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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Platelet Aggregation, Spontaneous
• Intervention / Treatment: Dietary supplement: Tocotrienol-rich fraction 400mg; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
      • Malaysia Palm Oil Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Dietary supplement: Placebo; 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; Other Names: Palm Olein
Experimental: Tocotrienol-rich fraction 400mg	Dietary supplement: Tocotrienol-rich fraction 400mg; 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; Other Names: TOCOVID SupraBio 200mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Malaysia Palm Oil Board
• Collaborators: Universiti Putra Malaysia
• Investigators: Principal Investigator: Ju Yen Fu, PhD, Malaysia Palm Oil Board

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 28, 2012
• First Posted (Estimate): June 29, 2012

Study Record Updates

• Last Update Posted (Estimate): December 20, 2013
• Last Update Submitted That Met QC Criteria: December 19, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Thrombosis; Platelet aggregation; Platelet activation; Tocotrienols
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols; Tocovid
• Other Study ID Numbers: PD157/11