Diabetes Mellitus, Type 2Phase 2NCT06416475
The Effect of Mankai on Glycemic Control Among Patients With T2D
A Phase 2 study testing Mankai supplementation and Water consumption in people with Diabetes Mellitus, Type 2, run by Ben-Gurion University of the Negev at 1 site in Israel.
Trial summary
The investigators aim to explore the effect of daily supplementation of Wolfia globosa Mankai on HbA1c and insulin resistance response among participants with type 2 diabetes (T2D). The investigators hypothesize that adding daily Mankai to T2D's healthy nutrition might lower HbA1c and promote glycemic control. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Mankai supplementation and Water consumption
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteIsrael
- Study dates
- 30 Apr 2024to 15 Aug 2024
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 30 years
- A formal diagnosis of T2D (126mg/dl fasting glucose or higher, or HbA1c>6.5%) or taking T2D medications with HbA1c levels over 7%
- Medication stability for at least 3 months prior to Intervention initiation
- Adherence to medical follow-up in primary care clinic or diabetes-centered outpatient services
Who cannot join
- HbA1c lower than 7% or higher than 10%
- Known insulinopenia
- Treatment with coumadin (warfarin)
- Advanced renal failure
- Significantly disturbed liver enzymes (liver transaminases or bilirubin levels more than time three upper-normal-limit)
- A significant illness that might require hospitalization
Show all 10Show fewer
- Regular Mankai consumption
- State of pregnancy or lactation
- Presence of active cancer or chemotherapy treatment in last three years
- Participation in another trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Wolffia Globosa (Mankai) on Glycemic Control Among Patients With Type 2 Diabetes; A 3-month Randomized Controlled Pilot Trial
The investigators aim to explore the effect of daily supplementation of Wolfia globosa Mankai on HbA1c and insulin resistance response among participants with type 2 diabetes (T2D). The investigators hypothesize that adding daily Mankai to T2D's healthy nutrition might lower HbA1c and promote glycemic control.
Methods: A 3-month pilot RCT among 104 patients with T2D, with two intervention arms consuming comparable bottle volumes of either crude plant Mankai beverage (60ml Mankai) or water (60ml) 3 times/day postprandially over 3 months. Blood, urine, fecal, and clinical measures will be taken at 0 and 3 months. Overall appetite, food intake, symptoms, and medical treatment will be monitored.
Importance: This study's results will shed light on the effects of regular Mankai consumption on HbA1c among patients with T2D, which may reveal a new nutritional source to improve glycemic control in T2D.
Read the detailed description
Type 2 diabetes (T2D), most commonly stemming from sustained obesity, adiposity, and a sedentary lifestyle, is strongly associated with increased cardiovascular risk. Glycated hemoglobin A1c (HbA1c), reflecting glycemic control, is tightly related to cardiovascular risk. In the recent decade, several antihyperglycemic medications have been shown to modify cardiovascular risk among patients with established cardiovascular disease. Maintaining a healthy diet, preferably a Mediterranean-like diet, rich in plant-based protein and low in meat products, is the first-line intervention to promote glycemic control and reduce cardiovascular risk among T2D. However, whether specific nutritional products may independently promote glycemic control beyond medical treatment is unclear.
Mankai, a newly cultivated duckweed Wolffia-globosa strain, has been extensively studied in recent years. Mankai is rich in whole bioavailable protein, iron, and vitamin B12 and is rich in 200 different potent polyphenols, potentially affecting the metabolomic-gut-clinical axis. Mankai consumption, as a dominant part of the green-Mediterranean diet, was shown to promote weight loss, systemic inflammation lowering, and cardiometabolic risk reduction and was associated with regressions in hepatosteatosis, visceral abdominal adiposity, and proximal aortic stiffness among patients with abdominal obesity with or without T2D. Also, Mankai consumption was mainly linked with improved glycemic control, dramatic elevation in fasting Ghrelin levels, and insulin sensitivity recovery. Regular Mankai consumption promoted microbiome optimization, mainly impacting bacterial glucose metabolism and human glucose control.
In this proposed study, The investigators aim to explore the effect of daily consumption of 60mL crude plant Mankai beverage boost after 3 meals among patients with T2D on HbA1c levels (gold-standard for assessing glycemic control, primary outcome).
"Mankai" is a cultivated strain of Wolffia globosa, an aquatic plant, part of the family of plants known commonly as duckweeds. Duckweeds are elementary flowering aquatic plants floating on or beneath still or slow-moving water bodies.
There is a long history of using Wolffia species, particularly 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 plant is cultivated locally in rain-fed open ponds, grown commercially in Thailand, and sold in local markets throughout Thailand and Laos. There are numerous ways of Wolffia globosa consumption and a variety of recipes, using it either as the main ingredient (such as Wolffia crisps or "Kaeng pum" - a popular vegetable dish in northeastern Thailand) or incorporating it in other foods (e.g., Wolffia-meat ball, fermented Wolffia-meat sausage, Wolffia rice noodle, Wolffia cookies, Wolffia bread, and various soups and salads). Moreover, Wolffia is known as one of the essential food sources in northern Thailand.
Along with its long history as a food source in Southeast Asia, it is recognized as an edible vegetable for humans in several databases, including the USDA (2014) GRIN database and a database dedicated to tropical species. For the proposed clinical trial, Mankai will be provided as a beverage, refrigerated at ±4°C. Participants will consume Mankai as an additional additive to a standardized healthy Mediterranean diet.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Mankai supplementation, Water consumption
- Keywords
- clinical trial, Diabetes Mellitus, Type 2, nutritional intervention, Mankai Duckweed, Wolffia-globosa, polyphenols
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mankai supplementationDietary supplement
The overall dose of the three Mankai duckweed beverages/day contains ~10 grams of dry matter.
Water consumptionOther
Water consumption
| Study group | Role | What they receive |
|---|---|---|
| Mankai supplementation group | Active comparator | Three times a day supplementation of postprandial Mankai duckweed drink (60mL crude plant Mankai beverage) right after breakfast, lunch, and dinner while maintaining the recommended Mediterranean diet lifestyle and medical treatment. Receives: Dietary Supplement: Mankai supplementation |
| Water group | Placebo comparator | Three times a day consumption of postprandial water (60mL) right after breakfast, lunch, and dinner while maintaining the recommended Mediterranean diet lifestyle and medical treatment. Receives: Other: Water consumption |
What is being measured
The primary outcome is the main question the study is designed to answer.
HbA1c
Glycated hemoglobin-HbA1c; as detected by a standard laboratory measure
Measured: Baseline and three months time points
Fasting glycemic and insulin resistance profiling
Fasting glycemic and insulin resistance profiling [using calculated homeostatic model assessment of insulin resistance (HOMA-IR) as detected by laboratory assessment]
Measured: Baseline and three months time points
Secondary outcomes (30)
Lipid profile
Changes in lipid biomarkers (blood draw), such as LDL (mg/dL), HDL (mg/dL), TG (mg/dL), total cholesterol (mg/dL), Lipoprotein (a) (mg/dL)
Measured: Baseline and three months time points
Lipid profile
Changes in lipid biomarkers (blood draw), such as apo(A)1(g/L), apo(B)100 (g/L)
Measured: Baseline and three months time points
Hormones and adipokines
Changes in hormone and adipokine biomarkers (blood draw); such as total adiponectin (ug/ml), RBP4 (ug/ml), chemerin (ng/ml), vaspin (ng/ml), omentin-1(ng/ml), MCP-1 (pg/ml)
Measured: Baseline and three months time points
Inflammatory biomarkers
Changes in inflammatory biomarkers (blood draw); such as CRP (mg/dl), IL-1 (pg/mL), IL-6 (pg/mL), IL10 (pg/mL), IL-17 (pg/mL), TNF-alpha (pg/mL)
Measured: Baseline and three months time points
Hunger/satiety hormones
Changes in Hunger/satiety hormones (blood draw); such as leptin(ng/ml), ghrelin(pg/ml), neuropeptide Y (NPY) (pg/ml), cholecystokinin (CCK) (pmol/L), peptide YY (PYY) (pmol/L), and incretins (e.g., oxyntomodulin (pmol/L) and glucagon-like peptide-1 (GLP-1)(pmol/L)]
Measured: Baseline and three months time points
CVD biomarkers
Changes in CVD biomarkers (blood draw); such as Homocysteine (ug/dL)
Measured: Baseline and three months time points
CVD biomarkers
Changes in CVD biomarkers (blood draw); such as Renin (iU/ml)
Measured: Baseline and three months time points
CVD biomarkers
Changes in CVD biomarkers (blood draw); such as Troponin (cardiac troponin I and T) (ng/ml)
Measured: Baseline and three months time points
CVD biomarkers
Changes in CVD biomarkers (blood draw); such as NT-pro-BNP (pg/ml)
Measured: Baseline and three months time points
Cardiometabolic health-Liver function (blood biomarkers)
Changes in liver function biomarkers (blood draw); such as Alkaline Phosphatase (U/L), Alanine Aminotransferase (U/L), Aspartate Aminotransferase (U/L), bilirubin (mg/dL)
Measured: Baseline and three months time points
Cardiometabolic health-Liver function (blood biomarkers)
Changes in liver function biomarkers (blood draw); such as bilirubin (mg/dL)
Measured: Baseline and three months time points
HPA axis biomarkers
Changes in HPA axis biomarkers (blood draw); such as ACTH (pmol/L)
Measured: Baseline and three months time points
HPA axis biomarkers
Changes in HPA axis biomarkers (blood draw); such as cortisol (nmol/L)
Measured: Baseline and three months time points
HPA axis biomarkers
Changes in HPA axis biomarkers (blood draw); such as cortisone (microg/L)
Measured: Baseline and three months time points
HPG axis biomarkers
Changes in HPG axis; such as Testosterone (nmol/L), SHBG (nmol/L), IGF1 (nmol/L)
Measured: Baseline and three months time points
HPG axis biomarkers
Changes in HPG axis; such as LH (IU/mL)
Measured: Baseline and three months time points
HPG axis biomarkers
Changes in HPG axis; such as FSH (IU/L)
Measured: Baseline and three months time points
HPG axis biomarkers
Changes in HPG axis; such as GH (pmol/L)
Measured: Baseline and three months time points
Well being
Assessed by questionnaires; 1. Screening questionnaire 2. I-MEDAS (Mediterranean Diet Adherence Screener) questionnaire - the 14-item MEDAS questionnaire (scale 0-17, higher score indicated higher adherence to Mediterranean diets), 3. Validated physical activity questionnaire, 4. Symptoms questionnaire, 5. Medical questionnaire, and 6. A follow-up questionnaire.
Measured: Baseline and three months time points
Microbiota profiling
Shannon Diversity Index (where 0 indicates no diversity, there is no upper limit to the index, usually between 1.5 - 3.5).
Measured: Baseline and three months time points
Weight
Bodyweight will be measured without shoes to the nearest 0.1 kg.
Measured: Baseline and three months time points
Waist circumference
WC will be measured halfway between the last rib and the iliac crest to the nearest millimeter by standard procedures using a 150-cm anthropometric measuring tape.
Measured: Baseline and three months time points
BMI
Weight and Height will be combined to report BMI in kg/m^2
Measured: Baseline and three months time points
Blood pressure
Blood pressure will be measured and determined using an automated system in mmHg. Both systolic and diastolic blood pressure will be measured.
Measured: Baseline and three months time points
Resting pulse
Pulse will be measured and determined using an automated system in Beats per minute.
Measured: Baseline and three months time points
Urine biomarkers
Urine albumin (mg/dL)
Measured: Baseline and three months time points
Urine biomarkers
UACR (mg/g)
Measured: Baseline and three months time points
Urine biomarkers
Urine creatinine (g/dL)
Measured: Baseline and three months time points
Urine biomarkers
eGFR (ml/min/1.73m^2)
Measured: Baseline and three months time points
Urine biomarkers
Urine polyphenols for adherence as measured by mass spectrometry.
Measured: Baseline and three months time points
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start30 Apr 2024
- Primary completion8 Aug 2024 (estimated)
- Study completion15 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A 3-month Randomized Controlled pilot Trial among 104 patients with T2D, who will be randomly allocated to consume comparable bottle volumes of either crude plant Mankai beverage (60ml Mankai) or water (60ml) on top of a standardized MediterraneanT2D-recommended healthy diet, after morning, lunch, and dinner over 3 months.
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ben-Gurion University of the Negev
- Sponsor type
- University, hospital or other
- Collaborators
- Soroka University Medical Center
- Responsible party
- Principal investigator, Iris Shai, Ben-Gurion University of the Negev
- Investigators
- Idit Liberty, Principal investigator, Soroka University Medical CenterIris Shai, Study director, Ben-Gurion University of the Negev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06416475
- Sponsor's protocol ID
- SOR-0259-23
- Status last verified
- May 2024
- First submitted
- 21 Mar 2024
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Piche ME, Tchernof A, Despres JP. Obesity Phenotypes, Diabetes, and Cardiovascular Diseases. Circ Res. 2020 May 22;126(11):1477-1500. doi: 10.1161/CIRCRESAHA.120.316101. Epub 2020 May 21.
PubMed 32437302Joseph JJ, Deedwania P, Acharya T, Aguilar D, Bhatt DL, Chyun DA, Di Palo KE, Golden SH, Sperling LS; American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; and Council on Hypertension. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. 2022 Mar;145(9):e722-e759. doi: 10.1161/CIR.0000000000001040. Epub 2022 Jan 10.
PubMed 35000404Zhu J, Yu X, Zheng Y, Li J, Wang Y, Lin Y, He Z, Zhao W, Chen C, Qiu K, Wu J. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol. 2020 Mar;8(3):192-205. doi: 10.1016/S2213-8587(19)30422-X. Epub 2020 Jan 29.
PubMed 32006518Yancy WS Jr, Dunbar SA, Boucher JL, Cypress M, Evert AB, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Urbanski P, Verdi CL, Nwankwo R. Response to comments on Evert et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes care 2013;36:3821-3842. Diabetes Care. 2014 May;37(5):e102-3. doi: 10.2337/dc14-0077. No abstract available.
PubMed 24757235Corrigendum to: 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J. 2022 Nov 7;43(42):4468. doi: 10.1093/eurheartj/ehac458. No abstract available.
PubMed 36083202Kaplan A, Zelicha H, Tsaban G, Yaskolka Meir A, Rinott E, Kovsan J, Novack L, Thiery J, Ceglarek U, Burkhardt R, Willenberg A, Tirosh A, Cabantchik I, Stampfer MJ, Shai I. Protein bioavailability of Wolffia globosa duckweed, a novel aquatic plant - A randomized controlled trial. Clin Nutr. 2019 Dec;38(6):2576-2582. doi: 10.1016/j.clnu.2018.12.009. Epub 2018 Dec 11.
PubMed 30591380Yaskolka Meir A, Tsaban G, Zelicha H, Rinott E, Kaplan A, Youngster I, Rudich A, Shelef I, Tirosh A, Brikner D, Pupkin E, Sarusi B, Bluher M, Stumvoll M, Thiery J, Ceglarek U, Stampfer MJ, Shai I. A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats. J Nutr. 2019 Jun 1;149(6):1004-1011. doi: 10.1093/jn/nxy321.
PubMed 30915471Sela I, Yaskolka Meir A, Brandis A, Krajmalnik-Brown R, Zeibich L, Chang D, Dirks B, Tsaban G, Kaplan A, Rinott E, Zelicha H, Arinos S, Ceglarek U, Isermann B, Lapidot M, Green R, Shai I. Wolffia globosa-Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans. Nutrients. 2020 Oct 8;12(10):3067. doi: 10.3390/nu12103067.
PubMed 33049929Yaskolka Meir A, Tuohy K, von Bergen M, Krajmalnik-Brown R, Heinig U, Zelicha H, Tsaban G, Rinott E, Kaplan A, Aharoni A, Zeibich L, Chang D, Dirks B, Diotallevi C, Arapitsas P, Vrhovsek U, Ceglarek U, Haange SB, Rolle-Kampczyk U, Engelmann B, Lapidot M, Colt M, Sun Q, Shai I. The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols. Nutrients. 2021 May 30;13(6):1866. doi: 10.3390/nu13061866.
PubMed 34070816Tsaban G, Yaskolka Meir A, Rinott E, Zelicha H, Kaplan A, Shalev A, Katz A, Rudich A, Tirosh A, Shelef I, Youngster I, Lebovitz S, Israeli N, Shabat M, Brikner D, Pupkin E, Stumvoll M, Thiery J, Ceglarek U, Heiker JT, Korner A, Landgraf K, von Bergen M, Bluher M, Stampfer MJ, Shai I. The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. 2021 Jun 11;107(13):1054-1061. doi: 10.1136/heartjnl-2020-317802.
PubMed 33234670Yaskolka 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 33461965Zelicha 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 36175997Tsaban G, Shalev A, Katz A, Yaskolka Meir A, Rinott E, Zelicha H, Kaplan A, Wolak A, Bluher M, Stampfer MJ, Shai I. Effect of Lifestyle Modification and Green Mediterranean Diet on Proximal Aortic Stiffness. J Am Coll Cardiol. 2023 Apr 25;81(16):1659-1661. doi: 10.1016/j.jacc.2023.02.032. No abstract available.
PubMed 37076220Tsaban 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 34643713Rinott 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 35264213
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Wolffia Globosa (Mankai) on Glycemic Control Among Patients With Type 2 Diabetes; A 3-month Randomized Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT06416475
- Acronym / sponsor ID
- SOR-0259-23
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- clinical trial, Diabetes Mellitus, Type 2, nutritional intervention, Mankai Duckweed, Wolffia-globosa, polyphenols
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Ben-Gurion University of the NegevUniversity, hospital or other
- Collaborators
- Soroka University Medical Center
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- 8 Aug 2024 (estimated)
- Study completion
- 15 Aug 2024 (estimated)
- First posted
- 16 May 2024 (actual)
- 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.
The investigators aim to explore the effect of daily supplementation of Wolfia globosa Mankai on HbA1c and insulin resistance response among participants with type 2 diabetes (T2D). The investigators hypothesize that adding daily Mankai to T2D's healthy nutrition might lower HbA1c and promote glycemic control.
Methods: A 3-month pilot RCT among 104 patients with T2D, with two intervention arms consuming comparable bottle volumes of either crude plant Mankai beverage (60ml Mankai) or water (60ml) 3 times/day postprandially over 3 months. Blood, urine, fecal, and clinical measures will be taken at 0 and 3 months. Overall appetite, food intake, symptoms, and medical treatment will be monitored.
Importance: This study's results will shed light on the effects of regular Mankai consumption on HbA1c among patients with T2D, which may reveal a new nutritional source to improve glycemic control in T2D.
Detailed description
Type 2 diabetes (T2D), most commonly stemming from sustained obesity, adiposity, and a sedentary lifestyle, is strongly associated with increased cardiovascular risk. Glycated hemoglobin A1c (HbA1c), reflecting glycemic control, is tightly related to cardiovascular risk. In the recent decade, several antihyperglycemic medications have been shown to modify cardiovascular risk among patients with established cardiovascular disease. Maintaining a healthy diet, preferably a Mediterranean-like diet, rich in plant-based protein and low in meat products, is the first-line intervention to promote glycemic control and reduce cardiovascular risk among T2D. However, whether specific nutritional products may independently promote glycemic control beyond medical treatment is unclear.
Mankai, a newly cultivated duckweed Wolffia-globosa strain, has been extensively studied in recent years. Mankai is rich in whole bioavailable protein, iron, and vitamin B12 and is rich in 200 different potent polyphenols, potentially affecting the metabolomic-gut-clinical axis. Mankai consumption, as a dominant part of the green-Mediterranean diet, was shown to promote weight loss, systemic inflammation lowering, and cardiometabolic risk reduction and was associated with regressions in hepatosteatosis, visceral abdominal adiposity, and proximal aortic stiffness among patients with abdominal obesity with or without T2D. Also, Mankai consumption was mainly linked with improved glycemic control, dramatic elevation in fasting Ghrelin levels, and insulin sensitivity recovery. Regular Mankai consumption promoted microbiome optimization, mainly impacting bacterial glucose metabolism and human glucose control.
In this proposed study, The investigators aim to explore the effect of daily consumption of 60mL crude plant Mankai beverage boost after 3 meals among patients with T2D on HbA1c levels (gold-standard for assessing glycemic control, primary outcome).
"Mankai" is a cultivated strain of Wolffia globosa, an aquatic plant, part of the family of plants known commonly as duckweeds. Duckweeds are elementary flowering aquatic plants floating on or beneath still or slow-moving water bodies.
There is a long history of using Wolffia species, particularly 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 plant is cultivated locally in rain-fed open ponds, grown commercially in Thailand, and sold in local markets throughout Thailand and Laos. There are numerous ways of Wolffia globosa consumption and a variety of recipes, using it either as the main ingredient (such as Wolffia crisps or "Kaeng pum" - a popular vegetable dish in northeastern Thailand) or incorporating it in other foods (e.g., Wolffia-meat ball, fermented Wolffia-meat sausage, Wolffia rice noodle, Wolffia cookies, Wolffia bread, and various soups and salads). Moreover, Wolffia is known as one of the essential food sources in northern Thailand.
Along with its long history as a food source in Southeast Asia, it is recognized as an edible vegetable for humans in several databases, including the USDA (2014) GRIN database and a database dedicated to tropical species. For the proposed clinical trial, Mankai will be provided as a beverage, refrigerated at ±4°C. Participants will consume Mankai as an additional additive to a standardized healthy Mediterranean diet.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A 3-month Randomized Controlled pilot Trial among 104 patients with T2D, who will be randomly allocated to consume comparable bottle volumes of either crude plant Mankai beverage (60ml Mankai) or water (60ml) on top of a standardized MediterraneanT2D-recommended healthy diet, after morning, lunch, and dinner over 3 months.
| Arm | Type | Receives |
|---|---|---|
| Mankai supplementation group | Active comparator | Dietary Supplement: Mankai supplementationThree times a day supplementation of postprandial Mankai duckweed drink (60mL crude plant Mankai beverage) right after breakfast, lunch, and dinner while maintaining the recommended Mediterranean diet lifestyle and medical treatment. |
| Water group | Placebo comparator | Other: Water consumptionThree times a day consumption of postprandial water (60mL) right after breakfast, lunch, and dinner while maintaining the recommended Mediterranean diet lifestyle and medical treatment. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 30 years
- A formal diagnosis of T2D (126mg/dl fasting glucose or higher, or HbA1c>6.5%) or taking T2D medications with HbA1c levels over 7%
- Medication stability for at least 3 months prior to Intervention initiation
- Adherence to medical follow-up in primary care clinic or diabetes-centered outpatient services
Key exclusion criteria (10 listed)
- HbA1c lower than 7% or higher than 10%
- Known insulinopenia
- Treatment with coumadin (warfarin)
- Advanced renal failure
- Significantly disturbed liver enzymes (liver transaminases or bilirubin levels more than time three upper-normal-limit)
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 |
|---|---|---|
| Mankai supplementationThe overall dose of the three Mankai duckweed beverages/day contains ~10 grams of dry matter. | Dietary supplement | Mankai supplementation group |
| Water consumptionWater consumption | Other | Water group |
Primary outcome
HbA1c
Time frame: Baseline and three months time points
Glycated hemoglobin-HbA1c; as detected by a standard laboratory measure
Fasting glycemic and insulin resistance profiling
Time frame: Baseline and three months time points
Fasting glycemic and insulin resistance profiling [using calculated homeostatic model assessment of insulin resistance (HOMA-IR) as detected by laboratory assessment]
30 secondary outcomes
Lipid profile
Time frame: Baseline and three months time points
Lipid profile
Time frame: Baseline and three months time points
Hormones and adipokines
Time frame: Baseline and three months time points
Inflammatory biomarkers
Time frame: Baseline and three months time points
Hunger/satiety hormones
Time frame: Baseline and three months time points
CVD biomarkers
Time frame: Baseline and three months time points
CVD biomarkers
Time frame: Baseline and three months time points
CVD biomarkers
Time frame: Baseline and three months time points
CVD biomarkers
Time frame: Baseline and three months time points
Cardiometabolic health-Liver function (blood biomarkers)
Time frame: Baseline and three months time points
Cardiometabolic health-Liver function (blood biomarkers)
Time frame: Baseline and three months time points
HPA axis biomarkers
Time frame: Baseline and three months time points
HPA axis biomarkers
Time frame: Baseline and three months time points
HPA axis biomarkers
Time frame: Baseline and three months time points
HPG axis biomarkers
Time frame: Baseline and three months time points
HPG axis biomarkers
Time frame: Baseline and three months time points
HPG axis biomarkers
Time frame: Baseline and three months time points
HPG axis biomarkers
Time frame: Baseline and three months time points
Well being
Time frame: Baseline and three months time points
Microbiota profiling
Time frame: Baseline and three months time points
Weight
Time frame: Baseline and three months time points
Waist circumference
Time frame: Baseline and three months time points
BMI
Time frame: Baseline and three months time points
Blood pressure
Time frame: Baseline and three months time points
Resting pulse
Time frame: Baseline and three months time points
Urine biomarkers
Time frame: Baseline and three months time points
Urine biomarkers
Time frame: Baseline and three months time points
Urine biomarkers
Time frame: Baseline and three months time points
Urine biomarkers
Time frame: Baseline and three months time points
Urine biomarkers
Time frame: Baseline and three months time points
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Background: PubMed 32437302Piche ME, Tchernof A, Despres JP. Obesity Phenotypes, Diabetes, and Cardiovascular Diseases. Circ Res. 2020 May 22;126(11):1477-1500. doi: 10.1161/CIRCRESAHA.120.316101. Epub 2020 May 21.
- Background: PubMed 35000404Joseph JJ, Deedwania P, Acharya T, Aguilar D, Bhatt DL, Chyun DA, Di Palo KE, Golden SH, Sperling LS; American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; and Council on Hypertension. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. 2022 Mar;145(9):e722-e759. doi: 10.1161/CIR.0000000000001040. Epub 2022 Jan 10.
- Background: PubMed 32006518Zhu J, Yu X, Zheng Y, Li J, Wang Y, Lin Y, He Z, Zhao W, Chen C, Qiu K, Wu J. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol. 2020 Mar;8(3):192-205. doi: 10.1016/S2213-8587(19)30422-X. Epub 2020 Jan 29.
- Background: PubMed 24757235Yancy WS Jr, Dunbar SA, Boucher JL, Cypress M, Evert AB, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Urbanski P, Verdi CL, Nwankwo R. Response to comments on Evert et al. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes care 2013;36:3821-3842. Diabetes Care. 2014 May;37(5):e102-3. doi: 10.2337/dc14-0077. No abstract available.
- Background: PubMed 36083202Corrigendum to: 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J. 2022 Nov 7;43(42):4468. doi: 10.1093/eurheartj/ehac458. No abstract available.
- Background: PubMed 30591380Kaplan A, Zelicha H, Tsaban G, Yaskolka Meir A, Rinott E, Kovsan J, Novack L, Thiery J, Ceglarek U, Burkhardt R, Willenberg A, Tirosh A, Cabantchik I, Stampfer MJ, Shai I. Protein bioavailability of Wolffia globosa duckweed, a novel aquatic plant - A randomized controlled trial. Clin Nutr. 2019 Dec;38(6):2576-2582. doi: 10.1016/j.clnu.2018.12.009. Epub 2018 Dec 11.
- Background: PubMed 30915471Yaskolka Meir A, Tsaban G, Zelicha H, Rinott E, Kaplan A, Youngster I, Rudich A, Shelef I, Tirosh A, Brikner D, Pupkin E, Sarusi B, Bluher M, Stumvoll M, Thiery J, Ceglarek U, Stampfer MJ, Shai I. A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats. J Nutr. 2019 Jun 1;149(6):1004-1011. doi: 10.1093/jn/nxy321.
- Background: PubMed 33049929Sela I, Yaskolka Meir A, Brandis A, Krajmalnik-Brown R, Zeibich L, Chang D, Dirks B, Tsaban G, Kaplan A, Rinott E, Zelicha H, Arinos S, Ceglarek U, Isermann B, Lapidot M, Green R, Shai I. Wolffia globosa-Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans. Nutrients. 2020 Oct 8;12(10):3067. doi: 10.3390/nu12103067.
- Background: PubMed 34070816Yaskolka Meir A, Tuohy K, von Bergen M, Krajmalnik-Brown R, Heinig U, Zelicha H, Tsaban G, Rinott E, Kaplan A, Aharoni A, Zeibich L, Chang D, Dirks B, Diotallevi C, Arapitsas P, Vrhovsek U, Ceglarek U, Haange SB, Rolle-Kampczyk U, Engelmann B, Lapidot M, Colt M, Sun Q, Shai I. The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols. Nutrients. 2021 May 30;13(6):1866. doi: 10.3390/nu13061866.
- Background: PubMed 33234670Tsaban G, Yaskolka Meir A, Rinott E, Zelicha H, Kaplan A, Shalev A, Katz A, Rudich A, Tirosh A, Shelef I, Youngster I, Lebovitz S, Israeli N, Shabat M, Brikner D, Pupkin E, Stumvoll M, Thiery J, Ceglarek U, Heiker JT, Korner A, Landgraf K, von Bergen M, Bluher M, Stampfer MJ, Shai I. The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. 2021 Jun 11;107(13):1054-1061. doi: 10.1136/heartjnl-2020-317802.
- Background: PubMed 33461965Yaskolka 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.
- Background: 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.
- Individual participant dataSharing planned: No
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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.
Idit Liberty principal investigator
Soroka University Medical Center
Iris Shai study director
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 Phase 2 study testing Mankai supplementation and Water consumption in people with Diabetes Mellitus, Type 2, 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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 16 May 2024. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
HbA1c (time frame: Baseline and three months time points). The study lists 2 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 NCT06416475, which also lists 19 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 16 May 2024.