The Effect of Mankai on Glycemic Control Among Patients With T2D

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Effect of Wolffia Globosa (Mankai) on Glycemic Control Among Patients With Type 2 Diabetes; A 3-month Randomized Controlled Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06416475
• Other study ID #: SOR-0259-23
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 30, 2024
• Est. completion date: August 15, 2024

Study information

• Verified date: May 2024
• Source: Ben-Gurion University of the Negev
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 104
• Est. completion date: August 15, 2024
• Est. primary completion date: August 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Regular Mankai consumption

• State of pregnancy or lactation

• Presence of active cancer or chemotherapy treatment in last three years

• Participation in another trial

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Dietary Supplement:
• Mankai supplementation
The overall dose of the three Mankai duckweed beverages/day contains ~10 grams of dry matter.

Other:
• Water consumption
Water consumption

Locations

Country	Name	City	State
Israel	Soroka Medical Center	Be'er Sheva

Sponsors (2)

Lead Sponsor	Collaborator
Ben-Gurion University of the Negev	Soroka University Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (19)

Corrigendum 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. — View Citation

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Joseph 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. — View Citation

Kaplan 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. — View Citation

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. Erratum In: Circ Res. 2020 Jul 17;127(3):e107. — View Citation

Rinott 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. — View Citation

Rinott E, Youngster I, Yaskolka Meir A, Tsaban G, Zelicha H, Kaplan A, Knights D, Tuohy K, Fava F, Scholz MU, Ziv O, Rubin E, Tirosh A, Rudich A, Bluher M, Stumvoll M, Ceglarek U, Clement K, Koren O, Wang DD, Hu FB, Stampfer MJ, Shai I. Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain. Gastroenterology. 2021 Jan;160(1):158-173.e10. doi: 10.1053/j.gastro.2020.08.041. Epub 2020 Aug 26. — View Citation

Sela 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. — View Citation

Tsaban 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. — View Citation

Tsaban 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. — View Citation

Tsaban 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. — View Citation

Yancy 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. — View Citation

Yaskolka 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. — View Citation

Yaskolka 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. — View Citation

Yaskolka 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. — View Citation

Zelicha H, Kaplan A, Yaskolka Meir A, Tsaban G, Rinott E, Shelef I, Tirosh A, Brikner D, Pupkin E, Qi L, Thiery J, Stumvoll M, Kloting N, von Bergen M, Ceglarek U, Bluher M, Stampfer MJ, Shai I. The Effect of Wolffia globosa Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial. Diabetes Care. 2019 Jul;42(7):1162-1169. doi: 10.2337/dc18-2319. Epub 2019 May 10. — View Citation

Zelicha 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. — View Citation

Zhu 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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	Glycated hemoglobin-HbA1c; as detected by a standard laboratory measure	Baseline and three months time points
Primary	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]	Baseline and three months time points
Secondary	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)	Baseline and three months time points
Secondary	Lipid profile	Changes in lipid biomarkers (blood draw), such as apo(A)1(g/L), apo(B)100 (g/L)	Baseline and three months time points
Secondary	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)	Baseline and three months time points
Secondary	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)	Baseline and three months time points
Secondary	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)]	Baseline and three months time points
Secondary	CVD biomarkers	Changes in CVD biomarkers (blood draw); such as Homocysteine (ug/dL)	Baseline and three months time points
Secondary	CVD biomarkers	Changes in CVD biomarkers (blood draw); such as Renin (iU/ml)	Baseline and three months time points
Secondary	CVD biomarkers	Changes in CVD biomarkers (blood draw); such as Troponin (cardiac troponin I and T) (ng/ml)	Baseline and three months time points
Secondary	CVD biomarkers	Changes in CVD biomarkers (blood draw); such as NT-pro-BNP (pg/ml)	Baseline and three months time points
Secondary	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)	Baseline and three months time points
Secondary	Cardiometabolic health-Liver function (blood biomarkers)	Changes in liver function biomarkers (blood draw); such as bilirubin (mg/dL)	Baseline and three months time points
Secondary	HPA axis biomarkers	Changes in HPA axis biomarkers (blood draw); such as ACTH (pmol/L)	Baseline and three months time points
Secondary	HPA axis biomarkers	Changes in HPA axis biomarkers (blood draw); such as cortisol (nmol/L)	Baseline and three months time points
Secondary	HPA axis biomarkers	Changes in HPA axis biomarkers (blood draw); such as cortisone (microg/L)	Baseline and three months time points
Secondary	HPG axis biomarkers	Changes in HPG axis; such as Testosterone (nmol/L), SHBG (nmol/L), IGF1 (nmol/L)	Baseline and three months time points
Secondary	HPG axis biomarkers	Changes in HPG axis; such as LH (IU/mL)	Baseline and three months time points
Secondary	HPG axis biomarkers	Changes in HPG axis; such as FSH (IU/L)	Baseline and three months time points
Secondary	HPG axis biomarkers	Changes in HPG axis; such as GH (pmol/L)	Baseline and three months time points
Secondary	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.	Baseline and three months time points
Secondary	Microbiota profiling	Shannon Diversity Index (where 0 indicates no diversity, there is no upper limit to the index, usually between 1.5 - 3.5).	Baseline and three months time points
Secondary	Weight	Bodyweight will be measured without shoes to the nearest 0.1 kg.	Baseline and three months time points
Secondary	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.	Baseline and three months time points
Secondary	BMI	Weight and Height will be combined to report BMI in kg/m^2	Baseline and three months time points
Secondary	Blood pressure	Blood pressure will be measured and determined using an automated system in mmHg. Both systolic and diastolic blood pressure will be measured.	Baseline and three months time points
Secondary	Resting pulse	Pulse will be measured and determined using an automated system in Beats per minute.	Baseline and three months time points
Secondary	Urine biomarkers	Urine albumin (mg/dL)	Baseline and three months time points
Secondary	Urine biomarkers	UACR (mg/g)	Baseline and three months time points
Secondary	Urine biomarkers	Urine creatinine (g/dL)	Baseline and three months time points
Secondary	Urine biomarkers	eGFR (ml/min/1.73m^2)	Baseline and three months time points
Secondary	Urine biomarkers	Urine polyphenols for adherence as measured by mass spectrometry.	Baseline and three months time points