NUTRITION: Natural Tocotrienol Against Ischemic Stroke Event (NUTRITION)

Human Blood Outcomes Following Tocotrienol Supplementation - NUTRITION Phase I and Phase IIA

A natural form of vitamin E called tocotrienol (TCT), found in many common foods such as barley, decreases stroke size in animal models. Vitamin E has blood-thinning properties and lowers cholesterol, which make it a potential therapy for stroke prevention, though these effects are less well characterized for TCT. We plan to conduct two trials (I & IIA) to determine the effects of orally supplemented TCT on platelet function and cholesterol.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Transient Ischemic Attack (TIA)
• Intervention / Treatment: Other: Vitamin E tocotrienol (TCT) capsules ; Low dose Aspirin; Other: Placebo vehicle control

Detailed Description

A natural form of vitamin E called tocotrienol (TCT), found in many common foods such as barley, decreases stroke size in animal models. Vitamin E has blood-thinning properties and lowers cholesterol, which make it a potential therapy for stroke prevention, though these effects are less well characterized for TCT. We plan to conduct two trials (I & IIA) to determine the effects of orally supplemented TCT on platelet function and cholesterol. Phase I subjects will be healthy volunteers, recruited by an advertisement. Phase IIA subjects will be hyperlipidemic (having high cholesterol), and will be referred to us by their Wound Care Center Physicians. Patients will be randomized to receive placebo pills, (400 or 800 mg) TCT pills, low-dose 81 mg aspirin (commonly used for secondary prevention of stroke), or TCT and aspirin together. Potential subjects for Phase-I who meet study criteria and agree to participate will be in the study for 6 months and have the following study related procedures, blood draw total 4 times, tape stripping (non-invasive procedure), BMI, and blood pressure measurement at each visit (every month). Participants in Phase-IIA will have blood drawn a total of 6 times, tape stripping, BMI and blood pressure measurement and participants will be in the study for 13 months.

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Phase IA

Inclusion Criteria:

• Healthy subjects between 40 and 70 years of age
• No history of long-term vitamin E supplement (defined as daily oral tocopherol or tocotrienol supplementation greater than or equal to 6mos; within the past 5 years)
• No current vitamin E supplementation in multivitamin

Exclusion Criteria - (as self reported by potential participants during review of eligibility criteria with Research Nurse,)

• Evidence of heart disease as diagnosed by a physician by one or more of the following tests; EKG, chest x-ray, stress test, tilt table test, echocardiogram, coronary angiogram, electrophysiology test, CT heart scan, coronary MRI, pericardiocentesis
• High cholesterol (total cholesterol >240mg/dL, LDL>160mg/dL)
• Prior cancer diagnosis
• Pregnancy - To exclude the possibility of pregnant women entering the study or becoming pregnant during the study only post-menopausal women or women who have had hysterectomies or bilateral oophorectomies will be included.
• Breast feeding
• Smoker (Must have quit 5 or more years ago)
• Alcohol dependence (>4 drinks per day for more than 1yr anytime in the last 3 years)
• Medication exclusion criteria - current use or recent discontinuation (within last 28 days) of any medication including the following: anti-coagulants and blood-thinners (e.g., Warfarin), psychotropic medications including antipsychotics, mood-stabilizers (e.g., lithium, valproic acid, carbamazepine/tegretol); anti-depressants (tricyclics, SSRI's, MAOI's, nonselective MAOIs, Wellbutrin, St. John's Wort); anti-anxiety/anti-panic agents; anti-obsessive agents; prescription stimulants (e.g., Provigil, Ritalin); diet pills/anorectics; daily medication for chronic pain (e.g., opiates) or muscle spasms; daily use of over the counter stimulants in pill form (e.g., ephedrine); daily medication for asthma, Parkinson's disease medications (e.g., levodopa, methyldopa, apomorphine), smoking cessation medications (Wellbutrin/Zyban, Chantix/varenicline); statin use is not grounds for exclusion.

Phase IIA

Inclusion Criteria:

• Hyperlipidemic patients between 40 and 70 years of age currently taking statins
• LDL>130mg/dL
• TG>150mg/dL
• HDL<40mg/dL
• No history of long-term vitamin E supplement (defined as daily oral tocopherol or tocotrienol supplementation greater than or equal to 6mos; within the past 5 years)
• No current vitamin E supplementation in multivitamin

Exclusion Criteria:

• Evidence of heart disease as diagnosed by a physician by one or more of the following tests; EKG, chest x-ray, stress test, tilt table test, echocardiogram, coronary angiogram, electrophysiology test, CT heart scan, coronary MRI, pericardiocentesis
• Prior cancer diagnosis
• Currently taking blood thinners
• Pregnancy - To exclude the possibility of pregnant women entering the study or becoming pregnant during the study only post-menopausal women or women who have had hysterectomies or bilateral oophorectomy will be included.
• Breast feeding
• Smoking (Must have quit within the past 6 months)
• Alcohol dependence - (>4 drinks per day for more than 1yr anytime in the last 3 years)
• Medication exclusion criteria - current use or recent discontinuation (within last 28 days) of any medication including the following: anti-coagulants and blood-thinners (e.g., Warfarin), psychotropic medications including antipsychotics, mood-stabilizers (e.g., lithium, valproic acid, carbamazepine/tegretol); anti-depressants (tricyclics, SSRI's, MAOI's, nonselective MAOIs, Wellbutrin, St. John's Wort); anti-anxiety/anti-panic agents; anti-obsessive agents; prescription stimulants (e.g., Provigil, Ritalin); diet pills/anorectics; daily medication for chronic pain (e.g., opiates) or muscle spasms; daily use of over the counter stimulants in pill form (e.g., ephedrine); daily medication for asthma, Parkinson's disease medications (e.g., levodopa, methyldopa, apomorphine), smoking cessation medications (Wellbutrin/Zyban, Chantix/varenicline)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Volunteers; Healthy participants randomized into one of 6 groups that will take 4 capsules, twice a day of vitamin E tocotrienol (TCT) capsules ; Low Dose Aspirin or placebo capsule for 7 months.	Other: Vitamin E tocotrienol (TCT) capsules ; Low dose Aspirin; Vitamin E TCT capsules- 400-800 mg Aspirin- 81 mg; Other: Placebo vehicle control; vehicle control compared to Vitamin E TCT pills; Other Names: placebo capsule
Active Comparator: Hyperlipidemic; hyperlipidemic patients randomized into one of 6 groups that will take 4 capsules, twice a day of Vitamin E Tocotrienol (TCT) capsules; Low Dose Aspirin or placebo vehicle control capsule for 7 months.	Other: Vitamin E tocotrienol (TCT) capsules ; Low dose Aspirin; Vitamin E TCT capsules- 400-800 mg Aspirin- 81 mg; Other: Placebo vehicle control; vehicle control compared to Vitamin E TCT pills; Other Names: placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet function panel	Blood draw followed by platelet aggregometry	up to one year
Lipid profile	blood lipid panel including HDL, LDL, total cholesterol	up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tape Stripping Test	HPLC vitamin E analysis of tape strips for compliance	up to one year

Collaborators and Investigators

• Sponsor: Andrew Slivka
• Collaborators: Government of Malaysia

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 5, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (Estimate): April 17, 2012

Study Record Updates

• Last Update Posted (Actual): September 20, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: stroke; ischemia; TIA
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protective Agents; Micronutrients; Vitamins; Antioxidants; Aspirin; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: 2011H0242