Clinical trial NCT05230160: Can Intermittent Fasting Induce Weight Loss and Improve Gut Health as Compared to Standard Medical Care in Patients With Obesity/High BMI and Crohn's Disease.
Official title: Can Intermittent Fasting Induce Weight Loss and Improve Gut Health as Compared to Standard Medical Care in Patients With Obesity/High BMI and Crohn's Disease.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Crohn Disease
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2022-02-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Diet is a determinant of gut microbial diversity and composition and is recognized as a potential environmental trigger for IBD; for example, high-fat diets are associated with increased risk of CD in pre-clinical models, with effects mediated through dysbiosis and altered gut permeability.

Diet is also a potential non-pharmacological therapy for weight loss and for reducing the occurrence of disease flares and the reliance on dose escalation of biologic agents. Indeed, there is accumulating evidence for the role of diet in the treatment of CD, and diet-induced improvement of microbial dysbiosis is associated with induction of remission in pediatric patients with active CD.

Intermittent Fasting (IF) is a dietary intervention that involves periodic intervals of no or very limited energy intake. We want to determine the efficacy and feasibility of a 12-week IF(Intermittent Fasting) intervention to induce weight loss (by 1 BMI unit reduction), decrease biomarker inflammation and increase microbial functional diversity compared to standard medical management (SM) in a pilot study of individuals with overweight or obesity and CD in clinical remission with elevated biomarkers of inflammation, indicated by fecal calprotectin (FCP) \> 250 µg/g or C-reactive protein (CRP) \> 5 mg/L).

Detailed description: Objectives: To determine if a 12-week IF intervention compared to SM:

1. Induces weight loss of at least 1 BMI unit.
2. Reduces intestinal and systemic inflammation.
3. Alters gut microbial community structure (beta-diversity) from baseline.
4. Alters the adipokines and myokines leptin, adiponectin, IL-6, or irisin.
5. Alters zonulin and serum levels of gastrointestinal hormones ghrehlin, glucagon-like peptide 1 (GLP-1), and glucagon-like peptide 2 (GLP-2).
6. Alters body composition and whether changes in body composition have an effect on biomarkers of inflammation.
7. Is a feasible and sustainable intervention for patients with CD.

Hypotheses: We hypothesize that, compared to SM, IF will:

1. Induce at least a 1-unit decrease in BMI over the course of the intervention.
2. Improve inflammatory markers of CD, demonstrated by a decrease in FCP by ≥ 50%, normalization of FCP to ≤ 100 µg/g, or a decrease in CRP to ≤ 5 mg/L.
3. Alter gut microbial community structure (beta-diversity ) and lead to enrichment of bacterial species typically depleted in CD, such as Faecalibacterium prausnitzii and Roseburia hominus with concomitant decreases in Escherichia coli and overall Proteobacteria phylum abundance.
4. Alter adipokines and myokines (leptin, adiponectin, IL-6, and irisin), zonulin and serum levels of gastrointestinal hormones (ghrehlin, GLP-1, and GLP-2).
5. Alter body composition by decreasing VAT.
6. Be a feasible and sustainable treatment option for patients with CD

Methods

Study Design:

The study is a 12-week pilot randomized controlled trial (RCT). Eligible participants (N=42) will be randomized 1:1 to either the IF or the SM control group. Patients from the University of Calgary IBD clinic will be enrolled in the RCT.

Screening:

The study RD will assess participants for malnutrition using the abridged patient-generated subjective global assessment (PG-SGA), a validated tool to determine malnutrition status in patients with chronic disease. The Nine Item Avoidant/Restrictive Food Intake Disorder screen33 will be completed to rule out avoidant and restrictive food behaviours that may increase the malnutrition risk of an IF intervention.

Inclusion criteria:

1) ≥ 18 to ≤ 75 years of age; 2) ileocolonic or colonic CD in clinical remission diagnosed through conventional definitions with a Harvey Bradshaw Index (HBI) \< 5 within 3 months of recruitment; 3) presence of inflammation using an FCP ≥ 250 µg/g or a CRP ≥ 5 mg/L; 4) stable dosing of biologic agents and/or immunomodulators and/or oral or rectal 5-ASA, and no changes to medical management (including corticosteroid exposure) for at least 3 months prior to recruitment; and 5) presence of overweight or obesity with BMI \> 25 and a PG-SGA of class A.

Exclusion criteria:

1) upper gastrointestinal involvement CD, fistulizing disease; 2) documented strictures based on sonographic findings or colonoscopy within the last year; 3) \> 1 small bowel resection; 4) colectomy; 5) presence of an ostomy; 6) antibiotic use in past 3-months; 7) pregnancy; and 8) corticosteroids in the last 3 months.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 to ≤ 75 years of age;
2. ileocolonic or colonic CD in clinical remission diagnosed through conventional definitions with a Harvey Bradshaw Index (HBI) \< 5 within 3 months of recruitment;
3. presence of inflammation using an FCP ≥ 250 µg/g or a CRP ≥ 5 mg/L;
4. stable dosing of biologic agents and/or immunomodulators and/or oral or rectal 5-ASA, and no changes to medical management (including corticosteroid exposure) for at least 3 months prior to recruitment
5. presence of overweight or obesity with BMI \> 25 and a PG-SGA of class A.

Exclusion Criteria:

1. upper gastrointestinal involvement CD, fistulizing disease;
2. documented strictures based on sonographic findings or colonoscopy within the last year;
3. \> 1 small bowel resection;
4. colectomy;
5. presence of an ostomy;
6. antibiotic use in past 3-months;
7. pregnancy;
8. corticosteroids in the last 3 months.

Primary outcomes:
measure: BMI-A decrease in BMI of at least 1 BMI unit over the course of the intervention: Change is being assessed
timeFrame: Baseline and Week 12
measure: Fecal Calprotectin: Change is being assessed
timeFrame: Baseline and Week 12
measure: C Reactive Protien: Change is being assessed
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: 24 hour ASA food recalls: Change is being assessed.
timeFrame: Baseline and week 12
measure: Serum and fecal metabolomics: Change is being assessed
timeFrame: Baseline and Week 12
measure: Serum markers: Change is being assessed
timeFrame: Baseline and week 12
measure: Body Composition: Change is being assessed
timeFrame: Baseline and week 12
measure: Fecal microbiome: Change is being assessed
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: TRW building, Foothills, University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Maitreyi Raman, MD
role: PRINCIPAL_INVESTIGATOR
References: