Characterization of Bile Acid Pathway in Obesity

It is unknown whether the bile acid pathway is altered in obesity. This study is designed to compare obesity and health to determine if the bile acid pathway differs depending on health state.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Normal Diet; Other: High Fat Diet; Other: Low Fat Diet

Detailed Description

This is a single center study involving diet intervention, including healthy obese and healthy normal weight participants. Participants will maintain their normal diet for 1 week, eat a high fat and high calorie diet for 1 week, return to their normal diet for 1 week, and eat a low fat and low calorie diet for 1 week, to study the effect of diet on the bile acid pathway in normal weight and obesity. During their first normal diet week, the high calorie week, and the low calorie week, blood samples will be collected at defined times to measure cholesterol, glycemia, Fibroblast Growth Factor 19 (FGF-19), Bile Acid (BA), C4, and incretins (GLP-1 (glucagon-like peptide-1), peptide tyrosine tyrosine (PYY 3-36)) fasting levels and responses to the meal. Stool samples will be collected for 48 hour BA excretion.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Normal Weight Inclusion Criteria:

• Women of childbearing potential will have negative pregnancy tests within 48 hours of enrollment
• BMI: 18.5-25 kg/m2

Obese Inclusion Criteria:

• Women of childbearing potential will have negative pregnancy tests within 48 hours of enrollment
• BMI: ≥ 30 kg/m2

Exclusion Criteria for both Normal Weight and Obese Participants:

• History of abdominal surgery including cholecystectomy and other than appendectomy, Caesarian section or tubal ligation.
• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption, e.g., orlistat, phentermine.
• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), a self-administered alcoholism screening test (AUDIT-C) and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a HAD score >11 or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up. The AUDIT-C is a 3-item alcohol screening questionnaire that reliably identifies participants who are hazardous alcohol drinkers or have active alcohol use disorders. In men, a score of 4 or more is above the recommended limits will be reviewed by study personnel. In women, a score of 3 or more is above the recommended limits will be reviewed by study personnel. However when the points are above recommended limits, the provider will review the patient's alcohol intake over the past few months to confirm accuracy and determine study eligibility..
• Intake of medication, whether prescribed or over the counter (except multivitamins), within 7 days of the study. Exceptions are birth control pill, estrogen replacement therapy, and thyroxin replacement therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Obese Participants; Participants will be on each diet for one week prior to collection of laboratory samples. Participants will be on their normal diet on weeks 1 and 3, on the high fat diet on week 2, and low fat diet on week 4.	Other: Normal Diet; The normal diet will consist of the participants' normal eating habits, and will be tracked by a food log. The participants will be on their normal diet during week 1 and week 3.; Other: High Fat Diet; The high fat diet will consist of 2700 kcal, 100g total fat (33%), 300mg cholesterol, 350g carbohydrates (52%), and 100g protein (15%). The participants will be on this diet during week 2.; Other: Low Fat Diet; The low fat diet will consist of 1200 kcal, 26g fat (20%), 78mg cholesterol, 150g carbohydrates (50%), and 100g protein (30%). The participants will be on this diet during week 4.
Active Comparator: Normal Weight Participants; Participants will be on each diet for one week prior to collection of laboratory samples. Participants will be on their normal diet on weeks 1 and 3, on the high fat diet on week 2, and low fat diet on week 4.	Other: Normal Diet; The normal diet will consist of the participants' normal eating habits, and will be tracked by a food log. The participants will be on their normal diet during week 1 and week 3.; Other: High Fat Diet; The high fat diet will consist of 2700 kcal, 100g total fat (33%), 300mg cholesterol, 350g carbohydrates (52%), and 100g protein (15%). The participants will be on this diet during week 2.; Other: Low Fat Diet; The low fat diet will consist of 1200 kcal, 26g fat (20%), 78mg cholesterol, 150g carbohydrates (50%), and 100g protein (30%). The participants will be on this diet during week 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and High Fat Diet	Change in 48h-fecal bile acid excretion (μmol/L) between baseline and high fat diet	Baseline to approximately day 7 of week 2
Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and Low Fat Diet	Change in 48h-fecal bile acid excretion (μmol/L) between baseline and low fat diet	Baseline to approximately day 7 of week 4

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Andres J Acosta Cardenas, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2017
• Primary Completion (Actual): October 9, 2021
• Study Completion (Actual): October 9, 2021

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: November 9, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 16-007060; K23DK114460 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No