Fecal Transplantation Using a Diet for Donor and Recipient in Refractory Colitis

NCT02734589 | Terminated

• 1 other identifier: 0070-15
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 5

Brief Summary

Changing the microbiota has become the most intriguing target for intervention in inflammatory bowel disease (IBD). Dietary therapy is successful in mild to moderate Crohn's disease and may be effective in mild to moderate ulcerative colitis (UC) as well, though dietary interventions in UC are just getting underway. However these interventions are less likely to be effective for the more severely inflamed or refractory end of the spectrum. Fecal transplantation (FT) has been suggested as a method to treat refractory IBD, but most studies have been unsuccessful in establishing remission and especially sustained remission. The investigators hypothesize that this is due to selection of random donors and the inability to maintain an optimal microbiota eco system post transplant. Diet is a powerful tool to modulate the microbiota. The investigators propose that use of a donor and recipient diet designed for UC during fecal transplantation will be superior to diet alone of fecal transplantation alone and will improve patient outcomes.The investigators propose to modify FT using a novel protocol and approach that we have developed. We have developed a unique diet that is geared to rectify dysbiosis in UC and damage to the mucous layer in active UC. The investigators intend to condition both donor and recipient with the diet to achieve optimal conditions for transplant to succeed for both donor and recipient .The investigators intend to evaluate this protocol in adults with active UC that are refractory to medications. The investigators will start with a randomized controlled trial involving 76 transplanted patients+ 20 subjects for dietary controls with the UC diet alone.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Nutrition; microbiome

Outcome Measures

Primary Outcomes (1)

• Clinical remission

  determined by Simple Clinical Colitis Activity Index (SCCAI) score \<3 at week 8

  Day 56

Secondary Outcomes (6)

• Improvement

  Days 56 & 84

• Endoscopic resutls

  Day 56

• Calprotectin

  Day 56

• The need for additional therapy or flare

  Week 12

• change in the microbiome compared to baseline.

  For donor- day 14 and for recipient day 56

Study Arms (3)

Fecal microbiota transplantation (FMT) without Diet

ACTIVE COMPARATOR

undergo standard fecal transplantation by colonoscopy on day 1 and 60 ml rectal enemas on days 2 and 14 from the same donor without dietary conditioning.

Other: Fecal transplantation

FMT with Diet for the donor and for the recipient

EXPERIMENTAL

undergo standard fecal transplantation by colonoscopy on day 1 and 60 ml rectal enemas on days 2 and 14 with dietary pre-conditioning of the donor for 14 days and dietary treatment of the recipient immediately after transplantation and for the following 12 weeks.

Other: Unique novel Diet for UC and Unique novel Diet for the donor + FMT

Dietary therapy only

ACTIVE COMPARATOR

The patient will receive detailed instructions regarding the UC diet to be used over 12 weeks without FMT.

Other: Unique novel Diet for UC

Interventions

Fecal transplantation OTHER

Transplantation of fecal bacteria from a healthy individual into a recipient- ulcerative colitis patient via colonoscopy and enemas

Also known as: Fecal microbiota transplantation (FMT)

Fecal microbiota transplantation (FMT) without Diet

Unique novel Diet for UC and Unique novel Diet for the donor + FMT OTHER

A developed unique diet that is geared to induces remission and decreases inflammation in patients with active UC. Also a conditioning diet for healthy subjects to be used by the donor prior to transplantation- a developed unique diet for two weeks.

Also known as: Ulcerative Colitis Diet (UCD) and the conditioning diet

FMT with Diet for the donor and for the recipient

Unique novel Diet for UC OTHER

A developed diet that is geared to induces remission and decreases inflammation in patients with active UC.

Also known as: Ulcerative Colitis Diet (UCD)

Dietary therapy only

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Established diagnosis of UC, disease confined to the large intestine, involving the rectosigmoid for at least 3 months.
• Age: 18 - 70 years ( inclusive)
• Mild to Moderate active disease, SCCAI of ≥5 and \<10 with endoscopic subscore≥2
• Refractory to mesalamine 6 weeks, or steroids \> 14 days, or immunomodulator 12 weeks or biologics at least 12 weeks therapy.
• No use or stable use for 2 weeks of medical cannabis.
• \. Patients can enter the trial if they are on steroids if they have been treated for at least two weeks with 40 mg prednisone or an intravenous steroid such as methylprednisolone and still suffer from a mild to moderate active disease.

You may not qualify if:

• Start of a new biologic in the previous 12 weeks.
• Evidence for Clostridium difficile infection.
• Any proven current infection such as CMV, positive stool culture or parasite.
• Current Extra intestinal manifestation of UC such as active arthritis or primary sclerosing cholangitis (PSC).
• Immune deficiency (other than drug induced).
• Current use of a calcineurin inhibitor
• Pregnancy.
• Suspected toxic megacolon, guarding on palpation, or signs of peritoneal inflammation
• Patients with other IBD unrelated disease such as autoimmune disorders, renal failure, fever or current infection (UTI, strep throat, pneumonia, etc), prior or current neoplasia
• Fecal Transplantation in the last 6 months.
• Fever \>38
• Participation in another clinical interventional trial
• An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
• Inability or reluctance to use an enema.
• Anticipation for antibiotic use within the study period (such as for elective surgery or dental treatment).

Sponsors & Collaborators

• Wolfson Medical Center: lead

Study Sites (5)

Saint-Antoine Hospital, Universite Pierre et Marie Curie

Paris, 75571, France

Location

Wolfson Medical Center

Holon, 58100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Humanitas Clinical and Research Center

Milan, Italy

Location

Catholic University of the Secret Heart

Rome, Italy

Location

Related Publications (1)

• Sarbagili Shabat C, Scaldaferri F, Zittan E, Hirsch A, Mentella MC, Musca T, Cohen NA, Ron Y, Fliss Isakov N, Pfeffer J, Yaakov M, Fanali C, Turchini L, Masucci L, Quaranta G, Kolonimos N, Godneva A, Weinberger A, Kopylov U, Levine A, Maharshak N. Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial. J Crohns Colitis. 2022 Mar 14;16(3):369-378. doi: 10.1093/ecco-jcc/jjab165.

  PMID: 34514495 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Arie Levine, MD

  Wolfson Medical Center

  PRINCIPAL INVESTIGATOR

• Yona Avni, MD

  Wolfson Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: single blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pediatric Gastroenterology and Nutrition unit.

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: April 12, 2016
• Study Start: January 24, 2017
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: June 1, 2022

Record last verified: 2022-05

Locations

IT (2); IL (2); FR (1)