Stroke and Tocotrienol: Unique Role in Neuroprotection

Study Overview
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Brief Summary
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Phase III, single-centre, double-blind, randomised, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of oral Vitamin E (Mixed Tocotrienol) for 6 months in patients with moderate ischemic stroke. 150 patients will be recruited and randomized to receive either placebo or mixed tocotrienol 200mg twice a day for 6 months. Patients will be followed up and assessed on their functional recovery.

Official Title
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Phase III, Single Centre, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial to Evaluate the Efficacy and Safety of Oral Vitamin E (Mixed Tocotrienol) for 6 Months in Patients With Moderate Acute Ischemic Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Dietary Supplement: Tocotrienol
* Dietary Supplement: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Adult patients within 1-10 days ischaemic stroke of moderate severity (NIHSS 6-20) Inclusion Criteria: Age 35 years old and above. Subject will be included within the time frame of 1-10 days after the first onset of acute cerebral ischaemic stroke with NIHSS between 6 - 20. Subject is neurologically stable after stroke onset, i.e. no fluctuation in clinical conditions. Subject has a modified Rankin Scale from 2-4. Subject has a clinical stroke diagnosis according to WHO stroke diagnosis. Subject is willing to attend at least four sessions of physiotherapy during the study or as deemed needed by the physiotherapist Subjects or his/her legally acceptable representative is willing to provide written informed consent. Exclusion Criteria: Subject has evidence of intra-cerebral hemorrhage on brain CT scan or MRI Recurrent stroke or previous hospitalisation due to suspected cerebrovascular event. Severe stroke as assessed clinically and/or by appropriate imaging techniques Subject has other significant non-ischemic brain lesion(s) which could affect function or disability. Time of ischemic stroke onset not exactly known Subject has documented underlying medical conditions which may affect assessment or follow-up such as (but not limited to) terminal cancer, liver cirrhosis, severe dementia or psychosis, connective tissue disease, rheumatoid arthritis, severe heart disease, severe liver disease or renal failure (based on recent medical history) Subject has active systemic infection such as (but not limited to) hepatitis and pneumonia Subject has definite indication for full dose or long term anti-coagulation therapy (such as warfarin) Any condition that in the judgment of the investigator would place the patient under undue risk Traumatic brain injury within the previous 30 days. Symptoms which are rapidly improving (as in transient ischemic stroke) The patient is pregnant, breast feeding or female of childbearing potential (unless the subject is willing to practice on double contraception measures for the study duration) until up to 1 month (30 days) after last treatment dose. Patients who have been included in any other clinical trial within the previous three months.

Ages Eligible for Study
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Minimum Age: 35 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to receive either placebo or investigational drug (mixed tocotrienols dietary supplement) for 6 months.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Tocotrienol<br>Mixed tocotrienol 200mg twice a day for 6 months | Dietary Supplement: Tocotrienol<br>* Subjects in the intervention arm will take one capsule of 200mg tocotrienol twice daily for 6 months<br>|
| Placebo Comparator: Placebo (for tocotrienol)<br>Placebo capsules, 1 capsule twice a day for 6 months | Dietary Supplement: Placebo capsules<br>* Subjects in the placebo arm will take one capsule of placebo twice daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Score | Shift in modified Rankin Score (mRS) at 6 months of treatment (odds ratio) | 6th Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Score | Shift in modified Rankin Score (mRS) at 3 months of treatment (odds ratio) | 3rd month | 
| Modified Barthel Index | • Increment in the score of Modified Barthel Index at the end of 6 months of treatment from baseline (before treatment) | 6th months | 
| NIHSS | Reduction in NIHSS at the end of 6 months of treatment from baseline | before dosing and at 6th month | 
| Composite score (MRS, NIHSS, mBI) | Proportion of patients achieving favourable composite score of mRS 0 - 2, NIHSS <6, and mBI at least 95 | 6th month | 
| Modified Rankin Score | Proportion of patients achieving modified Rankin Score (mRS) of 0 - 2 at 3 months of treatment | 3rd month | 
| Modified Rankin Score | Proportion of patients achieving modified Rankin Score (mRS) of 0 - 2 at 6 months of treatment | 6th month | 
| MRI - Brain lesion volume | Change in stroke lesion volume | 6th month | 
| SF-36 | quality of life | 6th month | 
| CLOX and TMT Parts A & B | Improvement in the score of CLOX and TMT Parts A & B at the end of 24-weeks of treatment from baseline | 6th month | 
| Adverse event monitoring | Adverse event outcomes in both groups | 6 months |