Clinical trial NCT03582969: Capsulized Fecal Microbiota Transplantation in Pediatric Ulcerative Colitis Patients
Official title: High Intensity, Multi-Donor, Oral Capsulized Fecal Microbiota Transplantation in Newly Diagnosed Pediatric Patients With Mild to Moderate Ulcerative Colitis - a Double Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: IBD
UC
fecal-transplantation
capsules
microbiota
microbiome
colitis
pediatric
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2018-07-11
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a placebo-controlled, double blinded interventional study evaluating oral, fecal microbiota transplantation, administered in patients with mild-moderate UC.
Primary purpose: TREATMENT

Brief summary: Fecal Microbiota Transplantation(FMT) - reconstitution of normal flora by a stool transplant from a healthy individual, is increasingly being recognized as a therapeutic modality for diseases that are associated with gut dysbiosis.

This is a placebo-controlled, double blinded interventional study evaluating multiple, oral, fecal microbiota transplantation, administered in newly diagnosed pediatric patients with mild-moderate UC.

The primary objective is to assess the safety and feasibility of multiple, oral, fecal microbiota transplantation, in newly diagnosed pediatric patients with mild-moderate UC.

All processing will occur at the Center for Microbiome Research at Assaf Harofeh Medical Center, under GMP conditions.


Eligibility criteria: Inclusion Criteria:

* Patients newly diagnosed (\>9 months) with mild to moderate ulcerative colitis as per colonic biopsy and clinical disease activity (SCCAI 5-12).
* Patients not started on immune-suppressive or anti-inflammatory medications (Mesalamine is allowed).
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of childbearing potential will have a urine pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after FMT.
* Ability to understand and the willingness to sign a written document, including the willingness to accept risk of unrelated donor stool.
* Ability of parents or other legal guardian to understand and the willingness to sign a written informed consent document, including the willingness to accept risk of unrelated donor stool.
* Ability to swallow oral medications.

Exclusion Criteria:

* Severe, uncontrolled ulcerative colitis.
* At time of enrollment, immune-suppressive or anti-inflammatory medications, except Mesalamine.
* Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
* Delayed gastric emptying syndrome
* Known chronic aspiration
* Patients with a history of significant allergy to foods not excluded from the donor diet (excluded foods are tree nuts, peanuts, shellfish, eggs)
* Pregnant and breast-feeding women
* Participants who are unable to swallow pills.

Primary outcomes:
measure: UC remission
timeFrame: 12 weeks
Secondary outcomes:
measure: Improvement in UC symptoms
timeFrame: 12 weeks
measure: markers of inflammation
timeFrame: 12 weeks, 6 months and 12 months
measure: Improvement in UC endoscopic score
timeFrame: 12 weeks, 6 months and 12 months
measure: change in gut microbiome
timeFrame: 12 weeks, 6 and 12 months.
measure: use of treatments for UC
timeFrame: 6+12 months
measure: Extra-intestinal disease manifestations
timeFrame: 6 and 12 month
Other outcomes:
Locations:
city: Zerifin
country: Israel
facility: Assaf-HarofehMC
Study officials:
References:
citation: Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 May 5;162(9):630-8. doi: 10.7326/M14-2693.
citation: Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojarvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science. 2016 Apr 29;352(6285):586-9. doi: 10.1126/science.aad8852.
citation: Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol. 2015 May 7;21(17):5359-71. doi: 10.3748/wjg.v21.i17.5359.
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citation: Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt T. Fecal Microbiota Transplantation for Clostridium Difficile Infection: A Systematic Review of the Evidence [Internet]. Washington (DC): Department of Veterans Affairs (US); 2014 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK299000/
citation: Scaldaferri F, Pecere S, Petito V, Zambrano D, Fiore L, Lopetuso LR, Schiavoni E, Bruno G, Gerardi V, Laterza L, Pizzoferrato M, Ianiro G, Stojanovic J, Poscia A, Papa A, Paroni Sterbini F, Sanguinetti M, Masucci L, Cammarota G, Gasbarrini A. Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis. Transplant Proc. 2016 Mar;48(2):402-7. doi: 10.1016/j.transproceed.2015.12.040.
citation: Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.
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citation: Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.
citation: 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.