Combination of Diet and Oral Budesonide for Ulcerative Colitis

Official title

Remission With Diet for Ulcerative Colitis Exacerbations: A Single Blinded, International Randomized Controlled Clinical and Translational Trial

Overview

The ReDUCE Trial is a multinational single-blinded randomized controlled trial in mild to moderate flare of Ulcerative colitis (UC) disease patients. The purpose of the study is to validate the clinical efficacy of the UCED (Ulcerative colitis Exclusion Diet) with partial enteral nutrition (PEN) using a novel formula. The investigators anticipate that adding a novel specifically designed dietary intervention in addition to drug will lead to superior remission and mucosal healing via changes in the microbiome.

Detailed description

Rational: Ulcerative colitis is currently treated only by medical therapies or surgery and there is no other option to avoid immune suppression.

Thus, developing a dietary therapy that would treat the cause of the disease, while having no side effects, would likely lead to immediate implementation and be sought out by patients hesitant to be on lifelong medications or immune suppression.

Objectives: To evaluate if the UC Exclusion Diet (UCED), can improve outcomes when administered with an oral budesonide regimen to adult patients with mild to moderate UC.

Methods: This will be a 24-week multinational single-blinded randomized controlled trial.

After a baseline flexible sigmoidoscopy, Group 1 will receive oral budesonide 9 mg topical therapy + the UCED+PEN phase 1 diet for 6 weeks, while Group 2 will receive oral budesonide 9 mg topical therapy alone for 6 weeks with no dietary intervention.

Both groups will continue the previous maintenance therapy through week 12 and both groups will stop budesonide at week 6.

Group 1 will continue with the phase 2 diet/PEN from week 7-12 while group 2 will stay on habitual diet. A flexible sigmoidoscopy will be repeated at week 12.

Population: adults and adolescents between the ages of 17-65 with a mild to moderate active disease (Simple Clinical Colitis Activity Index (SCCAI) 5-10 with an endoscopic Mayo score 1-3), on an existing maintenance therapy comparing two arms.

Time frame: The induction of remission phase will last 8 weeks followed by maintenance phase for a period of 24 weeks

Expected outcomes and significance: The investigators anticipate that adding a novel specifically designed dietary intervention in addition to drug will lead to superior remission and mucosal healing via changes in the microbiome.

Interventions

• Other Ulcerative colitis Exclusion Diet
  a limited whole food diet (UCED)
• Other Partial enteral nutrition (PEN)
  The diet will be supplemented by 3 glasses a day (750 m"l) of the formula developed for UC using the UCED principles.
• Other free diet
  oral Budeosnide for 6 weeks + free diet
• Drug Oral Budesonide
  Oral Budesonide 9 mg

Primary outcome measures

• Steroid free remission [Time frame: week 12]

Secondary outcome measures (6)

• Clinical response [Time frame: week 12]
• Steroids free remission [Time frame: week 6]
• Sustained steroid free remission [Time frame: week 24]
• Endoscopic remission [Time frame: week 12]
• Change in medical therapy [Time frame: by week 12]
• Fecal calprotectin [Time frame: week 12]

Eligibility criteria

Inclusion criteria

• Informed consent
• Established diagnosis of UC with mild to moderate active disease, 5 ≤ SCCAI ≤ 10
• Age: 17-65 years (inclusive)
• Extent E1-E3 by the Montreal classification
• Active colitis in the rectum or sigmoid colon on sigmoidoscopy
• Stable medication use of oral 5ASA for at least 8 weeks, thiopurines, vedolizumabs, Ustekinumab or tofacitinib for at least 12 weeks

Exclusion criteria

• Severe colitis (SCCAI>10) hospitalization for acute severe colitis (ASC) in the previous 6 months
• Use of steroids in the previous 3 months
• Patients treated with Anti-TNF currently or in patients who had previously failed or lost response to anti TNF
• Vegans (vegetarians may enroll)
• Pregnancy
• Inability use of budesonide due to severe adverse events
• Extraintestinal manifestations such as arthritis, spondyloarthropathy or uveitis
• Presence of baseline hypoalbuminemia
• Fever >38°C
• Evidence for Clostridioides difficile infection
• Renal failure
• Hepatitis or PSC (Primary Sclerosing Cholangitis)
• Active malignancy (excluding skin BCC).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Israel · 3 centers

• Emek Medical Center — Afula
• Wolfson Medical Center — Holon
• Tel Aviv Sourasky Medical Center — Tel Aviv

Italy · 1 center

• FONDAZIONE GEMELLI HOSPITAL Catholic University of the Sacred Hearth — Roma

Netherlands · 1 center

• Radboud University Medical Center (Radboudumc) — Nijmegen

Switzerland · 1 center

• Kantonsspital St. Gallen — Sankt Gallen

Publications

• 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 Colit PMID 34514495
• Sarbagili-Shabat C, Albenberg L, Van Limbergen J, Pressman N, Otley A, Yaakov M, Wine E, Weiner D, Levine A. A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study. Nutrients. 2021 Oct 23;13(11):3736. doi: 10.3390/nu13113736. PMID 34835992

Identifiers

NCT: NCT05791487 · 0073-22-WOMC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗