The Influence of a Fasting Mimicking Diet on Ulcerative Colitis

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03615690

Collaborator

(none)

Enrollment

Location

Arms

47.5

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Disease Diet Modification Ulcerative Colitis	Other: Fasting Mimicking Diet Other: Regular Diet	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Influence of a Fasting Mimicking Diet on Ulcerative Colitis

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Fasting Mimicking Diet

Three cycles of a 5-day reduced calorie diet

Other: Fasting Mimicking Diet

5 day reduced calorie diet

Placebo Comparator: Regular Diet Control Arm

Other: Regular Diet

Regular Diet

Outcome Measures

Primary Outcome Measures

Clinical response as per partial Mayo score [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.

Secondary Outcome Measures

Clinical remission as per partial Mayo score [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 [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 [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 [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). [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). [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. [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 [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 [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 [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).

Other Outcome Measures

Assessment of primary and key secondary endpoints at baseline versus 3 months after the start of Cycle 3. [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). [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. [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). [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.