Reduced Carbohydrate Versus Fat in Obese Subjects
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 2

Summary: 
      Popular weight loss strategies often involve reducing an individual's consumption of
      carbohydrates or fat. However, no controlled study has been carried out to evaluate the
      effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at
      standard levels to maintain an individual's weight. Researchers are interested in
      investigating how different restrictions of carbohydrates or fats affect the many processes
      involved in weight loss, including brain activity and blood and brain chemical composition.
    

Detailed description: 
      Popular weight loss strategies often prescribe a targeted reduction of dietary carbohydrate
      or fat. But surprisingly, no controlled human feeding study has ever investigated the effects
      of a selective reduction of dietary carbohydrate versus fat while keeping the other dietary
      macronutrients at their baseline weight-maintenance values. The present study was designed to
      address this knowledge gap and improve our understanding of how selective reduction of
      dietary fat versus carbohydrate may differentially impact the many feedback control processes
      that act to resist weight loss.

      Objectives:

      - To determine the comparative effects of two controlled fat- or carbohydrate-restricted
      diets and an outpatient weight loss program on blood and brain chemical composition, weight
      loss (fat and lean body mass), and regional brain activity in lean and obese individuals.

      Eligibility:

      - Healthy individuals between 18 and 45 years of age who are either lean (body mass index
      between 18.5 kg/m(2) and 25 kg/m(2)) or obese (body mass index above 30.0 kg/m(2), weight
      less than 350 pounds) and are right-handed.

      Design:

        -  Lean participants: Participants will be screened with a medical history, physical
           examination, blood and urine tests, and weight maintenance observations (food diaries
           and physical activity monitors). For the scanning visit, participants will receive
           balanced meals from the National Institutes of Health to consume for 2 days before the
           visit. During the scanning visit, participants will continue to eat the weight
           maintenance diet, complete questionnaires, and have a series of imaging studies
           (including positron emission tomography and magnetic resonance imaging tests) to
           evaluate brain response to food and other stimuli.

        -  Obese participants: Participants will be screened with a medical history, physical
           examination, blood and urine tests, and weight maintenance observations (food diaries
           and physical activity monitors). During the first inpatient visit, obese participants
           will eat a weight-maintenance diet for 5 days to establish baseline measurements. After
           several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI above
           30 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5
           additional days of the baseline diet, their diets will be modified to result in either
           85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary
           carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric
           reduction. The primary outcome measurements will be changes of metabolism, brain reward
           circuitry and regional brain activity in response to food stimuli measured during the
           baseline and reduced calorie diet phases. Immediately following each controlled diet, we
           will measure 3 days of ad-libitum food intake using a computerized vending machine
           system. The subjects will return to the MCRU after a 2-10 week washout period to receive
           the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI
           between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional
           brain activity in response to food stimuli while on a balanced, weight-maintenance diet.
           Immediately following the second in-patient visit, all of the obese subjects will be
           assigned to a 12 week out-patient weight loss program with the goal of achieving at
           least 5% weight loss. We will investigate the relationship between short-term fat
           imbalances measured during the in-patient phases, and the body weight and fat changes
           during the weight loss program. We will evaluate the effects of weight loss on
           metabolism, brain reward circuitry, and regional brain activity in response to food
           stimuli. Finally, if the subjects are available for long-term follow-up, then we will
           investigate their metabolic phenotype, brain reward circuitry, and regional brain
           activity in response to food stimuli yearly over the subsequent 5 years following the
           weight loss intervention. This study will result in an improved understanding of the
           physiological mechanisms that sense and respond to negative energy balance acutely,
           after several weeks, and after several years, and may eventually lead to increased
           long-term success of obesity treatment.
    

Intervention name(s): Reduced fat diet; Reduced carbohydrate diet; Drug: f-18 fallypride; fMRI; PET
Intervention type(s): Other; Other; Drug; Device; Device
Intervention description(s): RF (selective reduction of 85% of baseline fat calories per day); RC (selective reduction of 60% of baseline carbohydrate calories per day); Dopamine D2 receptor availability is measured by positron emission tomography (PET) using the positron emitting compound [18F] fallypride which binds competitively with dopamine to the D2 receptor.; Functional MRI (fMRI) will be used to measure the effects of diet and weight loss on regional brain activity; Positron emission tomography (PET) will be used to assess whether To assess whether brain activity and reward pathways are altered
Other intervention name(s): Functional MRI; Positron emission tomography
Intervention MeSH terms: Fallypride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Weight Loss; Carbohydrate; Fat; Macronutrient Balance; Healthy Volunteer