Framingham State Food Study

Not Applicable

Completed

Conditions: Obesity
Diabetes
Cardiovascular Disease

Interventions: Behavioral: Feeding study

Registration Number: NCT02068885

Lead Sponsor: Boston Children's Hospital

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 234

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low carbohydrate diet	Feeding study	Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein
Moderate carbohydrate diet	Feeding study	Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein
High carbohydrate diet	Feeding study	Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein

Primary Outcome Measures

Name	Time	Method
Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes	Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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

Secondary Outcome Measures

Name	Time	Method
Serum Metabolomics Profile	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
C-reactive Protein (% Change)	Change through 20 weeks' weight loss maintenance	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
IL-6 (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
IL-6 (% Change)	Change through 20 weeks' weight loss maintenance	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
Thyroxine (T4)	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	thyroid function test
Free T4	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	free thyroxine, thyroid function test
Thyroid Stimulating Hormone	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Produced by the pituitary gland in the brain. Tells the thyroid gland to make thyroid hormones.
Reverse T3	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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).
Urinary Cortisol Excretion	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	cortisol (stress hormone) excreted in the urine over a 24-hour period
Urinary Catecholamine - Adrenaline	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	catecholamine excreted in the urine over 24 hours, also known as epinephrine
Urinary Catecholamine - Dopamine	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	catecholamine excreted in the urine over 24 hours
C-reactive Protein (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
Urinary Catecholamine - Noradrenaline	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	catecholamine excreted in the urine over 24 hours, also known as norepinephrine
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
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
Non-esterified Fatty Acids	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Serum Ketones/Ketoacids	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Lactate	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
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
Triglycerides	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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
Body Composition (DXA)	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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
Glucose	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Glucose level, fasting blood draw Change: end of test phase - start of trial
Change in Lipoprotein Particle Subfraction Distribution	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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
Total Cholesterol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Change: end of test phase - start of trial
Gut Microbiome Profile	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Blood Pressure	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Systolic and diastolic blood pressure Change: end of test phase - start of trial
Plasminogen Activator Inhibitor-1 (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
HDL-Cholesterol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	High-density lipoprotein cholesterol Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.
Non-HDL-Cholesterol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Calculated by subtracting HDL-cholesterol from total cholesterol. Change: end of test phase - start of trial
LDL-Cholesterol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Low-density-lipoprotein cholesterol Change: end of test phase - start of trial
Adiponectin (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
Adiponectin (% Change)	Change through 20 weeks' weight loss maintenance	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
Luteinizing Hormone	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Plasminogen Activator Inhibitor-1 (% Change)	Change through 20 weeks' weight loss maintenance	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
Fibrinogen	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Change: end of test phase - start of trial
Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial)	Start of trial (time of randomization, post-weight loss)	Insulin level 30 minutes after consuming 75 grams of glucose
Follicle Stimulating Hormone	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Leptin (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
Leptin (% Change)	Change through 20 weeks' weight loss maintenance	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
Ghrelin (Start of Trial)	Start of trial (time of randomization, post-weight loss)	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
Ghrelin (% Change)	Change through 20 weeks' weight loss maintenance	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
1,5-Anhydroglucitol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Biomeasure of carbohydrate intake Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial
Glycemic Control, Assessed by HgA1c	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.
Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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
Physical Activity, Assessed by Accelerometry	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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.
Skeletal Muscle Work Efficiency	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	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.
Body Weight Change During ad Libitum Feeding	Ad libitum feeding period (weeks 21 and 22 following randomization)
Insulin-like Growth Factor 1 (IGF-1)	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
IGF Binding Proteins	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Testosterone	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Estradiol	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Cognitive Function Related to Memory	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	California Verbal Learning Test - Second Edition \[CVLT-II\] and Digit Span Test
Change in Cognitive Function Related to Processing Speed and Executive Function	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Trail Making Test Parts A and B \[TMT-A, TMT-B\]
Change in Self-reported Sleep Quality	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Depression Measure	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Beck Depression Inventory-II \[BDI-II\]
Change in Self-reported Food Addiction Score	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Yale Food Addiction Scale \[YFAS\]
Change in Self-reported Emotional Eating Score	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Emotional Eating Scale \[EES\]
Change in Self-reported Binge Eating Score	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Binge Eating Scale \[BES\]
Change in Self-reported Mood/Anxiety	Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance	Mood and Anxiety Symptom Questionnaire \[MASQ\]