Crohn Disease
Conditions
Keywords
diet, inflammatory bowel disease, gut microbiome
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.
Interventions
OTHERSoy based diet
The diet will be based on the detailed descriptions according to the American Heart Association, US Food and Drug Administration (FDA), and the Soyfoods Association of North America Website, which all promote soy products as having beneficial nutrient profiles with a daily consumption of 25 grams or more of soy protein (average serving = 6.25 grams), upper limit of 50g.
OTHERNon-soy based diet
Diet of identical composition to the soy diet with the exception of soy.
Sponsors
Case Western Reserve University
University of California, Davis
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of Symptomatic Remission, Without Worsening of Any Existing Disease Activity During Study Period | 7 days | The primary aim will measure the Crohn's Disease Activity Index (CDAI) at the enrollment and end of study visit. CDAI scores can range from 0 to \~600 (A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease). Herein, a cut-off value of \<150 was selected so that most patients below this threshold would be rated by physicians as 'very well'. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point \[i.e., value at 7 days (post) minus value at baseline/enrollment (pre)\]. |
| Change in Fecal Myleoperoxidase (MPO) Activity | 7 days | Change in fecal myleoperoxidase (MPO) activity at day 7 vs day 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes to Functional Composition of Gut Microbiota | measured after the 7-day diet intervention | Secondary outcome will focus on changes to the functional composition of fecal gut microbiota, including bacterial butryate production after the diet intervention. |
| Percentage of Subjects Who Continue Diet Following Completion of Study | 6 months | To assess the percentage of patients who intend to continue the study diets when prepared food is no longer provided without cost, and the reasons for discontinuation of either diet (compared to resuming usual food habits). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFabio Cominelli, MD, PhD
Case Western Reserve University, School of Medicine, Gastroenterology
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Crohn's on Soy Diet Participants with Crohn's disease randomly assigned the Soy-based diet for 7 days. The diet will be preceded by a 12-hr overnight fast.
. | 16 |
| Crohn's on Non-Soy Diet Participants with Crohn's disease randomly assigned the non-Soy diet for 7 days. The diet will be preceded by a 12-hr overnight fast. | 15 |
| Healthy Controls on Soy Diet Healthy participants (without Crohn's disease) randomly assigned the Soy-based diet for 7 days. The diet will be preceded by a 12-hr overnight fast. | 14 |
| Healthy Controls on Non-Soy Diet Healthy participants (without Crohn's disease) randomly assigned the non-Soy diet for 7 days. The diet will be preceded by a 12-hr overnight fast. | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | Crohn's on Non-Soy Diet | Total | Crohn's on Soy Diet | Healthy Controls on Non-Soy Diet | Healthy Controls on Soy Diet |
|---|---|---|---|---|---|
| Age, Continuous | 48.53 years STANDARD_DEVIATION 11.3 | 41.55 years STANDARD_DEVIATION 13.71 | 46.43 years STANDARD_DEVIATION 12.72 | 35.2 years STANDARD_DEVIATION 14.25 | 36.14 years STANDARD_DEVIATION 13.05 |
| Body Mass Index | 30.23 kg/m^2 STANDARD_DEVIATION 6.46 | 28.93 kg/m^2 STANDARD_DEVIATION 6.32 | 29.15 kg/m^2 STANDARD_DEVIATION 6.34 | 28.74 kg/m^2 STANDARD_DEVIATION 5.78 | 28.32 kg/m^2 STANDARD_DEVIATION 6.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 59 Participants | 16 Participants | 14 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 3 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 48 Participants | 13 Participants | 11 Participants | 9 Participants |
| Region of Enrollment United States | 15 participants | 60 participants | 16 participants | 15 participants | 14 participants |
| Sex: Female, Male Female | 10 Participants | 41 Participants | 8 Participants | 12 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 8 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 1 / 16 | 0 / 15 | 1 / 14 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 | 0 / 14 | 0 / 15 |
Outcome results
Primary
Change in Fecal Myleoperoxidase (MPO) Activity
Change in fecal myleoperoxidase (MPO) activity at day 7 vs day 0.
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crohn's Patients on Soy Diet | Change in Fecal Myleoperoxidase (MPO) Activity | -0.691 ug/mg | Standard Deviation 1.471 |
| Crohn's Patients on Non-soy Diet | Change in Fecal Myleoperoxidase (MPO) Activity | 0.7336 ug/mg | Standard Deviation 1.483 |
| Healthy Controls on Soy Diet | Change in Fecal Myleoperoxidase (MPO) Activity | -0.0995 ug/mg | Standard Deviation 0.767 |
| Healthy Controls on Non-Soy Diet | Change in Fecal Myleoperoxidase (MPO) Activity | 0.5209 ug/mg | Standard Deviation 1.036 |
p-value: 0.0093ANOVA
Primary
Maintenance of Symptomatic Remission, Without Worsening of Any Existing Disease Activity During Study Period
The primary aim will measure the Crohn's Disease Activity Index (CDAI) at the enrollment and end of study visit. CDAI scores can range from 0 to \ 600 (A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease). Herein, a cut-off value of \<150 was selected so that most patients below this threshold would be rated by physicians as 'very well'. Change was calculated from two time points as the value at the later time point minus the value at the earlier time point \[i.e., value at 7 days (post) minus value at baseline/enrollment (pre)\].
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crohn's Patients on Soy Diet | Maintenance of Symptomatic Remission, Without Worsening of Any Existing Disease Activity During Study Period | -31.63 score on a scale | Standard Deviation 57.91 |
| Crohn's Patients on Non-soy Diet | Maintenance of Symptomatic Remission, Without Worsening of Any Existing Disease Activity During Study Period | -27.57 score on a scale | Standard Deviation 56.62 |
p-value: 0.469t-test, 2 sided
Secondary
Changes to Functional Composition of Gut Microbiota
Secondary outcome will focus on changes to the functional composition of fecal gut microbiota, including bacterial butryate production after the diet intervention.
Time frame: measured after the 7-day diet intervention
Secondary
Percentage of Subjects Who Continue Diet Following Completion of Study
To assess the percentage of patients who intend to continue the study diets when prepared food is no longer provided without cost, and the reasons for discontinuation of either diet (compared to resuming usual food habits).
Time frame: 6 months
Population: participants who responded to 6 month survey
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Crohn's Patients on Soy Diet | Percentage of Subjects Who Continue Diet Following Completion of Study | 8 Participants |
| Crohn's Patients on Non-soy Diet | Percentage of Subjects Who Continue Diet Following Completion of Study | 5 Participants |
| Healthy Controls on Soy Diet | Percentage of Subjects Who Continue Diet Following Completion of Study | 4 Participants |
| Healthy Controls on Non-Soy Diet | Percentage of Subjects Who Continue Diet Following Completion of Study | 1 Participants |
p-value: 0.2487Fisher Exact