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FB4 (Framingham, Boston, Bloomington, Birmingham, and Baylor)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03394664
Recruitment Status : Suspended (In light of COVID-19, the FB4 trial is indefinitely on hold.)
First Posted : January 9, 2018
Last Update Posted : May 18, 2020
Sponsor:
Collaborators:
Indiana University
University of Alabama at Birmingham
Framingham State University
Baylor University
Information provided by (Responsible Party):
David S. Ludwig, MD, PhD, Boston Children’s Hospital

Tracking Information
First Submitted Date  ICMJE December 29, 2017
First Posted Date  ICMJE January 9, 2018
Last Update Posted Date May 18, 2020
Actual Study Start Date  ICMJE January 29, 2018
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
Body fat mass [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
Body composition assessed using a multi-component model
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2019)
  • Lean body mass [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Hemoglobin A1c [HbA1c]
  • Total cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • HDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • LDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • Non-HDL cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • Triglycerides [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Indicator of chronic inflammation
  • Uric acid [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Assessed by auscultation, mmHg
  • Diastolic blood pressure [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Assessed by auscultation, mmHg
  • Thyroxine (T4) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function
  • Free T4 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function
  • Thyroid stimulating hormone [TSH] [ Time Frame: 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] [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Growth hormone action
  • Urine cortisol [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • Total Adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • High-molecular weight adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • Sleep [ Time Frame: 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 [ Time Frame: Measurements made daily during residential phase (0 to 10 weeks) and integrated into a unified outcome ]
    Assessed by continuous glucose monitoring (CGM)
  • Ghrelin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Hormonal Control of Appetite
  • Body Circumference [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Lean body mass [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Measurements made daily during residential phase (0 to 10 weeks) and integrated into a unified outcome ]
    Total minutes of moderate- to vigorous-intensity physical activity, assessed by accelerometry
  • Insulin sensitivity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Hemoglobin A1c [HbA1c]
  • Total cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • HDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • LDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • Non-HDL cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor
  • Triglycerides [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Indicator of chronic inflammation
  • Uric acid [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Assessed by auscultation, mmHg
  • Diastolic blood pressure [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Assessed by auscultation, mmHg
  • Thyroxine (T4) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function
  • Free T4 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function
  • Thyroid stimulating hormone [TSH] [ Time Frame: 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] [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Growth hormone action
  • Urine cortisol [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • Total Adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • High-molecular weight adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine
  • Sleep [ Time Frame: Measurements made daily during residential phase (0 to 10 weeks) and integrated into a unified outcome ]
    Total sleep time, sleep onset latency, wake after sleep onset, and sleep efficiency, assessed by accelerometry
  • Blood glucose [ Time Frame: Measurements made daily during residential phase (0 to 10 weeks) and integrated into a unified outcome ]
    Assessed by continuous glucose monitoring (CGM)
Current Other Pre-specified Outcome Measures
 (submitted: April 30, 2019)
  • 1,5-anhydroglucitol (1,5-AG) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Lipoprotein particle subfraction distribution [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Fibrinogen [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Estradiol (E2) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Metabolomics profile [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • MicroRNA [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Gut microbiome [ Time Frame: 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) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Body composition (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (insulin-30) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (glycemic control) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Obesity related genetic risk (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Body composition (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (insulin-30) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (glycemic control) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Physical activity level (moderate to vigorous) (mediator/modifier) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analysis of archived specimen
  • Urinary nitrogen [ Time Frame: End of residential (END, 10 weeks) ]
    Archived for future analysis
  • Glucagon-like peptide-1 (GLP-1) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived samples
  • Glucagon [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived samples
  • Oxytocin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived samples
  • Oxyntomodulin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived samples
Original Other Pre-specified Outcome Measures
 (submitted: January 3, 2018)
  • Urine c-peptide [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Lipoprotein particle subfraction distribution [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Fibrinogen [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Estradiol (E2) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Ghrelin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analysis of archived specimen
  • Metabolomics profile [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • MicroRNA [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Possible future analyses of archived specimen
  • Gut microbiome [ Time Frame: 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) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Habitual diet (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Body composition (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (insulin-30) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Measure of glucose homeostasis (glycemic control) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Obesity related genetic risk (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate
  • Body composition (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (insulin-30) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Measure of glucose homeostasis (glycemic control) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
  • Physical activity (minutes of moderate to vigorous) (mediator/modifier) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Time varying covariate
 
Descriptive Information
Brief Title  ICMJE FB4 (Framingham, Boston, Bloomington, Birmingham, and Baylor)
Official Title  ICMJE Macronutrients and Body Fat Accumulation: A Mechanistic Feeding Study
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Obesity
Intervention  ICMJE Behavioral: Feeding Study
Food provision throughout the study: 1) Run-In Phase (VLC diet, weight loss); 2) Residential Phase (3 different test diets, weight-loss maintenance).
Other Name: weight loss, weight-loss maintenance
Study Arms  ICMJE
  • Experimental: Very-Low Carbohydrate Diet
    Feeding study. Dietary composition (approximately): 75% fat
    Intervention: Behavioral: Feeding Study
  • Experimental: High-Carbohydrate Low-Sugar Diet
    Feeding study. Dietary composition (approximately): 25% fat 0% added sugars.
    Intervention: Behavioral: Feeding Study
  • Experimental: High-Carbohydrate High-Sugar Diet
    Feeding study. Dietary composition (approximately): 25% fat, 20% added sugars.
    Intervention: Behavioral: Feeding Study
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: January 3, 2018)
125
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03394664
Other Study ID Numbers  ICMJE IRB-P00026977
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David S. Ludwig, MD, PhD, Boston Children’s Hospital
Study Sponsor  ICMJE Boston Children’s Hospital
Collaborators  ICMJE
  • Indiana University
  • University of Alabama at Birmingham
  • Framingham State University
  • Baylor University
Investigators  ICMJE
Principal Investigator: David S Ludwig, MD, PhD Boston Children’s Hospital
Principal Investigator: David B Allison, PhD Indiana University Bloomington
Study Director: Cara B Ebbeling, PhD Boston Children’s Hospital
PRS Account Boston Children’s Hospital
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP