Clinical trial NCT05791487: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Ulcerative Colitis Chronic Mild
Ulcerative Colitis Chronic Moderate
Keywords: Ulcerative colitis
Diet
Partial enteral nutrition
Microbiome
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2023-03-30
Enrollment: 90
Sex: ALL
Minimum age (years): 17
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Primary outcomes:
measure: Steroid free remission
timeFrame: week 12
Secondary outcomes:
measure: Clinical response
timeFrame: week 12
measure: Steroids free remission
timeFrame: week 6
measure: Sustained steroid free remission
timeFrame: week 24
measure: Endoscopic remission
timeFrame: week 12
measure: Change in medical therapy
timeFrame: by week 12
measure: Fecal calprotectin
timeFrame: week 12
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Emek Medical Center
city: H̱olon
country: Israel
facility: Wolfson Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Roma
country: Italy
facility: FONDAZIONE GEMELLI HOSPITAL Catholic University of the Sacred Hearth
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center (Radboudumc)
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
References:
citation: 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.
citation: 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.