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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 : Terminated (The FB4 trial has been terminated due to COVID-19.)
First Posted : January 9, 2018
Last Update Posted : October 20, 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

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.

Condition or disease Intervention/treatment Phase
Obesity Behavioral: Feeding Study Not Applicable

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Primary Purpose: Treatment
Official Title: Macronutrients and Body Fat Accumulation: A Mechanistic Feeding Study
Actual Study Start Date : January 29, 2018
Actual Primary Completion Date : May 3, 2020
Actual Study Completion Date : May 3, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Weight Control

Arm Intervention/treatment
Experimental: Very-Low Carbohydrate Diet
Feeding study. Dietary composition (approximately): 75% fat
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

Experimental: High-Carbohydrate Low-Sugar Diet
Feeding study. Dietary composition (approximately): 25% fat 0% added sugars.
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

Experimental: High-Carbohydrate High-Sugar Diet
Feeding study. Dietary composition (approximately): 25% fat, 20% added sugars.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Glycemic control [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Hemoglobin A1c [HbA1c]

  9. Total cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor

  10. HDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor

  11. LDL-cholesterol [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor

  12. 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

  13. Triglycerides [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Chronic disease risk factor

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Thyroxine (T4) [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function

  20. Free T4 [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function

  21. Thyroid stimulating hormone [TSH] [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Thyroid function

  22. 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

  23. 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

  24. 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

  25. Leptin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine

  26. Total Adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine

  27. High-molecular weight adiponectin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Adipokine

  28. 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

  29. 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)

  30. Ghrelin [ Time Frame: Change from post-weight loss (PWL, 0 weeks) to end of residential study (END, 10 weeks) ]
    Hormonal Control of Appetite

  31. 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

  32. 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

  33. 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


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Demographics (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  18. Body composition (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  19. Measure of glucose homeostasis (insulin-30) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  20. Measure of glucose homeostasis (insulin sensitivity) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  21. Measure of glucose homeostasis (glycemic control) (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  22. Obesity related genetic risk (mediator/modifier) [ Time Frame: Pre-weight loss baseline ]
    Baseline covariate

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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.

  28. 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

  29. Urinary nitrogen [ Time Frame: End of residential (END, 10 weeks) ]
    Archived for future analysis

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03394664


Locations
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United States, Massachusetts
Warren Conference Center and Inn
Ashland, Massachusetts, United States, 01721
Sponsors and Collaborators
Boston Children's Hospital
Indiana University
University of Alabama at Birmingham
Framingham State University
Baylor University
Investigators
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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
Publications:
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Responsible Party: David S. Ludwig, MD, PhD, Co-Director, New Balance Foundation Obesity Prevention Center, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT03394664    
Other Study ID Numbers: IRB-P00026977
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by David S. Ludwig, MD, PhD, Boston Children's Hospital:
Body composition
Feeding study
Ketogenic diet
Weight loss
Energy Expenditure