Clinical trial NCT02235038: Metabolic Fuels Study
Official title: A Mechanistic Examination of Dietary Composition on Metabolic Fuels Availability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Framingham State University
name: Brigham and Women's Hospital
name: Boston Medical Center
name: Nutrition Science Initiative
name: New Balance Foundation
First posted: 2014-09-09
Enrollment: 30
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: BASIC_SCIENCE

Brief summary: This study will evaluate a potential physiologic mechanism underlying the effects of dietary composition on control of body weight

Detailed description: The challenge in maintaining long-term weight loss is well known, however new research suggests diet quality may be the driving factor. A pilot study from our group demonstrated that a higher carbohydrate-containing diet was associated with lower total energy expenditure during weight loss maintenance (Ebbeling et al). These findings will be confirmed in the ongoing Framingham State Food Study (NCT02068885): Following weight loss on a standard diet, 150 overweight or obese adults (aged 18 to 65 years) will be randomized to one of three weight-loss maintenance diets varying in carbohydrate to fat ratios for 20 weeks.

However, the specific mechanisms underlying the calorie-independent effects of diet remain unclear. Another study from our group demonstrated lower energy availability (calculated based on caloric content of circulating metabolic fuel concentrations) in the fasting and late post-prandial periods in 8 overweight or obese young adults who were maintained on a low-fat (high-carbohydrate) diet (Walsh et al). We hypothesize that this lower metabolic fuel availability on a high carbohydrate diet results in part from increased anabolic changes within the adipocyte, favoring fat storage in preference to oxidation.

We will invite subjects already enrolled in the Framingham State Food Study to participate, aiming for a total of 30 subjects (with the goal of approximately equal numbers per diet group following randomization to assigned test diet in the parent study). Participants will be admitted to a research unit for a 24-hour period during weight maintenance on the test diet, during which they will undergo frequent blood sampling for the measurement of circulating metabolic fuels, hunger and satiety ratings, while consuming their assigned diet meals. Each participant will also undergo two abdominal subcutaneous fat aspiration biopsies under local anesthesia, the first immediately following weight loss (before initiating the test diet) and the second during weight maintenance, in order to perform gene expression analyses on the adipose tissue. Our main outcomes will be a comparison in energy availability (the sum of energy in the major metabolic fuels in the blood) between diet groups in the late postprandial period and changes in adipose tissue gene expression within-individuals and by diet group assignment. Other outcomes will include differences in hunger and satiety ratings, total 24-hour energy availability, and specific metabolic fuel concentrations.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria (as detailed in Framingham State Food Study, NCT02068885)

* Aged 18 to 65 years
* BMI ≥ 25 kg/m2
* BMI \< 40 kg/m2 and weight ≤ 300 lbs (136 kg)
* Medical clearance from a primary care provider
* Student or employee at Framingham State University throughout enrollment in the study
* Willing and able to eat and drink only the foods and beverages on the study menus
* Willing to eat in the dining hall
* Willing to abstain from consuming alcohol during participation

Additional Inclusion Criteria:

• Willing to undergo additional procedures in this ancillary study

Exclusion Criteria:

Exclusion Criteria (as detailed in Framingham State Food Study, NCT02068885)

* 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 or history of binge drinking
* Physician diagnosis of a major medical/psychiatric illness or eating disorder
* Abnormal blood glucose, TSH, CBC, BUN, Creatinine
* ALT greater than 150% of the 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

Additional Exclusion Criteria:

* Allergy or prior reaction to Lidocaine
* Medical condition or medication that would increase risk of bleeding, infection or skin reactions

Primary outcomes:
measure: Late postprandial energy availability
timeFrame: 10 - 15 weeks after initiation of test diets
Secondary outcomes:
measure: Late postprandial energy availability, with lactate excluded
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Fasting energy availability
timeFrame: 10 - 15 weeks after initiation of test diet
measure: Total energy availability
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Hunger
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Satiety
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Glucose
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Non-esterified fatty acids
timeFrame: 10 - 15 weeks after initiation after test diet
measure: Lactate
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Ketoacids
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Insulin
timeFrame: 10 - 15 weeks after initiation of test diets
Other outcomes:
measure: Effect modification by insulin secretion
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Adipocyte studies of anabolic status
timeFrame: 10 - 15 weeks after initiation of test diets
measure: Adipose tissue histology
timeFrame: 10 - 15 weeks after initiation of test diets
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Framingham
country: United States
facility: Framingham State University
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Kim Shams, MD
role: STUDY_DIRECTOR
affiliation: Boston Children's Hospital
name: David s Ludwig, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Cara B Ebbeling, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Walsh CO, Ebbeling CB, Swain JF, Markowitz RL, Feldman HA, Ludwig DS. Effects of diet composition on postprandial energy availability during weight loss maintenance. PLoS One. 2013;8(3):e58172. doi: 10.1371/journal.pone.0058172. Epub 2013 Mar 6.
citation: Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA. 2012 Jun 27;307(24):2627-34. doi: 10.1001/jama.2012.6607.