Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Macronutrient Diet on Brain Activity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02300857
Recruitment Status : Completed
First Posted : November 25, 2014
Last Update Posted : June 6, 2019
Sponsor:
Collaborators:
Boston Children’s Hospital
Nutrition Science Initiative
New Balance Foundation
Boston Medical Center
Framingham State University
Information provided by (Responsible Party):
Laura M. Holsen, Brigham and Women's Hospital

Brief Summary:
This study will evaluate the effect of macronutrient diets on brain activity in homeostatic and mesolimbic reward regions.

Condition or disease Intervention/treatment Phase
Obesity Behavioral: Low carbohydrate diet Behavioral: Moderate carbohydrate diet Behavioral: High carbohydrate diet Not Applicable

Detailed Description:

A question critical to the field of obesity is "what causes overweight and obese individuals to overeat?" One common explanation holds that weight gain at the population-level is caused by increases in the widespread availability of highly palatable foods. An alternative explanation is that the biological effects of the modern diet produce effects in the central nervous system and periphery that augment homeostatic and hedonic hunger. Reducing glycemic load preferentially maintains total energy expenditure during weight-loss maintenance (Ebbeling et al., 2012), and this group of investigators previously showed that in the late postprandial period, a nutrient-controlled high glycemic load vs. low glycemic load meal increases resting regional cerebral blood flow in the nucleus accumbens (Lennerz et al., 2013), part of the mesoaccumbal reward circuitry implicated in craving and addiction. However, the effects of macronutrient composition on blood flow to and activity in homeostatic and reward-related brain regions cannot be fully ascertained from studies of acute ingestion of a single macronutrient, because these do not generalize to mixed-nutrient meals consumed as part of typical American diets. Further, retrospective designs that rely on participant report of frequency of recent macronutrient ingestion and prospective designs with limited duration of diet prescription cannot address the critical question of the long-term, cumulative effects of dietary composition on brain function. Therefore, the investigators propose an approach to identifying brain responses to randomized, mixed-meal diets of varying macronutrient composition during long-term weight-loss maintenance on these diets, using arterial spin labeling (ASL) for regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD)-based functional connectivity.

To explore these outcomes, the investigators will partner with 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. Investigators will invite subjects already enrolled in the Framingham State Food Study to participate with a goal of enrolling 75 subjects (aiming to be equally divided per diet group following randomization to assigned test diet in the parent study). Participants will complete 1 morning visit to the MRI imaging center at Brigham and Women's Hospital approximately 14-20 weeks into the weight maintenance test diet phase. During the visit, they will undergo a fasting baseline brain imaging session, consume their assigned diet breakfast meal, and undergo a late postprandial brain imaging session. Participants will additionally provide frequent ratings of their food cravings, mood, and anxiety level throughout the visit. The main outcomes will be resting blood flow to the nucleus accumbens and connected striatal regions in the late postprandial period, with additional secondary and other outcomes including blood flow to the hypothalamus and connectivity between the hypothalamus during the late postprandial period.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Macronutrient Diet Composition on Brain Reward Activity
Actual Study Start Date : November 2014
Actual Primary Completion Date : April 30, 2017
Actual Study Completion Date : April 30, 2017

Arm Intervention/treatment
Active Comparator: Low carbohydrate diet Behavioral: Low carbohydrate diet
Feeding study. Composition (by proportion of calories): 20% carbohydrate, 60% fat, 20% protein

Active Comparator: Moderate carbohydrate diet Behavioral: Moderate carbohydrate diet
Feeding study. Composition (by proportion of calories): 40% carbohydrate, 40% fat, 20% protein

Active Comparator: High carbohydrate diet Behavioral: High carbohydrate diet
Feeding study. Composition (by proportion of calories): 60% carbohydrate, 20% fat, 20% protein




Primary Outcome Measures :
  1. Blood flow to the nucleus accumbens and connected striatal regions [ Time Frame: 14-20 weeks after initiation of test diet ]
    Regional cerebral blood flow (rCBF) measured using arterial spin labeling (ASL) at rest, in neuroanatomically-defined a priori regions (nucleus accumbens, caudate, putamen).


Secondary Outcome Measures :
  1. Blood flow to the hypothalamus [ Time Frame: 14-20 weeks after initiation of test diet ]
    Regional cerebral blood flow (rCBF) measured using arterial spin labeling (ASL) at rest, in neuroanatomically-defined a priori regions (hypothalamus).

  2. Functional connectivity between the hypothalamus and nucleus accumbens [ Time Frame: 14-20 weeks after initiation of test diet ]
    Blood-oxygen-level-dependent (BOLD) fMRI connectivity between neuroanatomically-defined regions of interest (hypothalamus, nucleus accumbens), measured during rest.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 18 to 55 years
  • BMI ≥ 23 kg/m2
  • BMI < 45 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
  • Community-based participants from the greater Framingham and Assabet Valley communities
  • 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:

  • Body circumference of <64 in
  • Willingness to undergo 2, 30-minute MRI scans

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:

  • Previous bariatric surgery
  • Other contraindications to MRI scanning (severe claustrophobia/extensive orthopedic hardware/pacemaker, cerebral aneurysm clip)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02300857


Sponsors and Collaborators
Brigham and Women's Hospital
Boston Children’s Hospital
Nutrition Science Initiative
New Balance Foundation
Boston Medical Center
Framingham State University
Investigators
Layout table for investigator information
Principal Investigator: Laura M. Holsen, Ph.D. Brigham and Women's Hospital

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Laura M. Holsen, Assistant Professor of Psychiatry, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02300857     History of Changes
Other Study ID Numbers: 2014P001880
First Posted: November 25, 2014    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Nutrients
Growth Substances
Physiological Effects of Drugs