Clinical Trial: Effects of Green-MED Diet Via the Gut-fat-brain Axis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS

Brief Summary: Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat (green-MED diet) may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase.

Detailed Summary: The investigators aim to compare the effect of green-MED diet+ physical activity (PA) vs. MED diet+ PA vs. PA on the gut-fat-brain axis and to explore the additional contribution of autologous fecal microbiota derived at the rapid weight loss phase on regain phase. Mediterranean (MED) diet, richer in plants/seeds (and dietary polyphenols) and low in processed meat may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. The investigators hypothesize that long-term intake of this diet will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The investigators further hypothesize that lifestyle intervention might modify the gut microbiota profile and that autologous fecal microbiota supplement derived from the time of maximal weight loss might halt the expected subsequent regain phase. The investigators will follow the participants with magnetic resonance imaging (MRI) that will include abdominal and hepatic fat, cardiac and anatomic/functional brain assessments. The investigators will perform cognitive tests and will measure changes in gut microbiota and sub-metabolomic profiling. The trial will be performed in an isolated workplace (the Nuclear Research Center) which holds an exclusive cafeteria that provides free, dietary -monitored, lunch, and an internal medical department. The exclusive nutritional profile of walnuts, with its relative high polyphenols content and unique composition, may benefit several health outcomes. Epidemiologic studies and RCTs suggest that walnuts consumption is associated with better weight status, adiposity measures and cardiometabolic state. However, some individuals avoid walnuts because they are calorie-dense
Sponsor: Ben-Gurion University of the Negev

Current Primary Outcome:

  • Abdominal fat [ Time Frame: 18 months ]
    Changes in visceral fat (MRI)
  • Hepatic fat [ Time Frame: 18 months ]
    Changes in hepatic fat (MRI)
  • Obesity [ Time Frame: 6, 18 months ]
    Changes in body weight and waist circumference


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Brain anatomy [ Time Frame: 18 months ]
    Changes in hippocampus volume, diffusion Tensor Imaging (MRI)
  • Cognitive function-MRI [ Time Frame: 18 months ]
    Changes in resting state connectivity (MRI, sub-study)
  • Cognitive function [ Time Frame: 18 months ]
    cognitive tests
  • Cardiac state [ Time Frame: 18 months ]
    Changes in cardiac anatomy (MRI, substudy)
  • Cardiac state [ Time Frame: 18 months ]
    Changes in cardiac function (MRI, substudy)
  • Endothelial dysfunction [ Time Frame: 18 months ]
    Changes endothelial function (ECG)
  • Lipid profile [ Time Frame: 6 and 18 months ]
    Changes in lipid biomarkers (blood draw)
  • Glycemic control [ Time Frame: 6 and 18 months ]
    Changes in glycemic biomarkers (blood draw)
  • Inflammatory state [ Time Frame: 6 and 18 months ]
    Changes in inflammatory biomarkers (blood draw)
  • Metabolomic [ Time Frame: 18 months ]
    Changes in sub-lipids (blood draw)
  • Metabolomic [ Time Frame: 18 months ]
    Changes in sub-proteins ( blood draw)
  • Liver function (blood biomarkers) [ Time Frame: 6 and 18 months ]
    Changes in liver function biomarkers (blood draw)
  • Genetic signature [ Time Frame: baseline ]
    SNPs associated with fat distribution and visceral fat
  • Epigenetics [ Time Frame: 18 months ]
    changes in mRNAs
  • Epigenetics [ Time Frame: 18 months ]
    changes in genes' methylation
  • Well being [ Time Frame: 18 months ]
    assessed by questionnaire
  • Fecal microbiota profile [ Time Frame: 6, 18 months ]
    Diversity Index as a key measure
  • 24h- continuous glucose levels [ Time Frame: 2 weeks ]
    24h dynamics of glucose using continuous glucose monitor. substudy


Original Secondary Outcome: Same as current

Information By: Ben-Gurion University of the Negev

Dates:
Date Received: January 9, 2017
Date Started: November 2016
Date Completion: October 2020
Last Updated: January 11, 2017
Last Verified: January 2017