Clinical trial NCT05579483: Prediction of Dietary Intervention Efficacy in Mild Ulcerative Colitis Patients Based on Fecal Microbiome Signatures
Official title: Prediction of Dietary Intervention Efficacy in Mild Ulcerative Colitis Patients Based on Fecal Microbiome Signatures
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Keywords: prebiotics
ulcerative colitis
gut microbiome signature
fiber intake
prediction
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: Winclove Probiotics B.V.
name: China Scholarship Council
First posted: 2022-10-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, placebo-controlled, parallel, double-blind trial with two intervention arms and two control (placebo) arms.
Primary purpose: TREATMENT

Brief summary: A double-blind randomized placebo-controlled parallel trial with two intervention arms and two placebo arms and a period of eight intervention weeks to validate the prediction that prebiotics could induce a higher response in mild UC patients with certain fecal microbiome signatures.

Detailed description: Rationale: Ulcerative colitis (UC) patients respond differently to treatments/interventions (e.g. diet/fecal microbiota transplantation), but the reason for this individual specificity remains unknown. The investigators hypothesize that the baseline fecal microbiota composition determines the efficacy of a treatment/intervention, and potential responders, i.e. patients showing symptoms improvement after treatment, can be predicted based on fecal microbiota composition.

Objective: The primary objective is to validate the prediction that prebiotics intervention boosts butyrate production and thereby induces a higher response (lower mean Patient Simple Clinical Colitis Activity Index (P-SCCAI) score) in mild UC patients with low intestinal Bacteroidetes levels (predicted responders), but not in those with high intestinal Bacteroidetes levels (predicted non-responders) at T = 8 weeks. The secondary objectives are to study the effects of prebiotics intervention on disease activity over time (T = 0, 4, 8, 12 and 60 weeks), mucosal inflammation, gastro-intestinal (GI) complaints, stool consistency, stool frequency, fecal microbiota composition, fecal short-chain fatty acids concentrations, quality of life, number of participants with increased or decreased medication use, and incidence of adverse events in mild UC patients.

Study design: This study is a four-arm double-blind randomized placebo-controlled parallel trial. It consists of a screening stage in which mild UC patients will be assigned to be predicted responders or predicted non-responders based on fecal Bacteroidetes levels. Afterwards the predicted responders and non-responders will be assigned to either the prebiotics group (arm 1 and 3) or placebo group (arm 2 and 4).

Study population: Adult subjects aged 18-65 years and body mass index 18-30 kg/m2 with mild UC defined by P-SCCAI (3-5 points in a 19-point scale), with at least one relapse in the last two years.

Intervention: An 8-week intervention period with four parallel arms: 1) predicted responders with prebiotics treatment (acacia gum, partially hydrolyzed guar gum, and resistant starch), 2) predicted responders with placebo (maltodextrin and corn starch), 3) predicted non-responders with prebiotics treatment, 4) predicted non-responders with placebo, during which the study participants consume the respective supplement (3 grams, twice daily).

Main study parameters/endpoints: The main parameter is the response (mean P-SCCAI score) between arms at T = 8 weeks. The secondary parameters are the disease activity over time at T = 0, 4, 8, 12, and 60 weeks, mucosal inflammation (fecal calprotectin), gastro-intestinal (GI) complaints, stool consistency, stool frequency, fecal microbiota composition, fecal short-chain fatty acids concentrations, health-related quality of life, number of participants with increased or decreased medication use, and incidence of adverse events.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects aged 18 to 65 years
2. Body Mass Index (BMI) between 18 and 30 kg/m2 (self-reported)
3. Ulcerative Colitis confirmed via previous endoscopy and histology
4. Mild active UC as defined by P-SCCAI score of 3 to 5 (range 0 to 19)
5. Frequent relapse (at least one exacerbation in the last two years)
6. No known allergy to any components of the study product (self-reported)
7. Signed informed consent
8. Stable UC medication defined as no switch to other medication or no dose change
9. Mobile phone on which apps (used for questionnaires) can be downloaded (iOS version 9 and newer, Android version 4.4 and newer. Phones manufactured after 2013 are usually suitable)
10. Stable dietary pattern during the study

Exclusion Criteria:

1. Any other underlying disease of the GI-tract or previous bowel surgery, except cholecystectomy and appendectomy
2. Pregnancy or intending to become pregnant during the study
3. Use of medication that can interfere with the study outcomes, as judged by the medical supervisor
4. The need for antibiotic use during the intervention period
5. Systemic antibiotics and proton pump inhibitors (except for omeprazole and pantoprazole with dosage \<20 mg), prebiotic supplements, probiotic supplements four weeks prior to study start
6. Currently participating in another intervention study
7. Acquaintances of anyone in the research team

Primary outcomes:
measure: Response between arms at T = 8 weeks
timeFrame: Response at the end the intervention (T= 8 weeks)
Secondary outcomes:
measure: Disease activity over time (T= 0, 4, 8, 12, and 60 weeks)
timeFrame: Disease activity during and after the intervention (at T= 0, 4, 8, 12, and 60 weeks)
measure: Mucosal inflammation
timeFrame: Change during and after the intervention (at T= 0, 8, 12, and 60 weeks)
measure: GI complaints
timeFrame: Change during the intervention (at T= 0, 4, and 8 weeks)
measure: Stool consistency
timeFrame: Change during the intervention (at T= 0, 4, and 8 weeks)
measure: Stool frequency
timeFrame: Change during the intervention (at T= 0, 4, and 8 weeks)]
measure: Fecal microbiota composition
timeFrame: Change during and after the intervention (at T= 0, 8, 12, and 60 weeks)
measure: Fecal short-chain fatty acids concentrations
timeFrame: Change during and after the intervention (at T= 0, 8, 12, and 60 weeks)
measure: Health-related quality of life
timeFrame: Change during the intervention (at T= 0, 4, and 8 weeks)
measure: Number of participants with increased or decreased medication use
timeFrame: Change during and after the intervention (at T= 0, 4, 8, 12, and 60 weeks)
measure: Incidence of adverse events
timeFrame: Change during the intervention (at T= 0, 4, and 8 weeks)
Other outcomes:
measure: Habitual dietary intake
timeFrame: FFQ will be taken at T= 0 (baseline).
measure: Participants demographics and characteristics
timeFrame: This information will be collected at T= 0 (baseline).
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University
state: Gelderland
Study officials:
affiliation: Laboratory of Microbiology, Wageningen University
name: Erwin G Zoetendal, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu Z, de Vries B, Gerritsen J, Smidt H, Zoetendal EG. Microbiome-based stratification to guide dietary interventions to improve human health. Nutr Res. 2020 Oct;82:1-10. doi: 10.1016/j.nutres.2020.07.004. Epub 2020 Jul 21.
citation: Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut. 2021 Mar;70(3):595-605. doi: 10.1136/gutjnl-2020-321747. Epub 2020 Oct 13.