Clinical trial NCT02068885: Framingham State Food Study
Official title: Dietary Composition and Energy Expenditure During Weight-Loss Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Diabetes
Cardiovascular Disease
Keywords: Low carbohydrate diet
Low fat diet
Glycemic index
Weight loss maintenance
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Framingham State University
name: Baylor College of Medicine
name: Nutrition Science Initiative
name: New Balance Foundation
name: Many Voices Foundation
name: Blue Cross Blue Shield
First posted: 2014-02-21
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes
timeFrame: Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Secondary outcomes:
measure: Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Physical Activity, Assessed by Accelerometry
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Skeletal Muscle Work Efficiency
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Leptin (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: Leptin (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: Ghrelin (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: Ghrelin (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: 1,5-Anhydroglucitol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Glycemic Control, Assessed by HgA1c
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Triglycerides
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Body Composition (DXA)
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Glucose
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Lipoprotein Particle Subfraction Distribution
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Total Cholesterol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: HDL-Cholesterol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Non-HDL-Cholesterol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: LDL-Cholesterol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Adiponectin (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: Adiponectin (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: C-reactive Protein (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: C-reactive Protein (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: IL-6 (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: IL-6 (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: Blood Pressure
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Plasminogen Activator Inhibitor-1 (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: Plasminogen Activator Inhibitor-1 (% Change)
timeFrame: Change through 20 weeks' weight loss maintenance
measure: Fibrinogen
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial)
timeFrame: Start of trial (time of randomization, post-weight loss)
measure: Thyroxine (T4)
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Free T4
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Thyroid Stimulating Hormone
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Reverse T3
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Urinary Cortisol Excretion
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Urinary Catecholamine - Adrenaline
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Urinary Catecholamine - Dopamine
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Urinary Catecholamine - Noradrenaline
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Insulin Sensitivity (Hepatic), Assessed by Frequently-sampled Oral Glucose Tolerance Test
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Insulin Sensitivity (Systemic), Assessed by Frequently-sampled Oral Glucose Tolerance Test
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Non-esterified Fatty Acids
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Serum Ketones/Ketoacids
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Lactate
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Metabolic Fuel Concentration in Serum (Glucose, Nonesterified Fatty Acids, Ketones/Ketoacids, Lactate)
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Insulin-like Growth Factor 1 (IGF-1)
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: IGF Binding Proteins
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Testosterone
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Estradiol
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Luteinizing Hormone
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Follicle Stimulating Hormone
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Body Weight Change During ad Libitum Feeding
timeFrame: Ad libitum feeding period (weeks 21 and 22 following randomization)
measure: Gut Microbiome Profile
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Serum Metabolomics Profile
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Cognitive Function Related to Memory
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Cognitive Function Related to Processing Speed and Executive Function
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Sleep Quality
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Depression Measure
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Mood/Anxiety
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Food Addiction Score
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Emotional Eating Score
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Change in Self-reported Binge Eating Score
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Other outcomes:
measure: Effect Modification by Insulin Secretion of Metabolic Responses to Diet
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Effect Modification by Insulin Resistance of Metabolic Responses to Diet
timeFrame: Start of (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
measure: Effect Modification by Amylase Gene Copy Number
timeFrame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Locations:
city: Framingham
country: United States
facility: Framingham State University
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Gloria Klein, MS, RD
role: STUDY_DIRECTOR
affiliation: Boston Children's Hospital
name: Cara B Ebbeling, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: David S Ludwig, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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/bmj.k4583.
citation: 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: 10.1093/jn/nxaa150.
citation: Wong JMW, Yu S, Ma C, Mehta T, Dickinson SL, Allison DB, Heymsfield SB, Ebbeling CB, Ludwig DS. Stimulated Insulin Secretion Predicts Changes in Body Composition Following Weight Loss in Adults with High BMI. J Nutr. 2022 Mar 3;152(3):655-662. doi: 10.1093/jn/nxab315.
citation: Ebbeling CB, Knapp A, Johnson A, Wong JMW, Greco KF, Ma C, Mora S, Ludwig DS. Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia-a randomized controlled feeding trial. Am J Clin Nutr. 2022 Jan 11;115(1):154-162. doi: 10.1093/ajcn/nqab287.