Clinical trial NCT04065048: A Dietary Intervention Study on the Microbiome in Crohn's Disease Patients
Official title: A Single-center Open-label Study to Determine the Effect of Diet on Microbiome Signatures in Crohn's Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn Disease
Keywords: diet
inflammatory bowel disease
gut microbiome
Lead sponsor: Case Western Reserve University
Sponsor class: OTHER
Collaborators: name: University of California, Davis
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: University Hospitals Cleveland Medical Center
First posted: 2019-08-22
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an open label single center study to compare the effect of a soy-based diet or an identical diet without soy on the composition and metabolite production of gut bacteria in Crohn's disease (CD) patients in remission or active disease, and in healthy controls. Crohn's subjects will be pre-screened by the treating gastroenterologist for eligibility criteria during their normally scheduled appointment. The treating gastroenterologist will ask suitable patients whether they are interested in participating in the described dietary intervention study during the patient appointment. Initial verbal consent will be obtained by the treating gastroenterologist. Healthy controls will be recruited in the same manner, as well as via a hospital flyer advertisement. Subjects will then be contacted by the study investigator to schedule a screening visit (visit 1) and if study eligibility is confirmed, and informed consent provided, enrolled into the study.
Primary purpose: OTHER

Brief summary: This protocol is designed to compare the effectiveness of a soy-based diet or identical diet without soy given to patients with Crohn's disease (CD) in remission, patients with active CD, or healthy controls. The assigned diet will be compared to participant 'baseline' (pre-diet) in terms of its ability to change the gut bacteria and fecal butyrate, an important short-chain fatty acid (SCFA) that limits bowel inflammation, a characteristic of this debilitating disease.

Detailed description: The inflammatory bowel disease (IBD) subtype, Crohn's disease (CD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Although the precise etiology of IBD is not known, evidence suggests that environmental factors, including diet, contribute to its pathogenesis. A soy-based diet has been demonstrated to have numerous health benefits. This single-center open-label study will compare the effectiveness of a soy-based diet or an identical diet without soy to change the gut microbiota composition and fecal butyrate concentration to that of baseline (pre-diet) in patients with CD (remission or active disease) and healthy control subjects without CD. Participants will follow either a soy-based diet or an identical diet without soy to which they will be randomized for 7 days. No data collection or other study procedures will take place until the potential participant provides written informed consent to participate in the research study. The informed consent, screening, enrollment, and baseline data collection which make up visit 1 can occur on the same day or be completed across several days.

Eligibility criteria: Inclusion Criteria:

* CD subjects: Documented diagnosis of Crohn's disease. Control subjects: no documented diagnosis of CD.
* CD subjects: Harvey Bradshaw Index (HBI) score \<4 ('CD remission'), or with HBI score \>8 ('CD moderate disease')
* Capable of providing consent to participate
* Access to technology that permits the daily completion of study related activities
* Able to receive and have an adult sign for food shipments delivered to a work or home environment.
* Negative pregnancy test at screening visit in females of childbearing potential
* Able to take oral nutrition and medication intake for 3 months prior to and at time of study enrolment.
* 'CD remission' subjects: No change in 'IBD related' medications within 8 weeks prior to normally scheduled appointment with treating gastroenterologist (pre-screening): biologics, immunosuppressants, corticosteroids.

Exclusion Criteria:

* Short bowel syndrome.
* Hospitalized patients
* Body mass Index \<19 kg/m or ≥35.
* Known clinically significant liver/gallbladder/pancreatic disease/dysfunction
* Individuals who lack consent capacity, including the mentally ill, prisoners, cognitively impaired participants, dementia patients.
* Uncontrolled Diabetes Type I type II
* Known drug abuse.
* Known parasitic disease of the digestive system. symptomatic intestinal stricture.
* Presence of an ostomy.
* Known concurrent malignancy.
* Other conditions that would be a contraindication to and of the study diets (e.g. Soy, peanut, wheat, gluten allergy.) or preclude the participant from completing the study
* Start of new 'IBD related' medications within 8 weeks prior to enrollment: biologics, immunosuppressants, corticosteroids.
* Documented C difficile colitis within four weeks of screening
* Well-founded doubt about the patient's cooperation.
* Existing pregnancy or lactation.
* Current participation in another diet intervention, simultaneous participation in another clinical trial, or participation in any other dietary intervention trial within the last 30 days.
* History of \<3 natural bowel movements per week.
* Unable to access to technology that permits the daily completion of study related activities.
* Currently consuming a soy-based diet

Primary outcomes:
measure: Maintenance of Symptomatic Remission, Without Worsening of Any Existing Disease Activity During Study Period
timeFrame: 7 days
measure: Change in Fecal Myleoperoxidase (MPO) Activity
timeFrame: 7 days
Secondary outcomes:
measure: Changes to Functional Composition of Gut Microbiota
timeFrame: measured after the 7-day diet intervention
measure: Percentage of Subjects Who Continue Diet Following Completion of Study
timeFrame: 6 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Digestive Health Institute
state: Ohio
Study officials:
affiliation: Case Western Reserve University, School of Medicine, Gastroenterology
name: Fabio Cominelli, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011 Oct 7;334(6052):105-8. doi: 10.1126/science.1208344. Epub 2011 Sep 1.
citation: David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
citation: Thia K, Faubion WA Jr, Loftus EV Jr, Persson T, Persson A, Sandborn WJ. Short CDAI: development and validation of a shortened and simplified Crohn's disease activity index. Inflamm Bowel Dis. 2011 Jan;17(1):105-11. doi: 10.1002/ibd.21400.