Activation of Brain Centers by Short-term Walnut Consumption in Obesity
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional

Summary: 
      The purposes of the study are:

        -  Study Aim 1. To assess the mechanisms underlying the biological effects of short-term
           walnut consumption on appetite with functional magnetic resonance imaging (fMRI) and
           assessing neurocognitive function/memory

        -  Study Aim 2. To investigate the effects of walnut consumption (48g per day over 5 days)
           on appetite and satiety by analyzing molecules which regulate energy homeostasis such as
           adipokines, as well as resting metabolic rate which measures energy expenditure.

        -  Study Aim 3. To investigate the effects of walnuts (48g per day over 5 days) on insulin
           resistance, lipids, and inflammatory markers in obesity as well as the effect of walnuts
           when consumed as part of a mixed meal, on glucose excursions, insulin secretion and the
           excretion of gut peptides and free fatty acids.
    

Detailed description: 
      Study Overview:

      The study is a short-term, pilot, double-blinded, randomized, cross-over inpatient study
      testing the effects of either 48 g of walnuts per day vs. an ad libitum diet without walnuts
      on appetite and satiety, insulin resistance, basal metabolic rate, lipids, adipokines, heart
      rate, vascular reactivity, and markers of inflammation. The investigators propose that
      subjects stay in the controlled environment of our Clinical Research Center (CRC) for the
      entire duration of each arm of the study (5 days), which will be separated from the other arm
      by a one month long wash out period. Walnuts/placebo administration will be in the form of a
      milkshake with identical macronutrient content. Each study subject will be fed an identical
      diet during both admissions to minimize variability.

      Study Design:

      Screening: Potential subjects will be initially screened through telephone to determine that
      they are eligible for inclusion in the study according to the inclusion/exclusion criteria.
      If they pass the phone screening then they will be asked to come at CRC for a screening
      visit. They will have a detailed medical history, physical exam, fasting lab tests such as
      fructosamine, international normalized ratio (INR), prothrombin time (PT), complete blood
      count (CBC), metabolic panel including glucose and lipid profile, electrocardiogram (EKG),
      vitals, anthropometry and pregnancy test for women and if eligible for participation they
      will sign the informed consent of the study.

      Subjects meeting eligibility criteria will be randomized to start with either the active
      intervention or placebo. Subjects will complete a 3-day food diary prior to visit 1 to
      document baseline diet. They will also meet the dietitian who will advise them on following a
      prudent diet and maintaining a stable exercise pattern for 2 weeks before the first visit and
      between both visits. Subjects will also be advised to avoid walnuts during this period.
      Subjects will also be required to maintain their weight +/- 3kg between screening and between
      study visits.

      In-patient CRC Admission: In order to ensure stable study conditions, eligible subjects will
      be asked to stay in the CRC of the Beth Israel Deaconess Medical Center (BIDMC) for a period
      of 5 days on each of the study visits. They will receive advice on isocaloric diet but will
      be allowed to eat ad libitum and will be randomized prior to the first visit regarding the
      sequence of the study visits. All subjects will have 2 5-day visits to the CRC, one where
      they receive active milkshake containing 48g of walnuts daily in a single morning meal
      instead of breakfast, and another where they receive a "placebo" milkshake without nuts.
      Subjects will have their hunger assessed using visual analog scales before breakfast, lunch
      and dinner each day. These inpatient visits will be separated from each other by a 1-month
      washout period. Subjects and investigators will be blinded regarding the study sequence.

      For each of the inpatient series, subjects will be admitted to CRC the night before the first
      day of the study. On day 1, subjects will have baseline measures such as vitals,
      anthropometry, brief medical history, physical exam, pregnancy test for women. Prior to
      leaving the CRC on day 5, subjects will again have vitals, blood draws for several markers
      including fructosamine, lipid panel, high sensitivity c-reactive protein (hsCRP), adiponectin
      and leptin, resting metabolic rate (RMR), anthropometry and body composition measures. On
      this last day, they will also undergo neurocognitive testing and an fMRI at the fasting state
      while viewing food cues and a mixed meal challenge either with or without walnuts. Subjects
      will be discharged from the CRC after their final testing and after evaluating the milkshake
      they were consuming on day 5 and will resume their normal diet for a period of 4 weeks after
      which time they will return to the CRC for a further 5 days for the second study visit. Prior
      Visit 2 participants will complete another 3-day food diary. If they received placebo
      milkshake on the first visit, they will have the walnut milkshake on the second visit and
      vice-versa.
    

Intervention name(s): Walnut shake; Placebo shake
Intervention type(s): Other; Other
Intervention description(s): walnut shake will be administered for 5 days as a morning snack instead of a typical breakfast; placebo shake will be administered for 5 days as a morning snack instead of a typical breakfast
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: walnuts; brain; appetite; energy intake; obesity