Obesity
Conditions
Brief summary
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.
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.
Interventions
OTHERNormal 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.
OTHERHigh 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.
OTHERLow 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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 high 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 | Change in 48h-fecal bile acid excretion (μmol/L) between baseline and low fat diet |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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.
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. | 8 |
| 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.
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.
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.
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. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Obese Participants | Total | Normal Weight Participants |
|---|---|---|---|
| Age, Continuous | 38 years STANDARD_DEVIATION 12 | 36 years STANDARD_DEVIATION 10 | 33 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment United States | 8 participants | 16 participants | 8 participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
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
Time frame: Baseline to approximately day 7 of week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Participants | Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and High Fat Diet | 543 (μmol/L)/48 hour | Standard Deviation 313 |
| Normal Weight Participants | Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and High Fat Diet | 344 (μmol/L)/48 hour | Standard Deviation 445 |
Primary
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
Time frame: Baseline to approximately day 7 of week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Participants | Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and Low Fat Diet | 717.6 (μmol/L)/48 hour | Standard Deviation 666.1 |
| Normal Weight Participants | Change in 48h-fecal Bile Acid Excretion (μmol/L) Between Baseline and Low Fat Diet | 297 (μmol/L)/48 hour | Standard Deviation 237.3 |