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Effects of Green-MED Diet Via the Gut-fat-brain Axis (DIRECT-PLUS)

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ClinicalTrials.gov Identifier: NCT03020186
Recruitment Status : Completed
First Posted : January 13, 2017
Last Update Posted : July 15, 2019
Sponsor:
Collaborators:
Harvard School of Public Health
University of Leipzig
Information provided by (Responsible Party):
Iris Shai, Ben-Gurion University of the Negev

Tracking Information
First Submitted Date  ICMJE January 9, 2017
First Posted Date  ICMJE January 13, 2017
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE January 2017
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • 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, 14, 18 months ]
    Changes in body weight and waist circumference
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • 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 , 14 and 18 months ]
    Changes in lipid biomarkers (blood draw)
  • Glycemic control [ Time Frame: 6 , 14 and 18 months ]
    Changes in glycemic biomarkers (blood draw)
  • Inflammatory state [ Time Frame: 6 , 14 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, 14, 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 Measures  ICMJE
 (submitted: January 11, 2017)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Green-MED Diet Via the Gut-fat-brain Axis
Official Title  ICMJE 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 Description 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, and fear that they will promote weight gain. Walnuts contain numerous well-characterized beneficial nutritional components, such as unsaturated fats, especially omega-3 fatty acids, dietary fibers, and high levels of vitamins and minerals. Among other well-recognized components, nuts are highly rich in polyphenols, mainly flavonoids. Polyphenols may potentially interact with physical activity and promote neurogenesis; a process that may significantly contribute to the brain's ageing process. Similarly, the polyphenol epigallocatechin-3-gallate (EGCG, a type of catechin found in green tea), was proposed to exert neuroprotective effects. New specific developed strain of duckweed [Wolffia globose, "Mankai"] , an aquatic plant, which might serve as a protein source and contains all the 9 essential and the 6 conditional amino acids. "Mankai" [(Generally recognized as safe (GRAS)] is a cultivated strain of Wolffia globosa, which is an aquatic plant, part of the family of plants known commonly as duckweeds. Duckweeds are very simple flowering aquatic plants, which float on or just beneath the surface of still or slow-moving bodies of water. There is a long history of the use of Wolffia species, in particular Wolffia Globosa, as food, especially in Southeast Asia: Burma, Laos and northern Thailand, where it has been used as a vegetable for many generations. The nutritional composition of "Mankai" has been determined and found to be high in protein, containing all the essential and conditionally essential amino acids, dietary fibers and several vitamins and minerals.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Abdominal Obesity Metabolic Syndrome
Intervention  ICMJE
  • Other: Physical activity
  • Other: Physical activity+ MED diet
  • Other: Physical activity+green MED diet
    ****Sub-study from all 3 main arms: Autologous fecal microbiota supplement intervention derived from the time of maximal weight loss: At the 6-month time period, the time of anticipated greatest weight reduction, participants's feces samples will be processed to capsulized inocula. Samples will be frozen within 2 hours and will be kept at -80c pending analysis. Participants will be randomized to receive either research capsules or identical placebo capsules between 8 and 14 months time period. Placebo capsules will consist of a combination of powdered cocoa and vegetable gelatin in normal saline/glycerol and will be identical in appearance to research capsules.
Study Arms  ICMJE
  • Placebo Comparator: Physical activity
    Physical activity (PA) group will receive free gym memberships and the instruction necessary to engage in moderate-intensity physical activity, ~80% of which will have an aerobic component. The participants will get basic health promoting guideline for healthy diet .
    Intervention: Other: Physical activity
  • Experimental: Physical activity+ MED diet
    On top of the PA intervention described in Arm 1, the participants will be guided for moderate weight loss with a traditional Mediterranean (MED) diet, low in simple carbohydrates. The diet will include 1oz/day of walnuts that will be provided free of charge.
    Intervention: Other: Physical activity+ MED diet
  • Experimental: Physical activity+ green-MED diet
    On top of the PA intervention described in Arm 1, the participants will guided for moderate weight loss with a MED diet, low in simple carbohydrates that will be rich in plants and polyphenols and low in processed meat. The diet will include 1oz/day of walnuts, 3-4 cups/day of green tea and ~500cc green shake/dinner based on specific strain of duckweed [Wolffia globose, "Mankai"], an aquatic plant, which might serve as a plant protein source. All the above will be provided free of charge.
    Intervention: Other: Physical activity+green MED diet
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 11, 2019)
294
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2017)
270
Actual Study Completion Date  ICMJE March 2019
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

age >30 years with abdominal adiposity (waist circumference: men > 102 cm, women > 88 cm) or dyslipidemia (TG>150mg/dl and HDL-c <40mg/dL for men and <50mg/dL for women)

Exclusion Criteria:

Individuals who may not be able to partake in PA in the gym; TGs>400 mg/dL; serum creatinine>2 mg/dL; disturbed liver function; major illness that might require hospitalization; pregnant or lactating women; presence of active cancer, is receiving or received chemotherapy in the last three years; participation in another trial; participants who are treated with Coumadin (warfarin) - given its interaction with vitamin K and high level of this vitamin in "Mankai" green shake; pacemaker or platinum implant, because of the impossibility of MRI screening.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03020186
Other Study ID Numbers  ICMJE BGU
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Iris Shai, Ben-Gurion University of the Negev
Study Sponsor  ICMJE Ben-Gurion University of the Negev
Collaborators  ICMJE
  • Harvard School of Public Health
  • University of Leipzig
Investigators  ICMJE
Principal Investigator: Iris Shai, PhD Ben-Gurion University of the Negev
PRS Account Ben-Gurion University of the Negev
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP