Fasting-mimicking Diet in Treatment of Depressive Symptoms in IBD

Study Overview
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Brief Summary
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Inflammatory bowel disease (IBD) is a chronic illness characterized by inflammation of the intestine. Many individuals with IBD suffer from depressive symptoms and anxiety which can lead to a decreased quality of life, poor treatment compliance, and higher morbidity and mortality. The object of this clinical trial is to investigate the effects of a fasting mimicking diet in IBD patients who are suffering with symptoms of depression. Participants will carry out 3 cycles of a 5-day period of a plant-based low caloric diet or a plant-based caloric sufficient diet following by 3 weeks of eating normally. Effects of the dietary intervention on microbes in the gut, immune and metabolic function, and depressive symptoms will be measured. The overall goal is to develop a safe and effective treatment to improve mental health in patients with IBD by targeting the gut microbiome through dietary interventions.

Detailed Description
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The primary objective of this proof of principle study is to investigate the effects of a fasting mimicking diet on depressive symptoms in patients with inflammatory bowel disease. The specific aims of this project include: Determine whether a fasting-mimicking diet is effective in ameliorating depressive symptoms in patients with Crohn's disease or ulcerative colitis Determine if beneficial effects seen during the interventional period are sustained following cessation of fasting Examine effects of the intervention on the gut microbiome and metabolome

Official Title
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Effects of a Fasting Mimicking Diet on Depressive Symptoms in Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Other: Plant-based fasting-mimicking diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 65 years at the time of screening Diagnosis of Crohn's disease in clinical remission with Harvey Bradshaw Index (HBI<5) or diagnosis of ulcerative colitis in clinical remission with partial Mayo (pMayo<2) Suffering from mild-moderate depression with PHQ-9 ≥5 and ≤ 19 Exclusion Criteria: Subjects who are reliant on partial or total parenteral nutrition Subjects with prior gastrointestinal surgery and consequences such as short bowel syndrome, ostomy of small or large intestine, total colectomy, proctocolectomy, or ileoanal pouch Subjects with diabetes or celiac disease Subjects with a body mass index (BMI) lower than 18 Subjects suffering from malnutrition or at high risk of malnutrition assessed by a score of ≥6 on the abridged patient generated subjective global assessment (PGSGA) Subjects allergic to nuts Subjects currently on a fasting/intermittent type caloric restricted diet History of psychotic or bipolar disorders or experiencing suicidal thoughts Pregnant women, women who are breast feeding, or women planning on becoming pregnant Subjects with immune-compromised condition other than inflammatory bowel disease (e.g. AIDS, lymphoma) Subjects with severe uncontrolled cardiovascular or respiratory disease or active malignancy Unable to read English or provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an exploratory randomized double-blind parallel trial using a fasting-mimicking diet (FMD) in patients with inflammatory bowel disease (IBD) who are in clinical remission but experiencing depression
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasting-Mimicking Diet<br>Participants will be followed for 3 weeks for baseline assessment and then consume a plant-based fasting-mimicking diet for 5 days once a month for 3 months. | Other: Plant-based fasting-mimicking diet<br>* Participants will be on a low caloric plant-based diet or a caloric-sufficient plant-based diet for 3 x 5 day cycle each month followed by 3 weeks of eating normally for a total period of 3 months.<br>|
| Experimental: Caloric-Sufficient Diet<br>Participants will be followed for 3 weeks for baseline assessment and then consume a plant-based caloric-sufficient diet for 5 days once a month for 3 months. | Other: Plant-based fasting-mimicking diet<br>* Participants will be on a low caloric plant-based diet or a caloric-sufficient plant-based diet for 3 x 5 day cycle each month followed by 3 weeks of eating normally for a total period of 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Patient Health Questionnaire (PHQ-9) | A change in depressive symptoms as assessed through the Patient Health Questionnaire (PHQ)-9. [Min:0; Max 27; good to poor] | From baseline through 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Harvey-Bradshaw Index (HBI) in patients with Crohn's disease | Changes in disease status as assessed by HBI in Crohn's disease patients | From baseline through 12 and 24 weeks | 
| Changes in partial Mayo Score in patients with ulcerative colitis | Changes in disease status as assessed by partial Mayo Score in patients with ulcerative colitis | From baseline through 12 and 24 weeks | 
| Changes in clinical markers of disease | Changes in serum C-reactive protein (CRP) | From baseline through 12 and 24 weeks | 
| Changes in clinical markers of disease | Changes in fecal calprotectin | From baseline through 12 and 24 weeks | 
| Changes in levels of fatigue | Changes in level of fatigue as assessed by the inflammatory bowel disease-fatigue (IBD-F) self-assessment scale (0-20; low to high) | From baseline through 12 and 24 weeks | 
| Changes in general anxiety | Changes in general anxiety as assessed by the Hospital Anxiety and Depression scale (HADS) (0-21; low to high) | From baseline through 12 and 24 weeks | 
| Changes in quality of Life | Changes in quality of life as assessed by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (score 10-70, poor to good) | From baseline through 12 and 24 weeks | 
| Changes in weight | Changes in weight in kilograms | From baseline through 12 and 24 weeks | 
| Changes in body mass index (BMI) | Changes in BMI as assessed by weight in kilograms divided by the square of height in meters | From baseline through 12 and 24 weeks | 
| Changes in gene expression in peripheral blood mononuclear cells | Changes in immune function as assessed by changes in gene expression of peripheral blood mononuclear cells | From baseline through 12 and 24 weeks | 
| Changes in blood cytokines | Changes in plasma concentrations of cytokines (TNF, IL-6, IL-8, IFNγ, IL-1β, IL-9, IL-10, IL-12, IL-17, TGFβ) | From baseline through 12 and 24 weeks | 
| Changes in blood hormones | Changes in plasma concentrations of hormones (ghrelin, leptin, BDNF, GLP-1, glucagon, insulin) | From baseline through 12 and 24 weeks | 
| Changes in gut microbiome | Changes in gut microbiome as assessed by 16s rRNA analysis | From baseline through 12 and 24 weeks | 
| Changes in fecal short chain fatty acids | Changes in fecal concentrations of short chain fatty acids | From baseline through 12 and 24 weeks | 
| Changes in fecal bile acids | Changes in fecal concentrations of primary and secondary bile acids | From baseline through 12 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, diet, microbiome, fasting, inflammatory bowel disease