FB4 (Framingham, Boston, Bloomington, Birmingham, and Baylor)
- Conditions
- Obesity
- Interventions
- Behavioral: Feeding Study
- Registration Number
- NCT03394664
- Lead Sponsor
- Boston Children's Hospital
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 166
- 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.
- 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 exclusion criteria:
- Menopausal
- Any change in birth control medication during the 3 months prior to enrollment
- Pregnancy or lactation during the 12 months prior to enrollment, or intent to become pregnant during study participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Very-Low Carbohydrate Diet Feeding Study Feeding study. Dietary composition (approximately): 75% fat High-Carbohydrate High-Sugar Diet Feeding Study Feeding study. Dietary composition (approximately): 25% fat, 20% added sugars. High-Carbohydrate Low-Sugar Diet Feeding Study Feeding study. Dietary composition (approximately): 25% fat 0% added sugars.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
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
Total Adiponectin 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
Trial Locations
- Locations (1)
Warren Conference Center and Inn
🇺🇸Ashland, Massachusetts, United States