Brain Response to Dietary Interventions
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      In order to better understand how commonly used dietary interventions for obesity influence
      brain activity and in turn people's ability to adhere to their healthy nutrition plan, the
      investigators need to study how people's brains react to food cues while undergoing such
      interventions. Our study will add to our understanding of neural (brain) regulation of
      hedonic and homeostatic mechanisms (i.e. pleasure and hunger) in influencing adherence to
      calorie-reduced eating plans.
    

Detailed description: 
      Recruitment of subjects: Advertisements for the recruitment of participants will be posted on
      social media and notice boards within the Texas Tech University (TTU) including the web-based
      notice boards (including but not limited to Tech Announce, Craig's List). Announcements will
      also be made using the same materials targeting the local community through paid
      advertisement in local print and online media outlets (e.g. newspapers) and through flyers
      distributed within area medical clinics and fitness centers. Thirty-two obese (BMI > 30) male
      and female subjects will be enrolled with the intended completion of at least 30 (15 per
      group).

      Pre-Screening (Telephone): Individuals who express an interest in participating will be
      contacted by a graduate or undergraduate research assistant who will administer a structured
      telephone interview to: 1) provide information related to the requirements of the study,
      along with potential risks and benefits 2) Screen for eligibility based on specific inclusion
      and exclusion criteria. All potential subjects will be informed that their responses will
      remain confidential and that taking part in the screening interview in no way obligates them
      to participate.

      Potential participants who meet participation criteria as assessed via the telephone
      prescreening process will be contacted by the study team via email/phone within 48 hours
      following the interview to inform of eligibility (or ineligibility) and to schedule an
      initial, in person assessment (Visit 1) if deemed eligible.

      Visit 1 (Screening and Consent): This in-person screening visit will include the following:
      Participants will be provided with the Behavioral Medicine and Translational Research (BMTR)
      Health & Weight History Form to complete upon arrival at the clinic. Weight, height, BMI and
      body fat percentage via bio-electrical impedance analysis (BIA) using the TANITA BC-418
      segmental body composition analyzer (TANITA Corporation of America Inc., IL, USA) and body
      composition analysis unit; measured blood pressure (BP) via Omron Digital BP Monitor
      HEM-907XL (Omron Healthcare Inc., IL, USA) will be obtained.

      If inclusion/exclusion criteria are met; informed consent will be obtained and the
      participant will be considered 'enrolled' in the study at that time. Participants will be
      scheduled for 2 scanning visits (visits 2 and 5) and the 2 check in visits (visits 3 and 4)
      at this time and instructed on the procedures for these subsequent visits. At completion of
      Visit 1 the participants will be told to make no deviation from their standard diet until
      after their initial fMRI scan visit (visit 2).

      Special Scheduling Considerations: The phase of the menstrual cycle may have an effect on
      cravings. The first scanning session of pre-menopausal female participants will be scheduled
      in the second half of the follicular phase of a menstrual cycle (i.e. 10th - 14th day of a
      menstrual cycle). Thus, the second scanning session, which will be performed 3 weeks after
      the first session, will be performed in the first half of the follicular phase (approximately
      between the 3rd and 7th days) of the next menstrual cycle. This will ensure that both
      scanning sessions will be performed within the follicular phase.

      Visit 2 (Pre-intervention fMRI Scan):

        1. Participants will be requested to refrain from taking any items of food or beverages
           (except water) for 8 hours minimum prior to the scanner visit.

        2. The participants will also be advised to refrain from i) tobacco use in any form ii) the
           intake of alcohol or caffeine in any form within the 24 hours prior to the scanning
           visit.

        3. The participants will be asked to complete the following paper & pencil measures in an
           adjacent room prior to entering the fMRI scanner: i) Food Craving Inventory; ii) Power
           of Food Scale; iii) Three-Factor Eating Questionnaire; iv) Yale Food Addiction Scale; v)
           Visual Analogue Scales (VAS) on the dimensions of hunger, satiety, thirst, fullness and
           emptiness.

        4. The duration of each scan will be 45-60 minutes (including the time spent on placing
           each participant in the scanner).

        5. After the scanning is complete, each participant will be taken to an adjacent room and
           VAS will be administered again immediately after the scan (total duration 30 minutes)
           according to the procedures outlined in (c) above.

        6. The participants will then be shown on a laptop computer, a random subset of 60 images
           from the set to which the participants were exposed to, during the fMRI scanning
           paradigm, randomly mixed with 60 other images to which the participants were not exposed
           with a task of recognizing the images that were presented in the scanning paradigm
           (duration 15-20 minutes).

      fMRI scanning paradigm: An event-related design will be used for all stimulus presentations.
      120 images of two categories (food items and objects) will be displayed on an LCD screen and
      projected via a mirror attached to the head coil. Images of food and objects will be matched
      for contrast, brightness, size and resolution. Food images will represent a continuous
      spectrum of highly rewarding to less rewarding items, while selected common objects (e.g. a
      paper clip) will be deemed 'neutral'. Each participant will be shown a fixation cross lasting
      for 2000-4000ms. Then, each visual image will be presented for 5000-6000ms with 'overlapped'
      opportunity for rating of the stimulus by the subject (i.e., ratings performed while viewing
      the image). During the presentation of each image, participants will be required to answer
      the question "How much do you want it now?" on a 1-7 Likert scale using fiber optic buttons.
      This sequence will be conducted 30 times, with different images to complete each run. Eight
      such runs will comprise each scanning session. Following the stimulus presentation phase (EPI
      scan), a T1-weighted structural scan (SS) lasting approximately 5 minutes will be obtained
      followed by a diffusion tensor imaging (DTI) scan (6 minutes) to assess white-matter
      connectivity.

      Immediately following the initial fMRI scan subjects will be randomly assigned to one of the
      2 arms of the study: the Total Meal Replacement (TMR) group or the Typical Diet (TD) group
      (16 participants per group). Each arm will maintain 1120 kcal/day target caloric intake.

      TMR Group: Optifast™ 800 total meal replacement shakes (1120 kcal/day) will provide all
      nutrition (no additional food). One week supply of meal replacement product is provided.

      TD Group: Participants will be directed to use portion control to maintain a calorie level of
      1120 kcal per day. Subjects will be provided resources to assist them in determining caloric
      content of foods eaten.

      Visits 3 and 4 (Check-in Visits): Subjects of both groups will be requested to return to the
      BMTR lab at 1 week intervals over the first 2 weeks following visit 2 to be weighed, have
      blood pressure taken, review any issues and report adherence variations from protocol
      (including additional caloric intake). Subjects of the TMR group will receive the next week's
      product at each visit. Subjects of the TD group will be requested to provide a written list
      of daily calorie intake of the past week at each visit.

      Visit 5 (post-intervention Scanning Visit): Preparation for the visit, completion of pencil
      and paper measures, procedure of scanning and the post-scan memory task will be similar to
      visit 2. In addition, BIA, BP, weight and height will be measured and BMI will be calculated.

      Analysis: fMRI analysis will be carried out using a standard mixed effects model implemented
      in FMRIB Software Library (FSL). Specifically, analysis of fMRI data will be focused on
      identifying pre-post differences in both the location and relative magnitude of whole brain
      activation patterns within and between members of each group (TMR vs. TD). Pre-planned
      comparisons will also be made for specific regions of interest: a) food-reward related areas
      (e.g. insula, orbito-frontal cortex, anterior cingulate cortex, and amygdala); b) reward
      calculating regions (e.g. nucleus accumbens and ventral striatum), c) memory and emotion
      related areas (e.g. hippocampus and amygdala); d) homeostatic circuitry (i.e. hypothalamus)
      and cortical areas exerting executive control (e.g. pre-frontal cortex). Both structural and
      functional connectivity between the considered regions of interest will also be modeled and
      compared between and within groups. Demographic, health, weight history and psychosocial
      variables may be included as covariates in specific analyses as indicated.
    

Intervention name(s): Low calorie total meal replacement; Low calorie typical diet
Intervention type(s): Other; Other
Intervention description(s): Participants will be provided instruction in the appropriate use of the meal replacement product. The participants will be directed to refrain from all items of food for a period of 21 days except for the meal replacement products and vitamin supplements provided by the investigators (1120 kcal/day). Optifast™ 800 total meal replacement shakes will be provided to the participants for the 21 day intervention period.; Participants will be directed to use portion control to maintain a calorie level no greater than 1120 kcal per day. The participants will be directed to continue to consume food and beverage items that are representative of their typical diet (with the exception of reduced portions). Participants will be provided resources to assist them in determining caloric content of foods eaten.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Calorie restriction; Meal replacement; fMRI; Food-cue reactivity; Obesity