Framingham State Food Study

Obesity Clinical Trial

— (FS)2  

Official title:

Dietary Composition and Energy Expenditure During Weight-Loss Maintenance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02068885
• Other study ID #: IRB-P00009571
• Status: Completed
• Phase: N/A
• Start date: August 17, 2014
• Est. completion date: May 2017

Study information

• Verified date: March 2022
• Source: Boston Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the effects of dietary composition on energy expenditure and chronic disease risk factors, while also exploring physiological mechanisms underlying these effects.

Description:

Many overweight and obese people can lose weight for a few months, but most have difficulty maintaining weight loss over the long term. One explanation for the poor long-term outcome of weight-loss diets relates to behavior, in that motivation to adhere to restrictive regimens typically diminishes with time. An alternative explanation is that weight loss elicits biological adaptations - specifically a decline in energy expenditure and an increase in hunger - that promote weight regain. The purpose of this study is to evaluate the effects of dietary composition on energy expenditure and risk for chronic diseases, while also exploring physiological mechanisms underlying these effects. The study will be performed in collaboration with Framingham State University, providing a novel and feasible method for feeding subjects in dining halls and monitoring compliance.

Following 12±2% weight loss on a standard run-in diet, 150 adults (aged 18 to 65 years) will be randomly assigned to one of three weight-loss maintenance diets controlled for protein content (20% of energy) and varying widely in dietary carbohydrate-to-fat ratio: Low-carbohydrate (20% of energy from carbohydrate, 60% fat), Moderate- carbohydrate (40% carbohydrate, 40% fat), High-carbohydrate (60% carbohydrate, 20% fat). During the weight-loss maintenance phase, energy intake will be adjusted to prevent changes in body weight. The primary outcome will be change in total energy expenditure (indirect calorimetry using stable isotopes) through 20 weeks. Secondary outcomes during weight maintenance will include resting energy expenditure (indirect calorimetry using respiratory gas exchange), physical activity (accelerometry), measures of insulin resistance and skeletal muscle work efficiency, components of the metabolic syndrome, and hormonal and metabolic measures that might inform an understanding of physiological mechanisms. We also will assess weight change during a 2-week ad libitum feeding phase, as an objective measure of dietary effects on hunger. The analytic framework for addressing study hypothesis will be repeated-measures analysis of variance, with adjustment for covariates (sex, race, ethnicity, age, anthropometrics, insulin sensitivity and secretion, obesity-related genes). We also will test each covariate for effect modification (covariate × diet interaction).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 234
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged 18 to 65 years

• BMI = 25 kg/m2

• Weight = 425 lbs

• Medical clearance from a primary care provider

• Plans to matriculate at Framingham State University (campus-based participants:

students), work on campus (campus-based participants: faculty and staff), or live in the greater Framingham area (community-based participants) throughout the academic year of enrollment in the study

• Academic and social clearance from the FSU Office of Enrollment and Student Development (student participants) or willingness to comply with Criminal Offender Record Information (CORI) check and Sex Offender Registry Information (SORI) check (community-based subjects)

• Willingness to eat and drink only the foods and beverages on the study menus during participation, with no food allergies or aversions

• Willingness to eat in the dining hall

• Willingness to abstain from consuming alcohol during participation

Exclusion Criteria:

• Change in body weight exceeding ±10% during prior year

• Recent adherence to a special diet

• Recent adherence to a vigorous physical activity regimen (e.g., participation in a varsity sport)

• Chronic use of any medication or dietary supplement that could affect study outcomes

• Current smoking (1 cigarette in the last week)

• Heavy baseline alcohol consumption (> 10 drinks/week) or history of binge drinking (= 5 drinks in 1 day, anytime in past 6 months)

• Physician diagnosis of a major medical/psychiatric illness or eating disorder

• Abnormal HgA1c, TSH, BUN, creatinine; hematocrit < 30; ALT > 200% of normal upper limit

• Plans for a vacation during the study that would preclude adherence to prescribed diet

• Additional exclusions for female participants: Irregular menstrual cycles; any change in birth control medication during the 3 months prior to enrollment; pregnancy or lactation during the 12 months prior to enrollment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes
• Obesity

Intervention

Behavioral:
• Feeding study
Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum

Locations

Country	Name	City	State
United States	Framingham State University	Framingham	Massachusetts

Sponsors (7)

Lead Sponsor	Collaborator
Boston Children's Hospital	Baylor College of Medicine, Blue Cross Blue Shield, Framingham State University, Many Voices Foundation, New Balance Foundation, Nutrition Science Initiative

Country where clinical trial is conducted

United States, 

References & Publications (5)

Ebbeling CB, Bielak L, Lakin PR, Klein GL, Wong JMW, Luoto PK, Wong WW, Ludwig DS. Energy Requirement Is Higher During Weight-Loss Maintenance in Adults Consuming a Low- Compared with High-Carbohydrate Diet. J Nutr. 2020 Aug 1;150(8):2009-2015. doi: 10.10 — View Citation

Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, Wong WW, Ludwig DS. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018 Nov 14;363:k4583. doi: 10.1136/b — View Citation

Ebbeling CB, Klein GL, Luoto PK, Wong JMW, Bielak L, Eddy RG, Steltz SK, Devlin C, Sandman M, Hron B, Shimy K, Heymsfield SB, Wolfe RR, Wong WW, Feldman HA, Ludwig DS. A randomized study of dietary composition during weight-loss maintenance: Rationale, study design, intervention, and assessment. Contemp Clin Trials. 2018 Feb;65:76-86. doi: 10.1016/j.cct.2017.12.004. Epub 2017 Dec 9. — View Citation

Ludwig DS, Greco KF, Ma C, Ebbeling CB. Testing the carbohydrate-insulin model of obesity in a 5-month feeding study: the perils of post-hoc participant exclusions. Eur J Clin Nutr. 2020 Jul;74(7):1109-1112. doi: 10.1038/s41430-020-0658-8. Epub 2020 May 20. — View Citation

Wong JM, Bielak L, Eddy RG, Stone L, Lakin PR, Sandman M, Devlin C, Seger-Shippee L, Wiroll D, Luoto PK, Klein GL, Ludwig DS, Ebbeling CB. An Academia-Industry Partnership for Planning and Executing a Community-Based Feeding Study. Curr Dev Nutr. 2018 Jul 5;2(9):nzy060. doi: 10.1093/cdn/nzy060. eCollection 2018 Sep. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect Modification by Insulin Secretion of Metabolic Responses to Diet	Effect modifier: Insulin level 30 minutes into an standard OGTT (Insulin-30) Outcome: Total Energy Expenditure Tertiles: Pre-weight-loss Insulin-30 (Low, Moderate, High) Change: average (midpoint of test phase, end of test phase) - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Other	Effect Modification by Insulin Resistance of Metabolic Responses to Diet		Start of (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Other	Effect Modification by Amylase Gene Copy Number		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Primary	Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes	Total energy expenditure (TEE), assessed by indirect calorimetry using stable isotopes; Total calories burned: Participants each drank about a cup of water containing special tracers which are measurable when they pass out of the body through urine. They provided a urine sample before they drank the water and then about every other day for the next two (2) weeks.; Change: average (midpoint of test phase, end of test phase) - start of trial	Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange	Resting energy expenditure, assessed by indirect calorimetry using respiratory gas exchange Calories burned while resting: Participants lied down with head and neck under a clear plastic "bubble," breathing room air. Gases in expired air were collected.; Change: average (midpoint of test phase, end of test phase) - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Physical Activity, Assessed by Accelerometry	Actigraph Accelerometer Change: average (midpoint of test phase, end of test phase) - start of trial An Actigraph Accelerometer measures movement, similar to a pedometer. Data are reported as counts (divided by 1,000) per day. Each participant wore the the accelerometer on the right hip for 7 days at each time point.	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Skeletal Muscle Work Efficiency	Efficiency is expressed as percentage ratio of power generated during cycle ergometry (with conversion of Watts to kcal/min using a factor of 0.01433) to energy expenditure above resting.; Change: end of test phase - start of trial.	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Leptin (Start of Trial)	Leptin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 6) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	Leptin (% Change)	Leptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	Ghrelin (Start of Trial)	Ghrelin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 8) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	Ghrelin (% Change)	Ghrelin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	1,5-Anhydroglucitol	Biomeasure of carbohydrate intake Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Glycemic Control, Assessed by HgA1c	Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Triglycerides	Triglyceride levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Body Composition (DXA)	Body fat, presented as a % of total mass; Participants each had a special scan (x-ray) to measure their amount of body fat. The special x-ray is called "dual-energy x-ray absorptiometry" (DXA). They were asked to lie still on a table for x-ray pictures.; Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Glucose	Glucose level, fasting blood draw Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Lipoprotein Particle Subfraction Distribution	Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). LPIR score is quantified on a scale of 0-100. Higher scores indicate worse outcome.; Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Total Cholesterol	Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	HDL-Cholesterol	High-density lipoprotein cholesterol Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Non-HDL-Cholesterol	Calculated by subtracting HDL-cholesterol from total cholesterol. Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	LDL-Cholesterol	Low-density-lipoprotein cholesterol Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Adiponectin (Start of Trial)	Total and high molecular weight adiponectin Adiponectin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 20) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	Adiponectin (% Change)	Adiponeptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	C-reactive Protein (Start of Trial)	C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 22) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	C-reactive Protein (% Change)	C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	IL-6 (Start of Trial)	Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 24) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	IL-6 (% Change)	Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	Blood Pressure	Systolic and diastolic blood pressure Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Plasminogen Activator Inhibitor-1 (Start of Trial)	Plasminogen activator inhibitor-1 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)).; Changes (see Outcome 27) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial	Start of trial (time of randomization, post-weight loss)
Secondary	Plasminogen Activator Inhibitor-1 (% Change)	Plasminogen activator inhibitor-1 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial	Change through 20 weeks' weight loss maintenance
Secondary	Fibrinogen	Change: end of test phase - start of trial	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial)	Insulin level 30 minutes after consuming 75 grams of glucose	Start of trial (time of randomization, post-weight loss)
Secondary	Thyroxine (T4)	thyroid function test	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Free T4	free thyroxine, thyroid function test	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Thyroid Stimulating Hormone	Produced by the pituitary gland in the brain. Tells the thyroid gland to make thyroid hormones.	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Reverse T3	thyroid function test, inactive form of triiodothyronine (T3) Lifespan Bio kit was used for analysis. The range of this kit is 250 to 5000 pg/mL, which varies from other commercially available kits (about 10-fold greater values).	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Urinary Cortisol Excretion	cortisol (stress hormone) excreted in the urine over a 24-hour period	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Urinary Catecholamine - Adrenaline	catecholamine excreted in the urine over 24 hours, also known as epinephrine	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Urinary Catecholamine - Dopamine	catecholamine excreted in the urine over 24 hours	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Urinary Catecholamine - Noradrenaline	catecholamine excreted in the urine over 24 hours, also known as norepinephrine	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Insulin Sensitivity (Hepatic), Assessed by Frequently-sampled Oral Glucose Tolerance Test		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Insulin Sensitivity (Systemic), Assessed by Frequently-sampled Oral Glucose Tolerance Test		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Non-esterified Fatty Acids		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Serum Ketones/Ketoacids		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Lactate		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Metabolic Fuel Concentration in Serum (Glucose, Nonesterified Fatty Acids, Ketones/Ketoacids, Lactate)		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Insulin-like Growth Factor 1 (IGF-1)		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	IGF Binding Proteins		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Testosterone		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Estradiol		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Luteinizing Hormone		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Follicle Stimulating Hormone		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Body Weight Change During ad Libitum Feeding		Ad libitum feeding period (weeks 21 and 22 following randomization)
Secondary	Gut Microbiome Profile		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Serum Metabolomics Profile		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Cognitive Function Related to Memory	California Verbal Learning Test - Second Edition [CVLT-II] and Digit Span Test	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Cognitive Function Related to Processing Speed and Executive Function	Trail Making Test Parts A and B [TMT-A, TMT-B]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Sleep Quality		Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Depression Measure	Beck Depression Inventory-II [BDI-II]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Mood/Anxiety	Mood and Anxiety Symptom Questionnaire [MASQ]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Food Addiction Score	Yale Food Addiction Scale [YFAS]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Emotional Eating Score	Emotional Eating Scale [EES]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary	Change in Self-reported Binge Eating Score	Binge Eating Scale [BES]	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance