Study of Effects From Gastric Bypass Weight Loss on Brain Tissue
Condition: Weight Loss
MeSH terms: Body Weight; Weight Loss
Study type: Observational

Summary: 
      This study will evaluate how large, intentional weight reduction affects the human brain and
      possible ways to reverse the changes associated with excess body weight. Subtle changes in
      some brain regions occur in people who are overweight. Such changes may involve the
      regulation of eating behavior, though it is not clear whether the changes were present before
      weight gain or are a consequence. Magnetic resonance imaging (MRI) will be used to study
      local structures of the brain.

      Patients ages 18 to 45 who are undergoing gastric bypass surgery and who are not pregnant or
      breastfeeding may be eligible for this study. A study group of lean participants will serve
      as controls. Patients will visit the Phoenix Indian Medical Center for about 3 days at a time
      for tests. They will have a medical examination, electrocardiogram, and tests of blood and
      urine. Questionnaires they will complete involve patients' moods and possible influence on
      eating behaviors, as well as food preferences. A taste test, smell test, and assessment of
      decision-making processes will be conducted. An oral glucose tolerance test involves a needle
      placed intravenously (IV) in the arm, for drawing blood after patients drink a sugar
      solution. The test takes about 3-1/2 hours, with six blood samples taken (about 2 tablespoons
      total). A meal test also includes use of an IV line. After patients consume a liquid meal,
      blood will be collected to analyze levels of blood sugar and hormones. For the DEXA scan,
      which measures body composition, patients will lie still while low-dose X-rays are used for 5
      to 10 minutes. Urine will be collected for 1 whole day, to measure cortisol, a hormone. The
      MRI scan uses a strong magnetic field to obtain images of body organs and tissues. Patients
      having any metal in the body that may interfere with the scanning machine should not have
      this test. For the MRI procedure, patients will lie on a table that slides into the enclosed
      tunnel of the scanner and be asked to lie still. Patients will be able to communicate with
      the MRI staff at all times during the scan, and they may ask to be removed from the machine
      at any time.
    

Detailed description: 
      BACKGROUND: We have identified subtle changes in some brain regions of obese subjects by
      using a new computerized technique (voxel-based morphometry, VBM) which allows for studying
      the local structure of the brain by taking very detailed pictures of the brain through
      magnetic resonance imaging (MRI) and then processing these images with sophisticated
      statistical software. Some of these regions may interfere with an obese person's ability to
      predict future consequences of his or her eating behaviors. These changes may explain why
      people have difficulty losing weight. However, it is not clear whether these changes in the
      brain are present before or are a consequence of weight gain.

      OBJECTIVES: The main aim of this study will be to evaluate the effects of a large and
      intentional weight reduction on the brains of obese individuals for assessing the possible
      reversal of the changes associated with excess body weight. Additional objectives will be a)
      to determine the possible behavioral correlates of the changes in brain tissue composition
      associated with a large and intentional weight reduction and b) to confirm the results of our
      previous exploratory analysis showing that human obesity is associated with changes in brain
      structure in areas related to the regulation of eating behavior.

      DESIGN: This is a longitudinal protocol mainly focused on obese patients undergoing roux-en-Y
      gastric bypass (RYGBP), which represents the most effective approach currently available to
      achieving substantial weight loss, thus maximizing our chances of detecting significant
      changes in brain tissue composition. Therefore, we propose to study brain morphology and the
      metabolic and behavioral characteristics of 40 obese patients undergoing RYGBP prior to and
      3, 6, 12, 24, and 48 months after the surgery. Forty lean subjects (at 0, 12, 24, and 48
      months) will also be studied for comparison.

      OUTCOME MEASURES: The volumes of the different components of the brain by VBM of MRI
      pictures; metabolic parameters relevant to the relationship between obesity and the brain by
      measuring fasting concentrations and postprandial responses of some metabolites; the ability
      to regulate reward and behavior by specific tasks and questionnaires; the ability to detect
      and discriminate smells by olfaction tests.
    

Keywords: Obesity; Gray Matter; Eating Behavior; Brain MRI; Body Weight Regulation