UC Cohort - The Influence of Diet on Gut Microbiotas

Study Overview
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Brief Summary
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The purpose of this research is to determine if different diets have different effects on the inflammation in the colon.

Official Title
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UC Cohort - The Influence of Diet on Host Physiology and Disease Across Diverse Human Gut Microbiotas

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Dietary Supplement: High Protein and Low Fiber Diet
* Dietary Supplement: Low Protein and High Fiber Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years old Ability to give informed consent Diagnosis of ulcerative colitis Moderate UC disease activity defined by a Mayo Score of >6 with endoscopic score of 2 On a baseline diet characterized by: Fiber intake of < 15g/day > 18% of daily calories from protein Exclusion Criteria: Prior history of gastrointestinal surgeries (except appendectomy and cholecystectomy) Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) Use of NSAIDs or aspirin and unable or unwilling to stop taking two weeks prior to permeability test and for the duration of the study Use of osmotic laxatives and unable or unwilling to stop taking one week prior to permeability test and for the duration of the study Use of oral corticosteroids and unable or unwilling to stop use of oral corticosteroids within the previous 2 weeks and for the duration of the study Multiple dietary restrictions or unable/unwilling to alter dietary protein or dietary fiber. Unwilling to stop ingestion of alcohol and artificial sweeteners such as Splenda™ (sucralose), Nutrasweet™ (aspartame), sorbitol, xylitol, lactulose, or mannitol 2 days before and during the permeability testing days, e.g. foods to be avoided are sugarless gums or mints and diet beverages Unwilling to stop stenuous exercise (running >5 miles or equivalent) one week prior to the permeability tests Bowel preparation for colonoscopy less than one week prior to completion of the first stool kit and permeability test and flexible sigmoidoscopy and upper endoscopy Pregnancy or plan to become pregnant during the study time frame Vulnerable adult Known bleeding disorders or takes medications that increase risk of bleeding from mucosal biopsies Use of oral antibiotic(s) within the past 4 weeks (can be enrolled after 4-week washout period) Use of commercial probiotic formulations and unwilling to stop for the duration of the study Diagnosis of diabetes Any other disease(s), condition(s) or habits(s) that would interfere with completion of study, or in the judgment of the investigator would potentially interfere with compliance to this study or would adversely affect study outcomes

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Protein and Low Fiber Group<br>Subjects will consume a high protein and low fiber diet for 8 weeks | Dietary Supplement: High Protein and Low Fiber Diet<br>* Protein intake will be increased to be >40% calories from protein, and the fiber intake will remain <15gm/day.<br>|
| Experimental: Low Protein and High Fiber Group<br>Subjects will consume a low protein and high fiber diet for 8 weeks | Dietary Supplement: Low Protein and High Fiber Diet<br>* Increase fiber intake up to 40gms of fiber with a requirement to increase at least 15gms above baseline fiber, with 50-75% of total fiber intake from psyllium husk. Subjects will be allowed to slowly increase fiber every two days to reach goal by end of week 1. The total protein will be reduced to <10% total calories from protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in endoscopic Mayo score for ulcerative colitis inflammation | Measured from unprepped, non-sedated flexible sigmoidoscopy by decrease in Mayo score with a decrease of at least 1 point on the endoscopic subscore or absolute endoscopic subscore of 0-1). | 8 weeks | 
| Clinical remission derived from patient reported outcomes | Defined as a Mayo score ≤2 and no sub-scores with a value greater than 1 is a secondary endpoint. This what the patient reports for stool frequency and reporting of any blood in the stool | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal inflammation determined from blood and stool samples | Measures C-reactive protein from blood samples and fecal calprotectin from stool samples | 8 weeks | 
| Urinary excretion of lactulose and 13C-Mannitol | Small Bowel and Colonic Permeability by Urinary Excretion of Lactulose and 13C-Mannitol after Oral Ingestion of lactulose and 13C mannitol (5:1 ratio by mass). The 0-2h urine most closely reflects small intestinal permeability and 8-24h urine reflects colonic permeability. HPLC-tandem mass spectrometry will be used for detection of the sugars. The results will be expressed as the ratio of percentage excretion of the ingested dose of lactulose and mannitol in urine. | 8 weeks |