Obesity
Conditions
Keywords
Body composition, Feeding study, Ketogenic diet, Weight loss, Energy Expenditure
Brief summary
This study will evaluate the effects of dietary carbohydrate and sugar consumption, independent of energy content, on body fatness and metabolism in a rigorous feeding study.
Detailed description
Many people with obesity can lose weight for a few months, but most have difficulty maintaining weight loss over the long term. Extensive research has shown that weight loss elicits biological adaptations - including a decline in energy expenditure and an increase in hunger - that promote weight regain. However, this observation leaves unanswered why average body weight has recently increased among populations that are mostly genetically stable. According to the Carbohydrate-Insulin Model, increased consumption of processed carbohydrates during the low-fat diet era of the last 40 years has raised the average body weight being defended by biological mechanisms on a population basis. Specifically, the investigators hypothesize that diets high in total carbohydrate (with or without added sugar) acting through increased insulin secretion, alter substrate partitioning toward storage in body fat, leading to increased hunger, slowing metabolism, and accumulation of body fat. To test this hypothesis, the investigators plan a randomized-controlled feeding study involving 125 adults with obesity. During the run-in phase, participants will be given a hypocaloric very-low-carbohydrate (VLC) diet, with adjustment of energy intake to produce 15 ± 3% weight loss over 3 to 4 months on an outpatient basis. After weight stabilization, participants will be admitted to a residential center for 13 weeks. During the first 3 weeks, energy intake and expenditure will be closely monitored during weight-loss maintenance. Then, energy intake will be individually locked at levels equal to energy expenditure and participants will be administered one of three randomly-assigned test diets for 10 weeks. The test diets include VLC, High Carbohydrate-Low Sugar (HC-LS), and High Carbohydrate-High Sugar (HC-HS).
Interventions
BEHAVIORALFeeding Study
Food provision throughout the study: 1) Run-In Phase (VLC diet, weight loss); 2) Residential Phase (3 different test diets, weight-loss maintenance).
Sponsors
Indiana University
University of Alabama at Birmingham
Framingham State University
Baylor University
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Assessors conducting analyses of biospecimens, laboratory personnel, DXA technologists, and research nurses were blinded to random group assignment. They were not involved in the randomization process or any aspects of the intervention. The statistical team worked with masked labels for the diet arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 to 50 years * BMI ≥ 27 kg/m2 * Weight ≤ 350 lb * Medical clearance from a primary care provider * Willingness to follow a VLC weight-loss diet * Willingness to reside in a research unit for 3 months and eat/drink only provided study foods and beverages * No major food allergies or aversions * Willingness to obtain seasonal flu shot or provide documentation of flu shot for current flu season (winter/spring cohort only) * Willingness to discuss work options (e.g., remote work) with employer, and make appropriate arrangements prior to the Residential phase.
Exclusion criteria
* Change in body weight ≥ 10% during prior 6 months * Specialized diets (e.g., for medical or religious reasons) * Chronic use of any medication or dietary supplement that could affect study outcomes (e.g., insulin, metformin, thyroxine) * Current smoking (1 cigarette in the last week) * Greater than moderate alcohol consumption (\> 14 drinks/wk) or history of binge drinking (≥5 drinks in 1 day within past 6 months) * Physician diagnosis of a major medical illness or eating disorder * History of kidney stones * Laboratory tests: ALT\>2x upper limit; abnormal HgA1c; abnormal TSH; abnormal creatinine; abnormal uric acid (using the male upper limit for both sexes) * Failed criminal offender background check or sex offender background check * Use of recreational drugs * Current diagnosis or history of kidney stones, gout, or gall stones; or removal of gall bladder * Exercise restrictions or at high risk for complications during exercise Female-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body fat mass | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Body composition assessed using a multi-component model |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Adiponectin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Adipokine |
| Total energy expenditure (TEE) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed using doubly labeled water methodology |
| Resting energy expenditure (REE) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by indirect calorimetry using respiratory gas exchange methodology with a ventilated hood system |
| Physical activity level, (moderate to vigorous) | Measurements made daily during 2 weeks at PWL, 2 weeks at END, and alternating non-assessment weeks of the residential phase and integrated into a unified outcome | Total minutes of moderate- to vigorous-intensity physical activity, assessed by accelerometry |
| Insulin sensitivity | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by frequently-sampled oral glucose tolerance test \[OGTT\], calculated using plasma insulin and glucose values |
| Insulin secretion | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by frequently-sampled oral glucose tolerance test \[OGTT\], using plasma insulin at 30 minutes following the dose of dextrose |
| Glycemic control | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Hemoglobin A1c \[HbA1c\] |
| Total cholesterol | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Chronic disease risk factor |
| HDL-cholesterol | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Chronic disease risk factor |
| LDL-cholesterol | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Chronic disease risk factor |
| Non-HDL cholesterol | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Chronic disease risk factor |
| Triglycerides | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Chronic disease risk factor |
| Plasminogen Activator Inhibitor-1 [PAI-1] | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Indicator of coagulopathy |
| High-sensitivity C-reactive protein [hsCRP] | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Indicator of chronic inflammation |
| Uric acid | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Indicator of risk for kidney stones, measured in blood |
| Systolic blood pressure | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by auscultation, mmHg |
| Diastolic blood pressure | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by auscultation, mmHg |
| Thyroxine (T4) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Thyroid function |
| Free T4 | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Thyroid function |
| Thyroid stimulating hormone [TSH] | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Thyroid function |
| Insulin-like growth factor-1 [IGF-1] | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Growth hormone action |
| Urine cortisol | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Stress hormone, assessed using 24-hour urine collection |
| Urine catecholamines | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Stress hormone, assessed using 24-hour urine collection |
| Leptin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Adipokine |
| High-molecular weight adiponectin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Adipokine |
| Sleep | Measurements made daily during 2 weeks at PWL, 2 weeks at END, and alternating non-assessment weeks of the residential phase and integrated into a unified outcome | Total sleep time, sleep onset latency, wake after sleep onset, and sleep efficiency, assessed by accelerometry |
| Blood glucose | Measurements made daily during residential phase (0 to 10 weeks) and integrated into a unified outcome | Assessed by continuous glucose monitoring (CGM) |
| Ghrelin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Hormonal Control of Appetite |
| Body Circumference | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed using a 3D body scan |
| Post-prandial energy expenditure and respiratory quotient | Single assessment in weeks 6 to 8 of residential study | Optional testing, assessed by indirect calorimetry using respiratory gas exchange |
| Activation of insulin signaling pathways | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed by immunohistochemistry of phosphorylated insulin receptor and signaling proteins |
| Lean body mass | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Assessed using a multi-component model (difference between total body mass and fat mass) |
| Body weight | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Anthropometrics, assessed by calibrated scale, in kilograms (kg) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Lipoprotein particle subfraction distribution | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Fibrinogen | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Interleukin-6 (IL-6) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Reverse triiodothyronine (rT3) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Insulin-like growth factor-binding protein 3 (IGF-BP3) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Luteinizing hormone (LH) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Follicle stimulating hormone (FSH) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Estradiol (E2) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Testosterone (TST, total) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Testosterone (TST, free) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Metabolomics profile | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Biomarker of cholesterol synthesis | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Biomarker of cholesterol absorption | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Gut microbiome | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| Demographics (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Body composition (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Measure of glucose homeostasis (insulin-30) (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Measure of glucose homeostasis (glycemic control) (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Obesity related genetic risk (mediator/modifier) | Pre-weight loss baseline | Baseline covariate |
| Physical activity level (moderate to vigorous) (mediator/modifier) | Measurements made daily during 2 weeks at PWL, 2 weeks at END, and alternating non-assessment weeks of the residential phase and integrated into a unified outcome | Time varying covariate for total minutes of moderate to vigorous intensity physical activity, assessed by accelerometry. |
| Sex Hormone-Binding Globulin (SHBG) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analysis of archived specimen |
| Urinary nitrogen | End of residential (END, 10 weeks) | Archived for future analysis |
| Glucagon-like peptide-1 (GLP-1) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived samples |
| Glucose-dependent insulinotropic polypeptide (GIP) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived samples |
| Glucagon | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived samples |
| Oxytocin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived samples |
| Oxyntomodulin | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived samples |
| MicroRNA | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
| 1,5-anhydroglucitol (1,5-AG) | Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) | Possible future analyses of archived specimen |
Countries
United States
Outcome results
None listed