Cerebrovascular DisordersPhase 2NCT00753532
Neuroprotective and Cardioprotective Effects Of Palm Vitamin E Tocotrienols
A Phase 2 study of Cerebrovascular Disorders, run by Universiti Sains Malaysia at 1 site in Malaysia.
Trial summary
The purpose of the study is to assess the neuroprotective, anti atherogenic and hepatoprotective properties of tocotrienols (palm vitamin E) supplementation as determined by white matter lesion load on serial magnetic resonance imaging (MRI), carotid artery magnetic resonance angiography (MRA) and liver ultrasound… Read more about this study
- Who is it for?
- Ages 35 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cerebrovascular Disorders
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 241 participants
- Where
- 1 siteMalaysia
- Study dates
- Nov 2007to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant able to understand and has signed and dated the Informed Consent Form
- Participant can be either a male or female
- Participant is more than 35 years of age
- Participant has total cholesterol between 5.2 - 6.2 mmol/L and LDL cholesterol between 2.6 - 4.2 mmol/L
- Participant is able to comply with visits and medications
- Participant has normal liver function (total protein, total albumin, total globulin, total bilirubin, SGOT and SGPT)
Show all 12Show fewer
- Participants who satisfy the Inclusion and Exclusion Criteria for Study in General with one or more of the following conditions will be eligible for MRI screening:
- More than 40 years of age
- Stable hypertension requiring only out-patient management
- Diabetes mellitus requiring only out-patient management
- Ischaemic heart disease requiring only out-patient management
- Body mass index more than 25 (overweight or obese)
Who cannot join
- Female participants who are pregnant
- Participant has previously received vitamin E supplementation (tocotrienols or tocopherols) within the past 3 months at the time of recruitment
- Participant has a history of cancer or has undergone radiation therapy
- Participant has a history of major organ dysfunction, such as moderate or severe hepatic impairment, severe renal insufficiency, severe or unstable cardiovascular, respiratory, hematological, endocrinological, neurological or other somatic disorders resulting in previous hospitalization.
- Participant has a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol.
- Participant is requiring long term anti-epileptics, hypnotics, and chronic medications for hypercholesterolemia
Show all 19Show fewer
- Participant has very high cholesterol levels, total cholesterol above 6.2 mmol/L and LDL cholesterol above 4.2 mmol/L, which require medical treatment.
- Participant is requiring long term non-steroidal anti-inflammatory (NSAID) medication.
- Participant has a history of hypersensitivity to vitamin E.
- Participant has signs of alcohol and drug dependence or abuse.
- Participant is unable to understand and comply with the elements in the consent form.
- In addition, the participant must not have any contraindication to have MRI examinations including:
- Biostimulators (e.g. cardiac pacemaker and implanted spinal cord stimulator)
- Neurostimulators
- Aneurysm clips in the brain
- Cochlear implants
- Hearing aids
- Orthopaedic implants less than 2 months old
- Metal fragments in eyes Any further implants or foreign body not listed above should have the safety assessed by a radiologist prior to recruitment into the MRI study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double Blind Placebo Controlled Study On The Neuroprotective And Anti-Atherogenic Effects Of Palm TocotrienolRich Fraction(Palm Vitamin E)
The purpose of the study is to assess the neuroprotective, anti atherogenic and hepatoprotective properties of tocotrienols (palm vitamin E) supplementation as determined by white matter lesion load on serial magnetic resonance imaging (MRI), carotid artery magnetic resonance angiography (MRA) and liver ultrasound (US) as well as lipid profile analysis.
Read the detailed description
Stroke is the third largest cause of death after heart disease and cancer in Malaysia. It is estimated that 52,000 Malaysians suffer stroke annually. In 2005, 3245 cases of stroke were fatal. It is projected that the number of fatal stoke cases will exceed 25,000 in 2020.
It was found that at nanomolar concentrations, α-tocotrienol but not α-tocopherol prevent glutamate-induced neuron cell death in mice through inhibition of c-Src kinase and 12-lipoxygenase. Tocotrienol-supplemented rats showed more protection against stroke-induced injury compared with matched controls.
White matter lesion as detected on magnetic resonance imaging (MRI) is closely related to vascular events of the brain. MRI and histopathological study has shown that the larger white matter lesions not usually conforming to usual areas infarcts can actually represent areas of subclinical infarct. In addition there is positive correlation between white matter lesions with established vascular risk factors.
The Rotterdam Scan Study showed that elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of clinical stroke, which could not be explained by the major stroke risk factors alone.
Several recent studies showed that white matter lesions may be an independent prognostic measure of future stroke risk.
White matter hyperintensities as detected on MRI is closely related to vascular events of the brain and in some instances represent subclinical infarcts.
It is therefore conceivable to study the neuroprotective properties of tocotrienol supplementation in humans by looking at serial changes of white matter disease load.
Tocotrienol supplementation brings about various favourable effects including improving lipid profiles, lowering of thromboxane B2 and platelet factor 4 and reduced LDL oxidation. Carotid artery MR angiography is an established and robust technique in the evaluation of carotid artery stenosis. Therefore, to study the anti-atherogenic effects of tocotrienols supplementation, serial MR angiography of the carotid arteries are done.
Non-alcoholic fatty liver disease (NAFLD) is emerging as a not fully understood, both in aetiology and significance, liver disorder. FLD is reported to be the most common cause of chronic liver disease in the U.S.A. and other western countries with a prevalence rate ranging between 15% to 30% of the adult population. However, limited data are available for Malaysia.
US imaging provides valuable information of the liver condition with a sensitivity of 93-100%. Frequently NAFLD is associated with dyslipidemia, obesity, insulin resistance and type II diabetes and it represents the liver component of the metabolic syndrome (MetS). Patients with NAFLD are reported to have low levels of serum vitamin E. NAFLD patients present a significant increase in cardiovascular (CV) risk, thus linking NAFLD, MetS and accelerated atherosclerosis.
- Conditions
- Cerebrovascular Disorders
- Being tested
- 200mg of Palm vitamin E (tocotrienols) or placebo
- Keywords
- Carotid artery stenoses, Brain ischaemia, stroke, Lipid abnormalities, Fatty Liver
- Medical subject headings
- Cerebrovascular Disorders, Carotid Stenosis, Stroke, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
200mg of Palm vitamin E (tocotrienols) or placeboDietary supplement
Also called Tocovid 200mg
Individuals randomized in the (MRI+ve) and (MRI -ve) cohort respectively. In the MRI(+ve) cohort, 62 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 59 were assigned to placebo, taken orally twice a day for a study period of two years. In the MRI(-ve) cohort, 63 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 57 consumed placebo, taken twice a day for a follow up period of 1 year.
| Study group | Role | What they receive |
|---|---|---|
| MRI(+ve), | Placebo comparator | 121 volunteers in MRI(+ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 62 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 59 received placebo. They were followed up every 3 months for a period of 2 years for their blood biochemistry profile and MRI of the brain was conducted at baseline, 12 months and 24 months.. Receives: Dietary Supplement: 200mg of Palm vitamin E (tocotrienols) or placebo |
| MRI(-ve) | Placebo comparator | 120 volunteers in MRI(-ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 63 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 57 received placebo. They were followed up every 3 months for a period of 1 year for their blood biochemistry profile and MRI of the brain was conducted at baseline and 12 months. Receives: Dietary Supplement: 200mg of Palm vitamin E (tocotrienols) or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regression of white matter lesion load in terms of numbers and size in the brain
Measured: 1 to 2 years
Secondary outcomes (3)
Regression of the carotid artery stenoses in terms of percentage
Measured: 1 to 2 years
The improvement in the lipid profile other markers associated with increased cardiovascular risk
Measured: 1 to 2 years
Improvement in liver echogenicity.
Measured: 1 to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2008 (estimated)
- Study startNov 2007
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Sains Malaysia
- Sponsor type
- University, hospital or other
- Collaborators
- Malaysia Palm Oil Board
- Responsible party
- Principal investigator, Yuen Kah Hay, Universiti Sains Malaysia
- Investigators
- Yuen Kah Hay, Phd, Principal investigator, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753532
- Sponsor's protocol ID
- MPOB-USM-Version 1.4
- Status last verified
- May 2022
- First submitted
- 15 Sep 2008
- Last updated
- 25 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014 May;45(5):1422-8. doi: 10.1161/STROKEAHA.113.004449. Epub 2014 Apr 3.
PubMed 24699052Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, Abu Bakar MR, Ng BH, Yuen KH. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr J. 2013 Dec 27;12(1):166. doi: 10.1186/1475-2891-12-166.
PubMed 24373555
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Placebo Controlled Study On The Neuroprotective And Anti-Atherogenic Effects Of Palm TocotrienolRich Fraction(Palm Vitamin E)
- ClinicalTrials.gov ID
- NCT00753532
- Acronym / sponsor ID
- MPOB-USM-Version 1.4
- Conditions
- Cerebrovascular Disorders
- Keywords
- Carotid artery stenoses, Brain ischaemia, stroke, Lipid abnormalities, Fatty Liver
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Universiti Sains MalaysiaUniversity, hospital or other
- Collaborators
- Malaysia Palm Oil Board
- Study start
- Nov 2007
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the neuroprotective, anti atherogenic and hepatoprotective properties of tocotrienols (palm vitamin E) supplementation as determined by white matter lesion load on serial magnetic resonance imaging (MRI), carotid artery magnetic resonance angiography (MRA) and liver ultrasound (US) as well as lipid profile analysis.
Detailed description
Stroke is the third largest cause of death after heart disease and cancer in Malaysia. It is estimated that 52,000 Malaysians suffer stroke annually. In 2005, 3245 cases of stroke were fatal. It is projected that the number of fatal stoke cases will exceed 25,000 in 2020.
It was found that at nanomolar concentrations, α-tocotrienol but not α-tocopherol prevent glutamate-induced neuron cell death in mice through inhibition of c-Src kinase and 12-lipoxygenase. Tocotrienol-supplemented rats showed more protection against stroke-induced injury compared with matched controls.
White matter lesion as detected on magnetic resonance imaging (MRI) is closely related to vascular events of the brain. MRI and histopathological study has shown that the larger white matter lesions not usually conforming to usual areas infarcts can actually represent areas of subclinical infarct. In addition there is positive correlation between white matter lesions with established vascular risk factors.
The Rotterdam Scan Study showed that elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of clinical stroke, which could not be explained by the major stroke risk factors alone.
Several recent studies showed that white matter lesions may be an independent prognostic measure of future stroke risk.
White matter hyperintensities as detected on MRI is closely related to vascular events of the brain and in some instances represent subclinical infarcts.
It is therefore conceivable to study the neuroprotective properties of tocotrienol supplementation in humans by looking at serial changes of white matter disease load.
Tocotrienol supplementation brings about various favourable effects including improving lipid profiles, lowering of thromboxane B2 and platelet factor 4 and reduced LDL oxidation. Carotid artery MR angiography is an established and robust technique in the evaluation of carotid artery stenosis. Therefore, to study the anti-atherogenic effects of tocotrienols supplementation, serial MR angiography of the carotid arteries are done.
Non-alcoholic fatty liver disease (NAFLD) is emerging as a not fully understood, both in aetiology and significance, liver disorder. FLD is reported to be the most common cause of chronic liver disease in the U.S.A. and other western countries with a prevalence rate ranging between 15% to 30% of the adult population. However, limited data are available for Malaysia.
US imaging provides valuable information of the liver condition with a sensitivity of 93-100%. Frequently NAFLD is associated with dyslipidemia, obesity, insulin resistance and type II diabetes and it represents the liver component of the metabolic syndrome (MetS). Patients with NAFLD are reported to have low levels of serum vitamin E. NAFLD patients present a significant increase in cardiovascular (CV) risk, thus linking NAFLD, MetS and accelerated atherosclerosis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MRI(+ve), | Placebo comparator | Dietary Supplement: 200mg of Palm vitamin E (tocotrienols) or placebo121 volunteers in MRI(+ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 62 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 59 received placebo. They were followed up every 3 months for a period of 2 years for their blood biochemistry profile and MRI of the brain was conducted at baseline, 12 months and 24 months.. |
| MRI(-ve) | Placebo comparator | Dietary Supplement: 200mg of Palm vitamin E (tocotrienols) or placebo120 volunteers in MRI(-ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 63 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 57 received placebo. They were followed up every 3 months for a period of 1 year for their blood biochemistry profile and MRI of the brain was conducted at baseline and 12 months. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Participant able to understand and has signed and dated the Informed Consent Form
- Participant can be either a male or female
- Participant is more than 35 years of age
- Participant has total cholesterol between 5.2 - 6.2 mmol/L and LDL cholesterol between 2.6 - 4.2 mmol/L
- Participant is able to comply with visits and medications
Key exclusion criteria (19 listed)
- Female participants who are pregnant
- Participant has previously received vitamin E supplementation (tocotrienols or tocopherols) within the past 3 months at the time of recruitment
- Participant has a history of cancer or has undergone radiation therapy
- Participant has a history of major organ dysfunction, such as moderate or severe hepatic impairment, severe renal insufficiency, severe or unstable cardiovascular, respiratory, hematological, endocrinological, neurological or other somatic disorders resulting in previous hospitalization.
- Participant has a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 200mg of Palm vitamin E (tocotrienols) or placeboAlso: Tocovid 200mgIndividuals randomized in the (MRI+ve) and (MRI -ve) cohort respectively. In the MRI(+ve) cohort, 62 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 59 were assigned to placebo, taken orally twice a day for a study period of two years. In the MRI(-ve) cohort, 63 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 57 consumed placebo, taken twice a day for a follow up period of 1 year. | Dietary supplement | MRI(+ve),, MRI(-ve) |
Primary outcome
Regression of white matter lesion load in terms of numbers and size in the brain
Time frame: 1 to 2 years
3 secondary outcomes
Regression of the carotid artery stenoses in terms of percentage
Time frame: 1 to 2 years
The improvement in the lipid profile other markers associated with increased cardiovascular risk
Time frame: 1 to 2 years
Improvement in liver echogenicity.
Time frame: 1 to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2022.
- Derived from this study: PubMed 24699052Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, Khan NA, Liong WC, Sundram K, Ng BH, Karuthan C, Yuen KH. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014 May;45(5):1422-8. doi: 10.1161/STROKEAHA.113.004449. Epub 2014 Apr 3.
- Derived from this study: PubMed 24373555Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, Abu Bakar MR, Ng BH, Yuen KH. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr J. 2013 Dec 27;12(1):166. doi: 10.1186/1475-2891-12-166.
Related trials for Cerebrovascular Disorders
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuen Kah Hay, Phd principal investigator
Universiti Sains Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Cerebrovascular Disorders, run by Universiti Sains Malaysia at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regression of white matter lesion load in terms of numbers and size in the brain (time frame: 1 to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00753532, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2022.