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Activation of Brain Centers by Short-term Walnut Consumption in Obesity

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.