Stroke and Tocotrienol: Unique Role in Neuroprotection (SATURN)

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

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.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke
• Intervention / Treatment: Dietary supplement: Tocotrienol; Dietary supplement: Placebo capsules

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: IRENE LOOI; Email: irenelooi@yahoo.com
• Study Contact Backup: Name: WEN YAO MAK; Email: makwenyao@gmail.com

Study Locations

• Malaysia
  • Pulau Pinang
    • Seberang Jaya, Pulau Pinang, Malaysia, 13700
      • Recruiting
      • Seberang Jaya Clinical Research Centre
      • Contact: IRENE LOOI; Email: irenelooi@yahoo.com
      • Contact: AWATIF RUSLI; Email: awatif90rusli@gmail.com
      • Principal Investigator: Irene Looi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Adult patients within 1-10 days ischaemic stroke of moderate severity (NIHSS 6-20)

Inclusion Criteria:

1. Age 35 years old and above.
2. 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.
3. Subject is neurologically stable after stroke onset, i.e. no fluctuation in clinical conditions.
4. Subject has a modified Rankin Scale from 2-4.
5. Subject has a clinical stroke diagnosis according to WHO stroke diagnosis.
6. Subject is willing to attend at least four sessions of physiotherapy during the study or as deemed needed by the physiotherapist
7. Subjects or his/her legally acceptable representative is willing to provide written informed consent.

Exclusion Criteria:

1. Subject has evidence of intra-cerebral hemorrhage on brain CT scan or MRI
2. Recurrent stroke or previous hospitalisation due to suspected cerebrovascular event.
3. Severe stroke as assessed clinically and/or by appropriate imaging techniques
4. Subject has other significant non-ischemic brain lesion(s) which could affect function or disability.
5. Time of ischemic stroke onset not exactly known
6. 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)
7. Subject has active systemic infection such as (but not limited to) hepatitis and pneumonia
8. Subject has definite indication for full dose or long term anti-coagulation therapy (such as warfarin)
9. Any condition that in the judgment of the investigator would place the patient under undue risk
10. Traumatic brain injury within the previous 30 days.
11. Symptoms which are rapidly improving (as in transient ischemic stroke)
12. 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.
13. Patients who have been included in any other clinical trial within the previous three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seberang Jaya Clinical Research Centre
• Collaborators: Universiti Sains Malaysia; Clinical Research Centre Hospital Taiping
• Investigators: Principal Investigator: IRENE LOOI, SEBERANG JAYA HOSPITAL CLINICAL RESEARCH CENTRE; Study Director: KAH HAY YUEN, Universiti Sains Malaysia

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimate): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 9, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: 2013-CRC-001-03