Framingham State Food Study

Study Overview
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Brief Summary
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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
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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).

Official Title
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Dietary Composition and Energy Expenditure During Weight-Loss Maintenance

Conditions
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Obesity, Diabetes, Cardiovascular Disease

Intervention / Treatment
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* Behavioral: Feeding study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low carbohydrate diet<br>Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein | Behavioral: Feeding study<br>* Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum<br>|
| Experimental: Moderate carbohydrate diet<br>Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein | Behavioral: Feeding study<br>* Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum<br>|
| Active Comparator: High carbohydrate diet<br>Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein | Behavioral: Feeding study<br>* Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| 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) | 
| 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 | 
| 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) | 
| 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 | 
| 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 | 
| 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) | 
| 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 | 
| Fibrinogen | Change: end of test phase - start of trial | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| 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) | 
| Thyroxine (T4) | thyroid function test | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| Free T4 | free thyroxine, thyroid function test | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Luteinizing Hormone |  | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| Follicle Stimulating Hormone |  | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| Body Weight Change During ad Libitum Feeding |  | Ad libitum feeding period (weeks 21 and 22 following randomization) | 
| Gut Microbiome Profile |  | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| Serum Metabolomics Profile |  | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| 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 | 
| 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 | 
| 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 | Beck Depression Inventory-II [BDI-II] | Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low carbohydrate diet, Low fat diet, Glycemic index, Weight loss maintenance