Effects of Tocotrienols Supplementation on Platelet Aggregation in Subjects With Metabolic Syndrome

Study Overview
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Brief Summary
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The objective of this study is to address the anti-thrombotic effects of tocotrienols supplementation via modulation of platelet activation, thrombotic markers, inflammatory markers and endothelial function. It is hypothesized that 2 weeks supplementation of tocotrienols will be able to suppress platelet aggregation in subjects with metabolic syndrome.

Detailed Description
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A double-blind, randomized, crossover study comparing the effects of tocotrienols vs. placebo will be conducted in subjects with metabolic syndrome. Subjects will be supplemented with Tocovid Suprabio 200 mg twice daily (or placebo) for 2 weeks followed by a postprandial challenge on Day 14. During the postprandial challenge, venous blood samples will be collected during fasting. Subjects are then required to consume a high fat breakfast meal containing 50g fat and 100mL milkshake, followed by the assigned capsules. Venous blood samples will be drawn at 2, 4 and 6 hours after consumption of capsules. A washout period of at least 14 days will be in place before the commencement of the second treatment.

Official Title
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Effects of Tocotrienols Supplementation on Platelet Aggregation in Subjects With Metabolic Syndrome

Conditions
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Metabolic Syndrome, Platelet Aggregation, Spontaneous

Intervention / Treatment
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* Dietary Supplement: Tocotrienol-rich fraction 400mg
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-60 year Haemoglobin level >11.5 g/dL in women and >12.5 g/dL in men Serum ferritin > 15µg/L According to Clinical Practice Guidelines, Management of Type 2 Diabetes Mellitus in Malaysia (2009), metabolic syndrome subjects are identified with: Waist circumference ≥ 90 cm in men and ≥ 80 cm in women and with any two of the following criteria: Elevated triacylglycerols > 1.7 mmol/L Low HDL cholesterol < 1.0 mmol/L in men and < 1.3 mmol/L in women Elevated blood pressure ≥ 130/≥85 mm Hg Fasting glucose ≥ 5.6 mmol/L to 7 mmol/L Exclusion Criteria: Medical history of myocardial infarction, angina, ischemic attack, hemorrhagic stroke, deep vein thrombosis, coronary artery disease, bleeding disorder, cancer, allergy to vitamin E Smoker Lactose intolerance Pregnancy or lactation Current use of vitamin E, medications modulating blood coagulation, hypertension, lipid-lowering and glucose-lowering agents, corticosteroids Significant hepatic and renal impairment Fever, cold or infection during bleeding day Alcoholic

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocotrienol-rich fraction 400mg<br> | Dietary Supplement: Tocotrienol-rich fraction 400mg<br>* Tocovid Suprabio 200mg is taken twice daily (after breakfast and dinner) for 2 weeks. During postprandial day (Day 14), subjects are requested to consume breakfast meal containing 50g of fat and 100mL of milkshake, follow by capsule consumption<br>* Other names: TOCOVID SupraBio 200mg;|
| Experimental: Placebo<br> | Dietary Supplement: Placebo<br>* Placebo is taken twice daily (after breakfast and dinner) for 2 weeks. During postprandial day (Day 14), subjects are requested to consume breakfast meal containing 50g of fat and 100mL of milkshake, follow by capsule consumption<br>* Other names: Palm Olein;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Aggregation | Comparison will be made between Day 14-fasting and changes will be measured between Day 14-fasting and 4hr. | Day 0 - fasting, Day 14 - fasting, Day 14 - 4hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet activation | Comparison will be made between Day 14-fasting and changes will be measured between Day 14-fasting and 4hr. | Day 0 - fasting, Day 14 - fasting, Day 14 - 4hr | 
| Haemostatic markers (Plasminogen activator inhibitor type 1 and sP-selectin) | Comparison will be made between Day 14-fasting and postprandial response will be compared between two interventions | Day 0 - fasting, Day 14 - fasting, Day 14 - 2hr, Day 14 - 4hr, Day 14 - 6 hr | 
| Inflammatory markers (sE-selectin, sICAM-1, and sVCAM-1) | Comparison will be made between Day 14-fasting and postprandial response will be compared between two interventions | Day 0 - fasting, Day 14 - fasting, Day 14 - 4hr | 
| Lipid Profile | Comparison will be made between Day 14-fasting | Day 0 - fasting, Day 14 - fasting | 
| D-dimer | Comparison will be made between Day 14-fasting and postprandial response will be compared between two interventions | Day 0 - fasting, Day 14 - fasting, Day 14 - 4hr | 
| Full blood count and liver function test | Comparison will be made between Day 14-fasting | Day 0-fasting and Day 14-fasting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tocotrienols, Platelet aggregation, Metabolic syndrome, Platelet activation, Thrombosis