Effects of an Intermittent Reduced Calorie Diet on Crohn's Disease

• ClinicalTrials.gov Identifier: NCT04147585
• Recruitment Status: Recruiting
• First Posted: November 1, 2019
• Last Update Posted: May 4, 2021
• Sponsor: Stanford University
• Information provided by (Responsible Party): Sidhartha Ranjit Sinha, Stanford University

Study Description

Brief Summary:

The purpose of this study is to see how an Intermittent Calorie Reduced Diet (IRCD) that mimics fasting effects inflammation in patients with mild to moderate Crohn's disease (CD). The diet may allow users to receive the benefits of fasting while also being able to enjoy food (the ingredients of which are GRAS (generally recognized as safe) by the Food and Drug Administration (FDA). Research on dietary interventions and CD are very limited. Diets that mimick fasting have been studied with support of the National Institute of Health and published in leading journals. This research investigates whether markers of inflammation decrease and/or quality of life increases after five-day periods of the IRCD, and may provide rationale for its use to treat CD.

Condition or disease	Intervention/treatment	Phase
Inflammatory Bowel Diseases; Crohn Disease; Diet Modification	Other: Intermittent Reduced Calorie Diet (IRCD)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of an Intermittent Reduced Calorie Diet on Crohn's Disease
• Actual Study Start Date: December 18, 2019
• Estimated Primary Completion Date: July 14, 2022
• Estimated Study Completion Date: October 14, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention Arm; Three cycles of a 5-day Intermittent Reduced Calorie Diet	Other: Intermittent Reduced Calorie Diet (IRCD); Three cycles of a 5-day Intermittent Reduced Calorie Diet over three months.
No Intervention: Control Arm; Regular Diet

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Clinical response as per CDAI (70 points) [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as reduction of the CDAI of at least 70 points or achieving a CDAI score ≤ 150.

Secondary Outcome Measures :

1. Number of Participants with Clinical remission as per CDAI [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as a CDAI score ≤ 150.
2. Number of Participants with Clinical response as per CDAI (100 points) [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as reduction of the CDAI of at least 100 points or achieving a CDAI score ≤ 150.
3. Number of Participants with Clinical response as per CDAI (70 points) [ Time Frame: Assessed 3 months after 3rd cycle. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as reduction of the CDAI of at least 70 points or achieving a CDAI score ≤ 150.
4. Change in C-reactive protein (CRP) at baseline versus after 3rd cycle of IRCD (or control at corresponding time point) in both IRCD and control group. [ Time Frame: Baseline versus within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Change of the inflammatory marker CRP if elevated at baseline.
5. Change in Erythrocyte Sedimentation Rate (ESR) at baseline versus after 3rd cycle of IRCD (or control at corresponding time point) in both IRCD and control group. [ Time Frame: Baseline versus within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Change of the inflammatory marker ESR if elevated at baseline.
6. Change in fecal calprotectin at baseline versus after 3rd cycle of IRCD (or control at corresponding time point) in both IRCD and control group. [ Time Frame: Baseline versus within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Change of the inflammatory marker fecal calprotectin if elevated at baseline.
7. Number of Participants with Clinical remission as per Patient Reported Outcome (PRO) score [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as average worst daily abdominal pain score of ≤ 1 (using a 4-point scale, 0-3) and a loose/watery stool (Bristol Type 6 or 7) frequency score of <=3.
8. Patient global assessment [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   "Do you believe you are in remission from your CD symptoms?" (Yes/No). No scale.
9. Effect of IRCD on endoscopic outcomes [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Changes in Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD). SES-CD scores range from 0 to 56 and higher scores indicate more severe disease.
10. Effect of IRCD on patient quality of life: Short Inflammatory Bowel Disease questionnaire (SIBDQ) [ Time Frame: Assessed within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
    Changes in SIBDQ. Response to each of the questions is graded from 1 to 7 (1 being the worst situation and 7 the best).

Other Outcome Measures:

1. Number of Participants with Clinical remission as per CDAI [ Time Frame: Assessed 3 months after 3rd cycle. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as a CDAI score ≤ 150.
2. Number of Participants with Clinical response as per CDAI (100 points) [ Time Frame: Assessed 3 months after 3rd cycle. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Defined as reduction of the CDAI of at least 100 points or achieving a CDAI score ≤ 150.
3. Changes in clinical markers of disease activity [ Time Frame: At baseline versus 3 months after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Clinical markers of disease activity are CRP, ESR, and fecal calprotectin if elevated at baseline.
4. Effect of IRCD on patient quality of life: Short Inflammatory Bowel Disease questionnaire (SIBDQ) [ Time Frame: Assessed 3 months after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Changes in SIBDQ. Response to each of the questions is graded from 1 to 7 (1 being the worst situation and 7 the best).
5. Changes in clinical markers of disease activity [ Time Frame: At baseline versus within 6 days after 1st cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Clinical markers of disease activity are CRP, ESR, and fecal calprotectin if elevated at baseline.
6. Changes in cytokines/chemokines and immune cell profiles [ Time Frame: At baseline versus within 6 days after 3rd cycle of IRCD. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Using flow cytometry and mass cytometry (CyTOF)
7. Changes in gut metabolites (including short-chain fatty acid and bile acid profiles) and microbiome profiles (using 16S rRNA/shotgun metagenomics) [ Time Frame: At baseline versus within 6 days after 3rd cycle of IRCD and 3 months after 3rd cycle. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
   Gut metabolites include short-chain fatty acid and bile acid profiles.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Mild to moderate Crohn's disease (CDAI score 151-450)
• Between the ages of 18-70 (inclusive)

Exclusion Criteria:

• Women who are pregnant, nursing or expect to be pregnant
• Individuals allergic to nuts
• Individuals with a body mass index (BMI) lower than 18
• Individuals diagnosed with a serious medical condition (unless approved in writing by a physician)
• Individuals who have been severely weakened by a disease or medical procedure
• Individuals who are taking medication which may not be safely consumed with a calorie restricted diet
• Individuals with diabetes who are taking anti-diabetic drugs associated with risk of hypoglycemia
• Individuals with more than mild-moderate cardiovascular disease or life-threatening cancer (as determined by patient's physician) unless approved by a physician
• Individuals with history of severe cardiac disease (particularly uncompensated congestive heart failure NYHA grade 2 or more or LVEF < 40%)
• Individuals with a history of syncope
• Individuals with dietary needs incompatible with the IRCD meal plan
• Individuals with liver or kidney disorders that may be affected by very low glucose and protein content of the diet
• Patients on a calorie restricted diet will also be excluded
• Patients with relevant prior gastrointestinal surgery and consequences such as short bowel syndrome, ostomy of small or large intestine,total colectomy, proctocolectomy, ileoanal pouch will be excluded (not excluded are patients with resection of terminal ileum, resection of short strictures of the small intestine, hemicolectomy).

Contacts and Locations

Contacts

Contact: Touran Fardeen; 6507367311; tfardeen@stanford.edu

Locations

United States, California

Stanford University; Recruiting

Palo Alto, California, United States, 94305

Contact: Touran Fardeen tfardeen@stanford.edu

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Sidhartha R Sinha, MD; Stanford University

More Information

• Responsible Party: Sidhartha Ranjit Sinha, Assistant Professor of Medicine (Gastroenterology and Hepatology), Stanford University
• ClinicalTrials.gov Identifier: NCT04147585
• Other Study ID Numbers: IRB 53161
• First Posted: November 1, 2019
• Last Update Posted: May 4, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidhartha Ranjit Sinha, Stanford University:

IBD; Crohn's disease; Diet; Fasting; Intermittent Reduced Calorie Diet; CD; intermittent fasting; FMD

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases