Combination of Diet and Oral Budesonide for Ulcerative Colitis

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Ulcerative colitis Exclusion Diet
  a limited whole food diet (UCED)
• Другое 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.
• Другое free diet
  oral Budeosnide for 6 weeks + free diet
• Препарат Oral Budesonide
  Oral Budesonide 9 mg

Первичные конечные точки

• Steroid free remission [Срок оценки: week 12]

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Израиль · 3 центра

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

Италия · 1 центр

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

Нидерланды · 1 центр

• Radboud University Medical Center (Radboudumc) — Nijmegen

Швейцария · 1 центр

• Kantonsspital St. Gallen — Sankt Gallen

Публикации

• 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

Идентификаторы

NCT: NCT05791487 · 0073-22-WOMC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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