The Influence of a Fasting Mimicking Diet on Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT03615690
• Recruitment Status: Recruiting
• First Posted: August 6, 2018
• Last Update Posted: April 22, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Sidhartha Ranjit Sinha, Stanford University

Tracking Information

• First Submitted Date: July 3, 2018
• First Posted Date: August 6, 2018
• Last Update Posted Date: April 22, 2022
• Actual Study Start Date: December 15, 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2020)

Clinical response as per partial Mayo score [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 decrease from baseline in the partial Mayo score of >= 2 points and either a rectal bleeding subscore of <=1 or a decrease in the rectal bleeding subscore of >=1 point, or achieving a partial Mayo score <2. The partial Mayo score consists of the subscores for stool frequency, rectal bleeding, and PGA, omitting endoscopy.

Original Primary Outcome Measures (submitted: July 30, 2018)

• Change in Fecal Calprotectin [ Time Frame: Comparison of calprotectin levels 1-3 days before Cycle 1, within 48 hours after Cycle 1 and three months after Cycle 3. ]
  P value of .05 or less will be considered statistically significant
• Change in C-Reactive Protein(CRP) [ Time Frame: Comparison of CRP 1-3 days before Cycle 1, within 48 hours after Cycle 1, 1-3 days before Cycle 2, within 48 hours after Cycle 3, 1 month after Cycle 3, and 3 months after Cycle 3 ]
  P value of .05 or less will be considered statistically significant
• Change in Erythrocyte Sedimentation Rate(ESR) [ Time Frame: Comparison of ESR 1-3 days before Cycle 1, within 48 hours after Cycle 1, 1-3 days before Cycle 2, within 48 hours after Cycle 3, 1 month after Cycle 3, and 3 months after Cycle 3 ]
  P value of .05 or less will be considered statistically significant
• Change in disease score(either Non-endoscopic Modified Mayo Score or CDAI) [ Time Frame: Comparison of disease score 1-3 days before Cycle 1, 5 days after Cycle 1, 5 days after Cycle 3 and 3 months after Cycle 3 ]
  Change in at least 2 points on the Mayo score/100 points on CDAI will define clinical success
• Change in SIBDQ Score [ Time Frame: Comparison of SIBDQ score 1-3 days before Cycle 1, 5 days after Cycle 1, 5 days after Cycle 3 and 3 months after Cycle 3 ]
  Quality of life score in IBD patients

Current Secondary Outcome Measures (submitted: April 17, 2020)

• Clinical remission as per partial Mayo score [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 partial Mayo score < 2 points. The partial Mayo score consists of the subscores for stool frequency, rectal bleeding, and PGA, omitting endoscopy.
• Clinical remission as per modified Mayo (mMayo) score [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 mMayo score <= 1 point, with rectal bleeding and stool frequency subscore of 0, and endoscopy subscore of 0 or 1. The mMayo score consists of the subscores for stool frequency, rectal bleeding, and endoscopy, omitting PGA.
• Clinical response as per mMayo score [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 decrease of the mMayo score of >=2 points and either a rectal bleeding subscore of <=1 or a decrease in the rectal bleeding subscore of >=1 point.
• Patient global assessment [ Time Frame: Assessed within 6 days after completing Cycle 3. 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 UC symptoms?" (Yes/No). No scale.
• Change in C-Reactive Protein (CRP). [ Time Frame: Comparison of CRP levels up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
  Change in the inflammatory marker CRP (if elevated at baseline).
• Change in Erythrocyte Sedimentation Rate (ESR). [ Time Frame: Comparison of ESR levels up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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).
• Change in Fecal Calprotectin. [ Time Frame: Comparison of calprotectin levels up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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).
• Effect of FMD on endoscopic outcomes [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 modified Mayo (mMayo) endoscopic subscore. The subscore ranges from 0 to 3 points with higher scores reflecting more severe disease.
• Symptomatic remission as per Patient Reported Outcome (PRO2) score [ Time Frame: Comparison of disease score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 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 Mayo stool frequency subscore of 0 or 1 and a Mayo rectal bleeding subscore of 0.
• Change in Short Inflammatory Bowel Disease questionnaire (SIBDQ) score [ Time Frame: Comparison of SIBDQ score up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
  Quality of life score in UC patients. Response to each of the questions is graded from 1 to 7 (1 being the worst situation and 7 the best).

Original Secondary Outcome Measures (submitted: July 30, 2018)

Change in Inflammatory cytokines and chemokines [ Time Frame: Comparison of cytokines/chemokines 1-3 days before Cycle 1, within 48 hours after Cycle 1, 1-3 days before Cycle 2, within 48 hours after Cycle 3, 1 month after Cycle 3, and 3 months after Cycle 3 ]

TNF-a, IL-17, etc.

Current Other Pre-specified Outcome Measures (submitted: April 17, 2020)

• Assessment of primary and key secondary endpoints at baseline versus 3 months after the start of Cycle 3. [ Time Frame: Comparison of endpoints up to 14 days before starting Cycle 1, and 3 months after the start of Cycle 3. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
  Outcomes 1 to 11 at additional time points.
• Changes in cytokines/chemokines and immune cell profiles using flow cytometry and mass cytometry (CyTOF). [ Time Frame: Comparison of cytokines/chemokines/immune cell profiles up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 3. 1 cycle of IRCD lasts 5 days and is administered once a month, followed by regular diet for the rest of the month. ]
  Cytokines/chemokines (e.g. TNF-alpha, IL-6, IL-10, IFN-gamma, α4β7, CCR1, and CCR9) and immune cell profiles.
• Differences in clinical markers of disease activity at baseline versus within 6 days after completing Cycle 1. [ Time Frame: Comparison of clinical markers up to 14 days before starting Cycle 1, and within 6 days after completing Cycle 1. 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).
• Changes in gut metabolites (including short-chain fatty acid and bile acid profiles) and microbiome profiles (using 16S rRNA/shotgun metagenomics). [ Time Frame: Comparison of characteristics up to 14 days before Cycle 1, within 6 days after completing Cycle 3, and 3 months after start of Cycle 3. 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Influence of a Fasting Mimicking Diet on Ulcerative Colitis
• Official Title: The Influence of a Fasting Mimicking Diet on Ulcerative Colitis
• Brief Summary: The purpose of this study is to see how a diet that mimics fasting effects inflammation in patients with mild to moderate Ulcerative Colitis (UC). 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 UC are very limited. Fasting mimicking diets (FMD) 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 three cycles of a five-day period of the fasting mimicking diet, and may provide rationale for its use to treat UC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Inflammatory Bowel Disease
• Diet Modification
• Ulcerative Colitis

Intervention

• Other: Fasting Mimicking Diet
  5 day reduced calorie diet
• Other: Regular Diet
  Regular Diet

Study Arms

• Experimental: Fasting Mimicking Diet
  Three cycles of a 5-day reduced calorie diet
  Intervention: Other: Fasting Mimicking Diet
• Placebo Comparator: Regular Diet Control Arm
  Intervention: Other: Regular Diet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 29, 2019): 75
• Original Estimated Enrollment (submitted: July 30, 2018): 40
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Mild to moderate Ulcerative Colitis on the partial Mayo Score out of 9 (score between 2 to 7)
• Age of 18-70 at start of study (inclusive)

Exclusion Criteria:

• Women who are pregnant or 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 as defined by the patient's physician, 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 FMD 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 caloric 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, hemi- or total colectomy, proctocolectomy, ileoanal pouch will be excluded.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03615690
• Other Study ID Numbers: IRB 47075
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sidhartha Ranjit Sinha, Stanford University
• Original Responsible Party: Sidhartha R Sinha, Stanford University, Assistant Professor of Medicine
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Stanford University
• Verification Date: April 2022