The Effect of Diet on Disease Activity and Symptoms in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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The Mediterranean Diet Pattern (MDP) has been shown to have beneficial effects on the intestinal bacteria and the immune system in diseases like cancer and diabetes. The aim of this study is to determine if a MDP will have an impact on symptoms, intestinal bacteria and the immune system in Ulcerative Colitis (UC). Symptoms, blood and stool will be examined to determine if the MDP results in changes to the intestinal bacteria or immune system.

Detailed Description
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Few studies have found a single dietary factor as being protective or detrimental against inflammatory bowel disease (IBD), therefore novel diet approaches for the prevention and treatment of IBD are urgently needed. The Mediterranean Diet Pattern (MDP) is associated with improvements in health status and inflammatory markers in healthy individuals and rodent models of colitis. Reductions in inflammatory biomarkers and a normalization of the gut microbiota have been shown in patients with Crohn's disease following a MDP. To date, no studies have examined the effect of MDP on disease activity, inflammatory markers or the effects on the microbiome in ulcerative colitis (UC). This study will examine the effects of a MDP taken by patients with UC on 1) symptoms, clinical and quality of life endpoints and 2) on gut microbiome and fecal immune biomarkers. One hundred subjects and two subjects with UC will be randomly allocated to follow a MDP for 12 weeks or their usual diet (controls). Upon initiation, throughout and completion of each diet, symptoms, clinical and quality of life endpoints will be monitored. Fecal samples will be collected to assess pH, short-chain fatty acid concentrations, bacterial abundance and diversity.

Official Title
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The Effect of Diet Modification on Clinical Disease Activity, the Gut Microbiome and Immune Responses in Patients With Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Behavioral: Mediterranean diet pattern
* Behavioral: Habitual diet (control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ulcerative Colitis in clinical remission (partial Mayo score 0-1) Taking oral 5-ASA, methotrexate, azathioprine or 6-mecaptopurine as long as there have been no changes in dosage for 2 months prior to the start of the study Generally healthy besides having UC Agree not to use any dietary supplements, herbal treatments, prebiotics, probiotics or diet therapies within three weeks of the onset of the trial or during the study Exclusion Criteria: Using prednisone (or steroid equivalent) or biologics (i.e., infliximab, adalimumab, vedolizumab) at the time of enrollment Using antibiotics two weeks prior to or anytime during the study period Pregnancy, lactation or desire to become pregnant during the study period because we do not know if or how an unborn baby/fetus could be harmed History of colectomy or extensive colonic resection or disease is limited to the rectum Significant chronic disorders such as severe cardiac disease, significant renal failure, severe pulmonary disease (need for oxygen) Active gastrointestinal infection (e.g., C. difficile infection) Severe psychiatric disorder Unable or unwilling to consent Unable to comply with study requirements Presence of alcohol or drug abuse

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: Using a randomized, parallel treatment design, the effects of the Mediterranean diet pattern on symptoms, clinical disease activity, gut microbiome and fecal biomarkers in stable UC patients in remission will be examined. Using this design, we will compare the habitual diet (taken as a control diet) to the Mediterranean diet pattern taken by UC patients over a 12-week period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mediterranean Diet Pattern<br>Mediterranean diet pattern x 12 weeks. | Behavioral: Mediterranean diet pattern<br>* Subjects assigned to the Mediterranean diet pattern arm will receive nutrition advice from a Registered Dietitian (RD). The RD will meet with the subjects (in-person) to provide diet education at randomization, week 3 and week 6 of the intervention. Phone and e-mail follow-up will occur at week 2 and week 9 to provide cooking tips, recipes, videos and answer questions.<br>|
| Placebo Comparator: Habitual Diet<br>Habitual diet (control) x 12 weeks. | Behavioral: Habitual diet (control)<br>* Subjects assigned to follow their habitual group will be instructed to make no changes to their diet over 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simple Clinical Colitis Activity Index (SCCAI) | The SCCAI is a symptom-based disease activity index that uses six clinical parameters: daytime and nocturnal bowel frequency, urgency, amount of blood in the stool, well-being and extraintestinal manifestations. A reduction of SCCAI >1.5 is considered clinically significant and SCCAI score of <4 is indicative of remission. | Change from baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Inflammatory Bowel Disease Questionnaire (SIBDQ) | Quality of life improvement measured at baseline, week 3, week 6, week 9 and 12. | 12 weeks | 
| Fecal microbiota | Fecal microbiota measured by examining microbial taxa from stool at baseline and 12 weeks | 12 weeks | 
| Change in mucosal inflammation measured by fecal calprotectin | Change in mucosal inflammation will be measured by fecal calprotectin at baseline and week 12 | 12 weeks | 
| Change in serum marker of inflammation (serum CRP) | Change in markers of inflammation will be measured by serum CRP | 12 weeks | 
| Change in serum marker of inflammation (serum ferritin) | Change in markers of inflammation will be measured by serum ferritin | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mediterranean diet pattern, nutrition, diet intervention, disease activity, intestinal microbiome, inflammatory bowel disease