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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 : Recruiting
First Posted : January 13, 2017
Last Update Posted : January 13, 2017
Sponsor:
Collaborators:
Harvard School of Public Health
University of Leipzig
Information provided by (Responsible Party):
Iris Shai, Ben-Gurion University of the Negev

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.

Condition or disease Intervention/treatment Phase
Abdominal Obesity Metabolic Syndrome Other: Physical activity Other: Physical activity+ MED diet Other: Physical activity+green MED diet Not Applicable

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS
Study Start Date : November 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 .
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.
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.
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 10 and 12 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.




Primary Outcome Measures :
  1. Abdominal fat [ Time Frame: 18 months ]
    Changes in visceral fat (MRI)

  2. Hepatic fat [ Time Frame: 18 months ]
    Changes in hepatic fat (MRI)

  3. Obesity [ Time Frame: 6, 18 months ]
    Changes in body weight and waist circumference


Secondary Outcome Measures :
  1. Brain anatomy [ Time Frame: 18 months ]
    Changes in hippocampus volume, diffusion Tensor Imaging (MRI)

  2. Cognitive function-MRI [ Time Frame: 18 months ]
    Changes in resting state connectivity (MRI, sub-study)

  3. Cognitive function [ Time Frame: 18 months ]
    cognitive tests

  4. Cardiac state [ Time Frame: 18 months ]
    Changes in cardiac anatomy (MRI, substudy)

  5. Cardiac state [ Time Frame: 18 months ]
    Changes in cardiac function (MRI, substudy)

  6. Endothelial dysfunction [ Time Frame: 18 months ]
    Changes endothelial function (ECG)

  7. Lipid profile [ Time Frame: 6 and 18 months ]
    Changes in lipid biomarkers (blood draw)

  8. Glycemic control [ Time Frame: 6 and 18 months ]
    Changes in glycemic biomarkers (blood draw)

  9. Inflammatory state [ Time Frame: 6 and 18 months ]
    Changes in inflammatory biomarkers (blood draw)

  10. Metabolomic [ Time Frame: 18 months ]
    Changes in sub-lipids (blood draw)

  11. Metabolomic [ Time Frame: 18 months ]
    Changes in sub-proteins ( blood draw)

  12. Liver function (blood biomarkers) [ Time Frame: 6 and 18 months ]
    Changes in liver function biomarkers (blood draw)

  13. Genetic signature [ Time Frame: baseline ]
    SNPs associated with fat distribution and visceral fat

  14. Epigenetics [ Time Frame: 18 months ]
    changes in mRNAs

  15. Epigenetics [ Time Frame: 18 months ]
    changes in genes' methylation

  16. Well being [ Time Frame: 18 months ]
    assessed by questionnaire

  17. Fecal microbiota profile [ Time Frame: 6, 18 months ]
    Diversity Index as a key measure

  18. 24h- continuous glucose levels [ Time Frame: 2 weeks ]
    24h dynamics of glucose using continuous glucose monitor. substudy



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03020186


Contacts
Contact: Iris Shai, PhD +972-5793040 irish@bgu.ac.il
Contact: Iris Shai, PhD ++972-8-6477443/9

Locations
Israel
Nuclear research center Negev Recruiting
Dimona, Israel
Contact: Dov Brikner, MD         
Sponsors and Collaborators
Ben-Gurion University of the Negev
Harvard School of Public Health
University of Leipzig
Investigators
Principal Investigator: Iris Shai, PhD Ben-Gurion University of the Negev

Responsible Party: Iris Shai, Principle investigator, Ben-Gurion University of the Negev
ClinicalTrials.gov Identifier: NCT03020186     History of Changes
Other Study ID Numbers: BGU
First Posted: January 13, 2017    Key Record Dates
Last Update Posted: January 13, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Metabolic Syndrome X
Obesity, Abdominal
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Obesity
Overnutrition
Nutrition Disorders