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Completed

NCT Number: NCT03020186

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

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.

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Key information

Age range

30 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Nuclear research center Negev

Dimona, Israel

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Physical activity

Other

Physical activity+ MED diet

Other

Physical activity+green MED diet

Other

****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.

Primary outcomes

  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, 14, 18 months

    Changes in body weight and waist circumference

Secondary outcomes

  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 , 14 and 18 months

    Changes in lipid biomarkers (blood draw)

  8. Glycemic control

    Time frame: 6 , 14 and 18 months

    Changes in glycemic biomarkers (blood draw)

  9. Inflammatory state

    Time frame: 6 , 14 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, 14, 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

Sponsors and collaborators

Lead sponsor

Ben-Gurion University of the Negev

Other

Collaborators

  • Harvard School of Public Health (HSPH)
  • University of Leipzig

Registry information

Official study title

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

Acronym: DIRECT-PLUS

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Jan 13, 2017
Registry last updated
Jul 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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