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

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03020186
Acronym
DIRECT-PLUS
Enrollment
294
Registered
2017-01-13
Start date
2017-01-31
Completion date
2019-03-31
Last updated
2019-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Abdominal Obesity Metabolic Syndrome

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.

Interventions

OTHERPhysical activity
OTHERPhysical activity+ MED diet
OTHERPhysical 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.

Sponsors

Harvard School of Public Health (HSPH)
CollaboratorOTHER
University of Leipzig
CollaboratorOTHER
Ben-Gurion University of the Negev
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
Abdominal fat18 monthsChanges in visceral fat (MRI)
Hepatic fat18 monthsChanges in hepatic fat (MRI)
Obesity6, 14, 18 monthsChanges in body weight and waist circumference

Secondary

MeasureTime frameDescription
Brain anatomy18 monthsChanges in hippocampus volume, diffusion Tensor Imaging (MRI)
Cognitive function-MRI18 monthsChanges in resting state connectivity (MRI, sub-study)
Cognitive function18 monthscognitive tests
Cardiac state18 monthsChanges in cardiac anatomy (MRI, substudy)
Endothelial dysfunction18 monthsChanges endothelial function (ECG)
Lipid profile6 , 14 and 18 monthsChanges in lipid biomarkers (blood draw)
Glycemic control6 , 14 and 18 monthsChanges in glycemic biomarkers (blood draw)
Inflammatory state6 , 14 and 18 monthsChanges in inflammatory biomarkers (blood draw)
Metabolomic18 monthsChanges in sub-lipids (blood draw)
Liver function (blood biomarkers)6 and 18 monthsChanges in liver function biomarkers (blood draw)
Genetic signaturebaselineSNPs associated with fat distribution and visceral fat
Epigenetics18 monthschanges in mRNAs
Well being18 monthsassessed by questionnaire
Fecal microbiota profile6, 14, 18 monthsDiversity Index as a key measure
24h- continuous glucose levels2 weeks24h dynamics of glucose using continuous glucose monitor. substudy

Countries

Israel

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 3, 2026