in Crohn's disease specific treatment (anti-TNF, immunosuppressive, …) within 6 months before inclusion) and CDAI <150 the week before inclusion) and willing to withdraw anti-TNF treatment
  • Female of child-bearing age with an active contraception and this during at least the period of treatment (week 52)
  • Patient with health insurance
  • Informed Written consent
Show all 11Show fewer
  • Age ≥ 18 years and < 50 years
  • 17 kg/m² < body mass index < 30 kg/m²
  • Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day
  • Subject with health insurance (AME excepted)
  • Informed written consent

Who cannot join

  • Crohn's Disease complication requiring surgical treatment
  • Contraindication to colonoscopy or anesthesia
  • Pregnancy or breastfeeding during the study (Cf. Addendum 4)
  • Diagnosis of Crohn's disease restricted to the upper gastrointestinal tract (oesophagus, stomach, duodenum, jejunum)
  • Patient with active perineal disease (defined as evidence of perineal abscess or active draining fistula or presence of seton or presence of perineal ulceration)
  • History of more than one small bowel resection or small intestine resection > 1 meter
Show all 10Show fewer
  • Current stoma (Ileostomy or a colostomy) or stoma in the last 6 months or any other intra-abdominal surgery within 3 months prior to inclusion
  • Participation in any other interventional study
  • Patient under legal protection
  • For details, please see protocol

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Harry SOKOL, PU-PH contact

01 49 28 31 62

harry.sokol@aphp.fr

France1 site, 1 recruiting
  • Gastroenterology Department of Saint Antoine Hospital

    Paris, 75012

    Harry SOKOL, PU-PH, 01 49 28 31 62 ext. +33, harry.sokol@aphp.fr

    Laurent BEAUGERIE, PU-PH, 01 49 28 31 62, laurent.beaugerie@aphp.fr

    Recruiting

Other trials in France

About this study

Crohn's disease (CD) is a chronic inflammatory bowel disease. CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts.

The purpose of this study is to evaluate de clinical efficacy of the fecal microbiota transplantation (FMT) as a maintenance treatment following anti-TNF agent withdrawal in CD's patient.

Read the detailed description

Crohn's disease (CD) is a chronic inflammatory bowel disease affecting approximately 120000 patients in France, mostly at young age, and altering their quality of life.

Immunosuppressive treatments in CD are expensive and associated with potentially severe complications.

Alternative treatment strategies are thus required. This is particularly the case for CD patients in remission under anti-TNF agents for which no specific recommendation are available.

CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota in predisposed hosts.

Fecal microbiota transplantation (FMT) is currently recommended for treating recurrent Clostridium difficile infection. Although the pathogenesis involved in CD differs, FMT is a potential therapeutic strategy that could restore the appropriate host-microbiota crosstalk by transferring a healthy microbiota in a CD patient. However, as the gut microbiota is dramatically altered by intestinal inflammation, transferring a massive amount of microbes in an inflamed gut with epithelial barrier disruption might be a suboptimal strategy and could even have detrimental effects by allowing bacterial translocation.

Results of randomized controlled trial (RCT) in CD are lacking to date. We performed a pilot RCT (NCT02097797), evaluating the impact of a single FMT in 18 CD patients who achieved remission by corticosteroid treatment. A higher rate of steroid free clinical remission was observed in the FMT arm at 24 weeks (57.1% vs 33.3% in FMT and control arm respectively). CD Endoscopic Index of Severity was also improved at 6 weeks in FMT (median 8.5 vs 3.5 p=0.03) but not in sham group (median 2.4 vs 2.7 p=0.8). Moreover, the only 2 patients who early relapsed in the FMT group were those who did not show any engraftment of donor microbiota at week 6. These promising data, currently submitted for publication, suggest that using FMT as a maintenance treatment in CD can be effective. However, these promising findings need to be confirmed by a Phase III RCT.

Conditions
Crohn Disease
Being tested
Fecal Microbiota Transplantation (FMT), Sham-transplantation (placebo)
Keywords
Crohn disease, Inflammatory bowel disease, Fecal microbiota transplantation
Medical subject headings
Crohn Disease, Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fecal Microbiota Transplantation (FMT)Drug

    The colonoscopy for FMT will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either FMT (frozen preparation of 50g of stools in 300ml of saline (NaCl 0.9%), (FMT vehicle in the terminal ileum or the colon.

    At W12 and W24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain 0.8g of stools by visit).

  • Sham-transplantation (placebo)Drug

    The colonoscopy for sham-transplantation will be planned between 7 and 14 days after the last adalimumab or sub-cutaneous infliximab administration and 6 weeks +/- 7 days after the last intravenous infliximab administration, 14 and 28 days following the last sub-cutaneous golimumab administration. After colon cleansing using polyethylene glycol, the patient will have a colonoscopy under general anesthesia. The patient will then receive either sham transplantation (frozen preparation of NaCl 0.9% with 10% glycerol) in the terminal ileum or the colon.

    At S12 and S24 after first colonoscopy, the patient receives treatment by capsule (15 capsules contain placebo).

Study groups in NCT04997733
Study groupRoleWhat they receive
Fecal microbiotaExperimentalPatients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation (endoscopic and oral)
Receives: Drug: Fecal Microbiota Transplantation (FMT)
Sham-transplantationSham comparatorPatients receiving the sham-transplantation in 3 times after inclusion and randomisation (endoscopic and oral)
Receives: Drug: Sham-transplantation (placebo)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the clinical efficacy of FMT versus sham transplantation as a maintenance treatment following anti-TNF agent withdrawal in patients with Crohn's disease in steroid-free clinical remission for at least 6 months under anti-TNF agent

    Clinical remission (defined by a Crohn's disease activity index (CDAI) <150) at week 52 (V8) without any flare between week 0 (colonoscopy (V2)) and week 52 (V8). Flare is defined by a CDAI (Addendum 2) above 250 or between 150 points and 250 points with a 70-point increase from baseline over 2 consecutive weeks and the need

    Measured: 52 weeks after FMT or sham-transplantation

Secondary outcomes (1)
  1. Relapse free survival

    Relapse free survival rate from week 0 (V2) to week 52 (V8)

    Measured: 52 weeks after FMT or sham-transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2021
  2. Study start22 Sep 2021
  3. Primary completion22 May 2027 (estimated)
  4. Study completion22 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04997733
Sponsor's protocol ID
APHP190183
Other IDs
2019-003816-29, 2019
Acronym
MIRACLE
Status last verified
Aug 2025
First submitted
5 Jul 2021
Last updated
11 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015 Apr;12(4):205-17. doi: 10.1038/nrgastro.2015.34. Epub 2015 Mar 3.

    PubMed 25732745
  • Angelberger S, Reinisch W, Makristathis A, Lichtenberger C, Dejaco C, Papay P, Novacek G, Trauner M, Loy A, Berry D. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol. 2013 Oct;108(10):1620-30. doi: 10.1038/ajg.2013.257. Epub 2013 Sep 24.

    PubMed 24060759
  • Beaugerie L, Itzkowitz SH. Cancers Complicating Inflammatory Bowel Disease. N Engl J Med. 2015 Jul 9;373(2):195. doi: 10.1056/NEJMc1505689. No abstract available.

    PubMed 26154801
  • Ben-Horin S, Chowers Y. Review article: loss of response to anti-TNF treatments in Crohn's disease. Aliment Pharmacol Ther. 2011 May;33(9):987-95. doi: 10.1111/j.1365-2036.2011.04612.x. Epub 2011 Mar 2.

    PubMed 21366636
  • Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976 Mar;70(3):439-44.

    PubMed 1248701
  • Borody T, Fischer M, Mitchell S, Campbell J. Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead. Expert Rev Gastroenterol Hepatol. 2015;9(11):1379-91. doi: 10.1586/17474124.2015.1086267. Epub 2015 Sep 28.

    PubMed 26414076
  • Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2014 Dec;8(12):1569-81. doi: 10.1016/j.crohns.2014.08.006. Epub 2014 Sep 13.

    PubMed 25223604
  • Cui B, Li P, Xu L, Zhao Y, Wang H, Peng Z, Xu H, Xiang J, He Z, Zhang T, Nie Y, Wu K, Fan D, Ji G, Zhang F. Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med. 2015 Sep 12;13:298. doi: 10.1186/s12967-015-0646-2.

    PubMed 26363929
  • Cui B, Feng Q, Wang H, Wang M, Peng Z, Li P, Huang G, Liu Z, Wu P, Fan Z, Ji G, Wang X, Wu K, Fan D, Zhang F. Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol. 2015 Jan;30(1):51-8. doi: 10.1111/jgh.12727.

    PubMed 25168749
  • D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lemann M, Marteau P, Rutgeerts P, Scholmerich J, Sutherland LR. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007 Feb;132(2):763-86. doi: 10.1053/j.gastro.2006.12.038. Epub 2006 Dec 20. No abstract available.

    PubMed 17258735
  • Debast SB, Bauer MP, Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014 Mar;20 Suppl 2:1-26. doi: 10.1111/1469-0691.12418.

    PubMed 24118601
  • Grinspan AM, Kelly CR. Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet. Gastroenterology. 2015 Jul;149(1):15-8. doi: 10.1053/j.gastro.2015.05.030. Epub 2015 May 27. No abstract available.

    PubMed 26021232
  • Kennedy NA, Warner B, Johnston EL, Flanders L, Hendy P, Ding NS, Harris R, Fadra AS, Basquill C, Lamb CA, Cameron FL, Murray CD, Parkes M, Gooding I, Ahmad T, Gaya DR, Mann S, Lindsay JO, Gordon J, Satsangi J, Hart A, McCartney S, Irving P; UK Anti-TNF withdrawal study group; Lees CW. Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis. Aliment Pharmacol Ther. 2016 Apr;43(8):910-923. doi: 10.1111/apt.13547. Epub 2016 Feb 19.

    PubMed 26892328
  • Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, Gordon S, Gluck M, Hohmann EL, Kao D, Kao JY, McQuillen DP, Mellow M, Rank KM, Rao K, Ray A, Schwartz MA, Singh N, Stollman N, Suskind DL, Vindigni SM, Youngster I, Brandt L. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065-71. doi: 10.1038/ajg.2014.133. Epub 2014 Jun 3.

    PubMed 24890442
  • Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015 Jul;149(1):223-37. doi: 10.1053/j.gastro.2015.05.008. Epub 2015 May 15.

    PubMed 25982290

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fecal Microbiota Transplantation (FMT) in people with Crohn Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Harry SOKOL, PU-PH (01 49 28 31 62, harry.sokol@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the clinical efficacy of FMT versus sham transplantation as a maintenance treatment following anti-TNF agent withdrawal in patients with Crohn's disease in steroid-free clinical remission for at least 6 months under anti-TNF agent (time frame: 52 weeks after FMT or sham-transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04997733, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.

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