Clinical trial NCT00315354: Popular Diets Study
Official title: Popular Diets, Metabolism, and CVD Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Insulin Resistance
Keywords: obesity
nutrition
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Brigham and Women's Hospital
First posted: 2006-04-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The aim of this study is to evaluate the effects of three dominant dietary patterns - conventional low-fat, low-glycemic index (GI) and very-low-carbohydrate - on energy metabolism and heart disease risk factors following weight loss in obese young adults in a feeding study

Detailed description: For most of the last half century, reduction in fat intake has been the primary nutritional approach for the prevention and treatment of obesity and cardiovascular disease (CVD). Over the last few years, very low carbohydrate (Atkins-type) diets have achieved great popularity, with publication of several studies suggesting greater weight loss and improvements in CVD risk factors over 3 to 6 months. Recently, a third dietary approach focused on glycemic index (GI) has generated interest. However, few studies have compared the effects of these diets on body weight regulation and risk for CVD. The primary hypotheses of this study are that any diet that lowers the postprandial rise in blood glucose (very-low-carbohydrate or low-GI) will have beneficial effects on the physiological adaptations to weight loss and on some CVD risk factors. However, other CVD risk factors will be adversely affected by a very-low-carbohydrate vs. a low-GI diet. Preliminary data provide strong support for these hypotheses, by showing that resting energy expenditure declines less and CVD risk factors improve more with weight loss on a low-glycemic load diet compared to a conventional low-fat diet. This application proposes a cross-over feeding design to study the effects of three diets following 12.5% weight loss in obese young adult subjects (n = 24, age 18 to 40 years). The diets are: 1) conventional low-fat, with 60% carb, 20% fat, 20% protein; 2) low-GI with 40% carb, 40% fat, 20% protein; and 3) very-low-carbohydrate with 10% carb, 60% fat, 30% protein. The primary outcome is resting energy expenditure (indirect calorimetry). Secondary outcomes include total energy expenditure (doubly labeled water), thermic effect of food (indirect calorimetry), physical activity (accelerometry), insulin resistance and B-cell function (frequently-sampled OGTT), blood lipids, blood pressure and measures of systemic inflammation and coagulopathy. This study should have major public health implications to the millions of Americans currently following diets to decrease body weight and risk for heart disease.

Eligibility criteria: Inclusion Criteria:

* BMI ≥ 27 kg/m2
* Willing and able to come to the GCRC 5 days per week to consume a supervised meal and pick-up food for all other meals
* Available for scheduled hospital admissions
* Willing to abstain from alcohol consumption for the duration of the study
* If female, regular menstrual cycles (defined as 26 to 30 days between cycles; no more than one day variation in the duration of menstrual flow)

Exclusion Criteria:

* Weight \> 350 lbs
* Change in body weight (± 10%) over preceding year
* Taking any medications or dietary supplements that might affect body weight, appetite, or energy expenditure
* Smoking (1 cigarette in the last week)
* High levels of physical activity
* Currently following a special diet
* Abnormal laboratory screening tests
* Type 2 diabetes mellitus
* Allergies or aversions to foods on the study menu
* Previous diagnosis of an eating disorder or any other mental health disorder
* If female, pregnant in the past 12 months or planning to become pregnant during the study period
* If female, lactating in the preceding 12 months
* If taking birth control medication, change in medication in previous 3 months or plans to change medication during the study period

Primary outcomes:
measure: resting energy expenditure using indirect calorimetry in the fasting state
timeFrame: end of each dietary period
measure: insulin resistance assessed by frequently-sampled oral glucose tolerance test
timeFrame: end of each dietary period
measure: thyroid function tests
timeFrame: end of each dietary period
Secondary outcomes:
measure: total energy expenditure using doubly labeled water methodology
timeFrame: end of each dietary period
measure: thermic effect of food using indirect calorimetry
timeFrame: end of each dietary period
measure: physical activity using accelerometry
timeFrame: end of each dietary period
measure: serum lipids
timeFrame: end of each dietary period
measure: plasminogen activator inhibitor-1
timeFrame: end of each dietary period
measure: C-reactive protein
timeFrame: end of each dietary period
measure: blood pressure
timeFrame: end of each dietary period
measure: hunger/appetite
timeFrame: end of each dietary period
measure: insulin 30 minutes after oral glucose (as an effect modifier)
timeFrame: baseline
measure: Core temperature
timeFrame: End of each dietary period
measure: secreted frizzle-related protein-4
timeFrame: end of each dietary period
measure: heme-oxygenase
timeFrame: end of each dietary period
measure: Irisin
timeFrame: end of each dietary period
measure: fibroblast growth factor-21
timeFrame: end of each dietary period
measure: chemerin
timeFrame: end of each dietary period
measure: trimethylamine N-oxide
timeFrame: fasting and postprandial, end of each dietary period
measure: alanine aminotransferase
timeFrame: end of each dietary period
measure: Uric acid
timeFrame: end of each dietary period
measure: insulin
timeFrame: fasting and postprandial, end of each dietary period
measure: ghrelin
timeFrame: fasting and postprandial, end of each dietary period
measure: gastric inhibitory peptide
timeFrame: fasting and postprandial, end of each dietary period
measure: GLP1
timeFrame: fasting and postprandial, end of each dietary period
measure: PYY
timeFrame: fasting and postprandial, end of each dietary period
measure: Amylin
timeFrame: fasting and postprandial, end of each dietary period
measure: Leptin
timeFrame: end of each dietary period
measure: Metabolomic analysis
timeFrame: end of each dietary period
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
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: STUDY_DIRECTOR
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.
citation: Hron BM, Ebbeling CB, Feldman HA, Ludwig DS. Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism. Nutr Metab (Lond). 2017 Jul 5;14:44. doi: 10.1186/s12986-017-0198-y. eCollection 2017.
citation: Esko T, Hirschhorn JN, Feldman HA, Hsu YH, Deik AA, Clish CB, Ebbeling CB, Ludwig DS. Metabolomic profiles as reliable biomarkers of dietary composition. Am J Clin Nutr. 2017 Mar;105(3):547-554. doi: 10.3945/ajcn.116.144428. Epub 2017 Jan 11.