Abdominal Obesity Metabolic SyndromeDIRECT-PLUSNCT03020186
Effects of Green-MED Diet Via the Gut-fat-brain Axis
A study testing Physical activity, Physical activity+ MED diet and Physical activity+green MED diet in people with Abdominal Obesity Metabolic Syndrome, run by Ben-Gurion University of the Negev at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and olderHealthy volunteers can take part
- Conditions the study is for
- Abdominal Obesity Metabolic Syndrome
- What is being tested?
- Physical activity, Physical activity+ MED diet and Physical activity+green MED diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 294 participants
- Where
- 1 siteIsrael
- Study dates
- Jan 2017to Mar 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS
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.
Read the 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.
- Conditions
- Abdominal Obesity Metabolic Syndrome
- Being tested
- Physical activity, Physical activity+ MED diet, Physical activity+green MED diet
- Medical subject headings
- Abdominal obesity metabolic syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physical activityOther
Physical activity+ MED dietOther
Physical activity+green MED dietOther
****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 group | Role | What they receive |
|---|---|---|
| Physical activity | Placebo comparator | 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 . Receives: Other: Physical activity |
| Physical activity+ MED diet | Experimental | 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. Receives: Other: Physical activity+ MED diet |
| Physical activity+ green-MED diet | Experimental | 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. Receives: Other: Physical activity+green MED diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Abdominal fat
Changes in visceral fat (MRI)
Measured: 18 months
Hepatic fat
Changes in hepatic fat (MRI)
Measured: 18 months
Obesity
Changes in body weight and waist circumference
Measured: 6, 14, 18 months
Secondary outcomes (18)
Brain anatomy
Changes in hippocampus volume, diffusion Tensor Imaging (MRI)
Measured: 18 months
Cognitive function-MRI
Changes in resting state connectivity (MRI, sub-study)
Measured: 18 months
Cognitive function
cognitive tests
Measured: 18 months
Cardiac state
Changes in cardiac anatomy (MRI, substudy)
Measured: 18 months
Cardiac state
Changes in cardiac function (MRI, substudy)
Measured: 18 months
Endothelial dysfunction
Changes endothelial function (ECG)
Measured: 18 months
Lipid profile
Changes in lipid biomarkers (blood draw)
Measured: 6 , 14 and 18 months
Glycemic control
Changes in glycemic biomarkers (blood draw)
Measured: 6 , 14 and 18 months
Inflammatory state
Changes in inflammatory biomarkers (blood draw)
Measured: 6 , 14 and 18 months
Metabolomic
Changes in sub-lipids (blood draw)
Measured: 18 months
Metabolomic
Changes in sub-proteins ( blood draw)
Measured: 18 months
Liver function (blood biomarkers)
Changes in liver function biomarkers (blood draw)
Measured: 6 and 18 months
Genetic signature
SNPs associated with fat distribution and visceral fat
Measured: baseline
Epigenetics
changes in mRNAs
Measured: 18 months
Epigenetics
changes in genes' methylation
Measured: 18 months
Well being
assessed by questionnaire
Measured: 18 months
Fecal microbiota profile
Diversity Index as a key measure
Measured: 6, 14, 18 months
24h- continuous glucose levels
24h dynamics of glucose using continuous glucose monitor. substudy
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Abdominal Obesity Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 294 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ben-Gurion University of the Negev
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard School of Public Health (HSPH), University of Leipzig
- Responsible party
- Principal investigator, Iris Shai, Ben-Gurion University of the Negev
- Investigators
- Iris Shai, PhD, Principal investigator, Ben-Gurion University of the Negev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03020186
- Sponsor's protocol ID
- BGU
- Acronym
- DIRECT-PLUS
- Status last verified
- Jan 2017
- First submitted
- 9 Jan 2017
- Last updated
- 15 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Klein H, Alufer L, Goldberg Toren DT, Pachter D, Kamer O, Ebstein Karamani N, Chassidim Y, Shelef I, Rudich A, Yoel U, Ben-Arie G, Zelicha H, Yaskolka Meir A, Tsaban G, Bartal C, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Qi L, Stampfer MJ, Hu FB, Shai I. Lifestyle-Induced Visceral Fat Loss as a Key Target for Durable Cardiometabolic Health: MRI-Assessed 5- and 10-Year Follow-Up After 2 Clinical Trials. Circulation. 2026 Jul 7;154(1):16-27. doi: 10.1161/CIRCULATIONAHA.125.079009. Epub 2026 Jun 2.
PubMed 42227111Pachter D, Klein H, Kamer O, Goldberg Toren DT, Alufer L, Ebstein Karamani N, Atlas T, Yaary A, Hagbi I, Chassidim Y, Shelef I, Salti M, Beyer F, Witte V, Rudich A, Yoel U, Ben-Arie G, Yaskolka Meir A, Kaplan A, Tsaban G, Zelicha H, Bartal C, Qi L, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Wang DD, Stampfer MJ, Hu FB, Avidan G, Shai I. Sustained visceral fat loss is associated with attenuated brain atrophy and improved cognitive function in late midlife. Nat Commun. 2026 Mar 26;17(1):4434. doi: 10.1038/s41467-026-71141-4.
PubMed 41888134Klein H, Pachter D, Goldberg Toren DT, Kamer O, Alufer L, Ebstein Karamani N, Chassidim Y, Shelef I, Rudich A, Yoel U, Ben-Arie G, Zelicha H, Yaskolka Meir A, Tsaban G, Bartal C, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Qi L, Stampfer MJ, Hu FB, Shai I. How effective is rejoining a long-term weight loss program? The 5- and 10-year MRI-assessed Follow Interventions Trial (FIT) project. BMC Med. 2026 Jan 30;24(1):121. doi: 10.1186/s12916-026-04663-9.
PubMed 41612310Pachter D, Yaskolka Meir A, Kaplan A, Tsaban G, Zelicha H, Rinott E, Levakov G, Finkelstein O, Shelef I, Salti M, Beyer F, Witte V, Kloting N, Isermann B, Ceglarek U, Riklin Raviv T, Bluher M, Stumvoll M, Wang DD, Hu FB, Stampfer MJ, Avidan G, Shai I. Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial. Clin Nutr. 2025 Oct;53:99-108. doi: 10.1016/j.clnu.2025.08.021. Epub 2025 Aug 23.
PubMed 40897150Yaskolka Meir A, Tsaban G, Rinott E, Zelicha H, Schwarzfuchs D, Gepner Y, Rudich A, Shelef I, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Kloting N, Keller M, Kovacs P, Qi L, Wang DD, Liang L, Hu FB, Stampfer MJ, Shai I. Individual response to lifestyle interventions: a pooled analysis of three long-term weight loss trials. Eur J Prev Cardiol. 2025 Nov 11;32(16):1660-1670. doi: 10.1093/eurjpc/zwaf308.
PubMed 40472282Klein H, Zelicha H, Yaskolka Meir A, Rinott E, Tsaban G, Kaplan A, Chassidim Y, Gepner Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Shelef I, Qi L, Li J, Hu FB, Stampfer MJ, Shai I. Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials. BMC Med. 2025 Feb 4;23(1):57. doi: 10.1186/s12916-025-03891-9.
PubMed 39901232Pachter D, Kaplan A, Tsaban G, Zelicha H, Meir AY, Rinott E, Levakov G, Salti M, Yovell Y, Huhn S, Beyer F, Witte V, Kovacs P, von Bergen M, Ceglarek U, Bluher M, Stumvoll M, Hu FB, Stampfer MJ, Friedman A, Shelef I, Avidan G, Shai I. Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial. Am J Clin Nutr. 2024 Nov;120(5):1029-1036. doi: 10.1016/j.ajcnut.2024.09.013. Epub 2024 Sep 14.
PubMed 39284453Alufer L, Tsaban G, Rinott E, Kaplan A, Meir AY, Zelicha H, Ceglarek U, Isermann B, Bluher M, Stumvoll M, Stampfer MJ, Shai I. Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial. Front Endocrinol (Lausanne). 2023 Nov 14;14:1243910. doi: 10.3389/fendo.2023.1243910. eCollection 2023.
PubMed 38034010Kamer O, Rinott E, Tsaban G, Kaplan A, Yaskolka Meir A, Zelicha H, Knights D, Tuohy K, Fava F, Uwe Scholz M, Ziv O, Rubin E, Bluher M, Stumvoll M, Ceglarek U, Clement K, Koren O, Hu FB, Stampfer MJ, Wang DD, Youngster I, Shai I. Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial. Gut Microbes. 2023 Dec;15(2):2264457. doi: 10.1080/19490976.2023.2264457. Epub 2023 Oct 5.
PubMed 37796016Yaskolka Meir A, Keller M, Hoffmann A, Rinott E, Tsaban G, Kaplan A, Zelicha H, Hagemann T, Ceglarek U, Isermann B, Shelef I, Bluher M, Stumvoll M, Li J, Haange SB, Engelmann B, Rolle-Kampczyk U, von Bergen M, Hu FB, Stampfer MJ, Kovacs P, Liang L, Shai I. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial. BMC Med. 2023 Sep 25;21(1):364. doi: 10.1186/s12916-023-03067-3.
PubMed 37743489Zelicha H, Kloting N, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Chassidim Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Quayson RN, von Bergen M, Engelmann B, Rolle-Kampczyk UE, Haange SB, Tuohy KM, Diotallevi C, Shelef I, Hu FB, Stampfer MJ, Shai I. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Med. 2022 Sep 30;20(1):327. doi: 10.1186/s12916-022-02525-8.
PubMed 36175997Rinott E, Meir AY, Tsaban G, Zelicha H, Kaplan A, Knights D, Tuohy K, Scholz MU, Koren O, Stampfer MJ, Wang DD, Shai I, Youngster I. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. Genome Med. 2022 Mar 10;14(1):29. doi: 10.1186/s13073-022-01015-z.
PubMed 35264213Kaplan A, Zelicha H, Yaskolka Meir A, Rinott E, Tsaban G, Levakov G, Prager O, Salti M, Yovell Y, Ofer J, Huhn S, Beyer F, Witte V, Villringer A, Meiran N, B Emesh T, Kovacs P, von Bergen M, Ceglarek U, Bluher M, Stumvoll M, Hu FB, Stampfer MJ, Friedman A, Shelef I, Avidan G, Shai I. The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am J Clin Nutr. 2022 May 1;115(5):1270-1281. doi: 10.1093/ajcn/nqac001.
PubMed 35021194Tsaban G, Yaskolka Meir A, Zelicha H, Rinott E, Kaplan A, Shalev A, Katz A, Brikner D, Bluher M, Ceglarek U, Stumvoll M, Stampfer MJ, Shai I. Diet-induced Fasting Ghrelin Elevation Reflects the Recovery of Insulin Sensitivity and Visceral Adiposity Regression. J Clin Endocrinol Metab. 2022 Jan 18;107(2):336-345. doi: 10.1210/clinem/dgab681.
PubMed 34643713Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Kaplan A, Rosen P, Shelef I, Youngster I, Shalev A, Bluher M, Ceglarek U, Stumvoll M, Tuohy K, Diotallevi C, Vrhovsek U, Hu F, Stampfer M, Shai I. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 2021 Nov;70(11):2085-2095. doi: 10.1136/gutjnl-2020-323106. Epub 2021 Jan 18.
PubMed 33461965
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Green-MED Diet Via the Gut-fat-brain Axis; DIRECT-PLUS
- ClinicalTrials.gov ID
- NCT03020186
- Acronym / sponsor ID
- DIRECT-PLUS / BGU
- Conditions
- Abdominal Obesity Metabolic Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 294 participants (actual)
- Lead sponsor
- Ben-Gurion University of the NegevUniversity, hospital or other
- Collaborators
- Harvard School of Public Health (HSPH), University of Leipzig
- Study start
- Jan 2017 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Physical activity | Placebo comparator | Other: Physical activityPhysical 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 . |
| Physical activity+ MED diet | Experimental | Other: Physical activity+ MED dietOn 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. |
| Physical activity+ green-MED diet | Experimental | Other: Physical activity+green MED dietOn 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. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physical activity | Other | Physical activity |
| Physical activity+ MED diet | Other | Physical activity+ MED diet |
| 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. | Other | Physical activity+ green-MED diet |
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, 14, 18 months
Changes in body weight and waist circumference
18 secondary outcomes
Brain anatomy
Time frame: 18 months
Cognitive function-MRI
Time frame: 18 months
Cognitive function
Time frame: 18 months
Cardiac state
Time frame: 18 months
Cardiac state
Time frame: 18 months
Endothelial dysfunction
Time frame: 18 months
Lipid profile
Time frame: 6 , 14 and 18 months
Glycemic control
Time frame: 6 , 14 and 18 months
Inflammatory state
Time frame: 6 , 14 and 18 months
Metabolomic
Time frame: 18 months
Metabolomic
Time frame: 18 months
Liver function (blood biomarkers)
Time frame: 6 and 18 months
Genetic signature
Time frame: baseline
Epigenetics
Time frame: 18 months
Epigenetics
Time frame: 18 months
Well being
Time frame: 18 months
Fecal microbiota profile
Time frame: 6, 14, 18 months
24h- continuous glucose levels
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2019.
- Derived from this study: PubMed 42227111Klein H, Alufer L, Goldberg Toren DT, Pachter D, Kamer O, Ebstein Karamani N, Chassidim Y, Shelef I, Rudich A, Yoel U, Ben-Arie G, Zelicha H, Yaskolka Meir A, Tsaban G, Bartal C, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Qi L, Stampfer MJ, Hu FB, Shai I. Lifestyle-Induced Visceral Fat Loss as a Key Target for Durable Cardiometabolic Health: MRI-Assessed 5- and 10-Year Follow-Up After 2 Clinical Trials. Circulation. 2026 Jul 7;154(1):16-27. doi: 10.1161/CIRCULATIONAHA.125.079009. Epub 2026 Jun 2.
- Derived from this study: PubMed 41888134Pachter D, Klein H, Kamer O, Goldberg Toren DT, Alufer L, Ebstein Karamani N, Atlas T, Yaary A, Hagbi I, Chassidim Y, Shelef I, Salti M, Beyer F, Witte V, Rudich A, Yoel U, Ben-Arie G, Yaskolka Meir A, Kaplan A, Tsaban G, Zelicha H, Bartal C, Qi L, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Wang DD, Stampfer MJ, Hu FB, Avidan G, Shai I. Sustained visceral fat loss is associated with attenuated brain atrophy and improved cognitive function in late midlife. Nat Commun. 2026 Mar 26;17(1):4434. doi: 10.1038/s41467-026-71141-4.
- Derived from this study: PubMed 41612310Klein H, Pachter D, Goldberg Toren DT, Kamer O, Alufer L, Ebstein Karamani N, Chassidim Y, Shelef I, Rudich A, Yoel U, Ben-Arie G, Zelicha H, Yaskolka Meir A, Tsaban G, Bartal C, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Qi L, Stampfer MJ, Hu FB, Shai I. How effective is rejoining a long-term weight loss program? The 5- and 10-year MRI-assessed Follow Interventions Trial (FIT) project. BMC Med. 2026 Jan 30;24(1):121. doi: 10.1186/s12916-026-04663-9.
- Derived from this study: PubMed 40897150Pachter D, Yaskolka Meir A, Kaplan A, Tsaban G, Zelicha H, Rinott E, Levakov G, Finkelstein O, Shelef I, Salti M, Beyer F, Witte V, Kloting N, Isermann B, Ceglarek U, Riklin Raviv T, Bluher M, Stumvoll M, Wang DD, Hu FB, Stampfer MJ, Avidan G, Shai I. Serum Galectin-9 and Decorin in relation to brain aging and the green-Mediterranean diet: A secondary analysis of the DIRECT PLUS randomized trial. Clin Nutr. 2025 Oct;53:99-108. doi: 10.1016/j.clnu.2025.08.021. Epub 2025 Aug 23.
- Derived from this study: PubMed 40472282Yaskolka Meir A, Tsaban G, Rinott E, Zelicha H, Schwarzfuchs D, Gepner Y, Rudich A, Shelef I, Bluher M, Stumvoll M, Ceglarek U, Isermann B, Kloting N, Keller M, Kovacs P, Qi L, Wang DD, Liang L, Hu FB, Stampfer MJ, Shai I. Individual response to lifestyle interventions: a pooled analysis of three long-term weight loss trials. Eur J Prev Cardiol. 2025 Nov 11;32(16):1660-1670. doi: 10.1093/eurjpc/zwaf308.
- Derived from this study: PubMed 39901232Klein H, Zelicha H, Yaskolka Meir A, Rinott E, Tsaban G, Kaplan A, Chassidim Y, Gepner Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Shelef I, Qi L, Li J, Hu FB, Stampfer MJ, Shai I. Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials. BMC Med. 2025 Feb 4;23(1):57. doi: 10.1186/s12916-025-03891-9.
- Derived from this study: PubMed 39284453Pachter D, Kaplan A, Tsaban G, Zelicha H, Meir AY, Rinott E, Levakov G, Salti M, Yovell Y, Huhn S, Beyer F, Witte V, Kovacs P, von Bergen M, Ceglarek U, Bluher M, Stumvoll M, Hu FB, Stampfer MJ, Friedman A, Shelef I, Avidan G, Shai I. Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial. Am J Clin Nutr. 2024 Nov;120(5):1029-1036. doi: 10.1016/j.ajcnut.2024.09.013. Epub 2024 Sep 14.
- Derived from this study: PubMed 38034010Alufer L, Tsaban G, Rinott E, Kaplan A, Meir AY, Zelicha H, Ceglarek U, Isermann B, Bluher M, Stumvoll M, Stampfer MJ, Shai I. Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial. Front Endocrinol (Lausanne). 2023 Nov 14;14:1243910. doi: 10.3389/fendo.2023.1243910. eCollection 2023.
- Derived from this study: PubMed 37796016Kamer O, Rinott E, Tsaban G, Kaplan A, Yaskolka Meir A, Zelicha H, Knights D, Tuohy K, Fava F, Uwe Scholz M, Ziv O, Rubin E, Bluher M, Stumvoll M, Ceglarek U, Clement K, Koren O, Hu FB, Stampfer MJ, Wang DD, Youngster I, Shai I. Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial. Gut Microbes. 2023 Dec;15(2):2264457. doi: 10.1080/19490976.2023.2264457. Epub 2023 Oct 5.
- Derived from this study: PubMed 37743489Yaskolka Meir A, Keller M, Hoffmann A, Rinott E, Tsaban G, Kaplan A, Zelicha H, Hagemann T, Ceglarek U, Isermann B, Shelef I, Bluher M, Stumvoll M, Li J, Haange SB, Engelmann B, Rolle-Kampczyk U, von Bergen M, Hu FB, Stampfer MJ, Kovacs P, Liang L, Shai I. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial. BMC Med. 2023 Sep 25;21(1):364. doi: 10.1186/s12916-023-03067-3.
- Derived from this study: PubMed 36175997Zelicha H, Kloting N, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Chassidim Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Quayson RN, von Bergen M, Engelmann B, Rolle-Kampczyk UE, Haange SB, Tuohy KM, Diotallevi C, Shelef I, Hu FB, Stampfer MJ, Shai I. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Med. 2022 Sep 30;20(1):327. doi: 10.1186/s12916-022-02525-8.
- Derived from this study: PubMed 35264213Rinott E, Meir AY, Tsaban G, Zelicha H, Kaplan A, Knights D, Tuohy K, Scholz MU, Koren O, Stampfer MJ, Wang DD, Shai I, Youngster I. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. Genome Med. 2022 Mar 10;14(1):29. doi: 10.1186/s13073-022-01015-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iris Shai, PhD principal investigator
Ben-Gurion University of the Negev
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Physical activity, Physical activity+ MED diet and Physical activity+green MED diet in people with Abdominal Obesity Metabolic Syndrome, run by Ben-Gurion University of the Negev at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abdominal fat (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03020186, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2019.