Prediction of Dietary Intervention Efficacy in Mild Ulcerative Colitis Patients Based on Fecal Microbiome Signatures (PREDUCTOME)

Wageningen University

Status: Not yet enrolling

Conditions: Ulcerative Colitis

Treatments: Dietary Supplement: Placebo; Dietary Supplement: Prebiotics

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05579483

NL79442.091.22 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 4 patient groups, including a placebo group

Predicted responders with prebiotics

Experimental group

Description:

Predicted responders, which are defined as UC patients having a relative abundance of Bacteroidetes \<=10% in their feces, will receive 6 grams of prebiotics per day.

Treatment:

Dietary Supplement: Prebiotics

Predicted responders with placebo

Placebo Comparator group

Description:

Predicted responders, which are defined as UC patients having a relative abundance of Bacteroidetes \<=10% in their feces, will receive 6 grams of placebo per day.

Treatment:

Dietary Supplement: Placebo

Predicted non-responders with prebiotics

Experimental group

Description:

Predicted non-responders, which are defined as UC patients having a relative abundance of Bacteroidetes \>=15% in their feces, will receive 6 grams of prebiotics per day.

Treatment:

Dietary Supplement: Prebiotics

Predicted non-responders with placebo

Placebo Comparator group

Description:

Predicted non-responders, which are defined as UC patients having a relative abundance of Bacteroidetes \>=15% in their feces, will receive 6 grams of placebo per day.

Treatment:

Dietary Supplement: Placebo