- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01973400
Neuroprotection by Tocotrienols in Type 1 and Type 2 Diabetes Mellitus (VENUS)
A Clinical Study on the Neuroprotection by Tocotrienols in Type 1 and Type 2 Diabetes Mellitus
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Neuropathy affects approximately 30-50% of all diabetic patients and is the commonest form of neuropathy in the developed world. Pain is the most distressing symptom of neuropathy and the main factor that prompts the patient to seek medical advice. About 16-26% of diabetes patients experience chronic neuropathic pain. An animal study revealed that treating rats with α-tocopherol and tocotrienol for 10 weeks significantly improved all the biochemical and behavioral outcomes of alcohol-induced neuropathy in a dose-dependent manner with more potent effects observed with tocotrienols. The study demonstrates the effectiveness of tocotrienols in attenuation of alcoholic neuropathy.
Cognitive dysfunction is a less addressed and not as well recognized complication of diabetes. Patients with type 1 and type 2 diabetes mellitus have been found to have cognitive deficits that can be attributed to their disease. Both old age and diabetes are independently associated with an increased risk of cognitive dysfunction; the risk is even greater for older adults with diabetes. Cognitive Function is the term used to describe a person's state of consciousness (alertness and orientation), memory, and attention span. It has been suggested that Vitamin E, including tocopherols and tocotrienols, can help to improve cognitive function and stall cognitive decline through its antioxidant effects. A reason for this nutrient's success at preventing oxidative damage in brain cells is its fat-soluble criteria. During the World Alzheimer's Congress held in July 2001, it was reported that high intakes of vitamin E effectively lessened memory loss and cognitive dysfunction among more than 6,000 elderly subjects who were generally taking Vitamin E between 200 to 400 IU per day.
Tocotrienols, in particular α-tocotrienol have been shown to possess neuroprotective effect independent of anti-oxidant activity. Using cell-based studies, α-tocotrienol but not α-tocopherol was shown to prevent glutamate-induced neuronal cell death at nanomolar concentrations. Later studies showed that α-tocotrienol conferred protection against glutamate and stroke-induced neurodegeneration in rats.
In view of the above neuroprotective property of tocotrienols, researchers have proceeded to demonstrate that tocotrienols supplementation helped to reverse neuropathic pain in diabetic rats. It has been postulated the beneficial properties of tocotrienols are due to their suppressive effects on the oxidative-nitrosative stress, inflammatory cytokine release and caspase-3 which are implicated in the pathogenesis of diabetic neuropathy.
In the same year, tocotrienols were shown to prevent cognitive deficits and attenuate alcoholic peripheral neuropathy associated with selective neuronal damage due to chronic alcohol consumption. Moreover, the beneficial effects were found to be more pronounced with tocotrienols compared to tocopherols. It has been postulated that the anti-oxidants property of tocotrienols, the suppression of nitrosative stress and elevated cytokines levels together with acetylcholinesterase activity in the brain regions contributes significantly in preventing the chronic alcohol-induced cognitive deficits in rats.
Yuen and his group are currently conducting a clinical study in human subjects on neuroprotective effects of tocotrienols (NCT00753532). In the study, subjects were followed up for 2 years to determine the volume of white matter lesions on repeated MRI after treatment with tocotrienol as compared to placebo. White matter lesions are related to vascular events in the brain and represent subclinical infarcts, resulting in death/ degeneration of neurons and are positively correlated to cognitive impairment. Preliminary results from an interim analysis are encouraging; patients on tocotrienols shown significant reduction in volume of white matter lesion (confidential communication).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Penang
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Seberang Jaya, Penang, Malaysia, 13700
- Seberang Jaya Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diabetic adults ( both type 1 or 2) ≥20 years old with diabetic peripheral neuropathy with Total Symptom Score(TSS) ≥ 3 points.
- Patients with type 1 diabetes (duration of ≥5 years).
- Patients with type 2 diabetes (at diagnosis).
- Patients with Neuropathy Impairment Score(NIS) > 2
Exclusion Criteria:
- Patients HbA1c >12%.
- Patients with hypoglycemia or conscious impairment at the time of test conduction.
- Patients exhibiting symptoms of peripheral vascular disease with absence of 2 foot pulses on the same foot (Posterior tibialis, Dorsalis pedis)
- Immuno-compromised patients.
- Patients with severe visual impairment, history of psychosis; schizophrenia; bipolar disorder; current depression or brain trauma and patients with alcohol dependence or drug abuse such as cocaine, heroin, etc.
- Those having lesions with a propensity to bleed (e.g., bleeding peptic ulcers), those having a history of hemorrhagic stroke and those with inherited bleeding disorders (e.g., hemophilia) or patients on warfarin.
- Pregnancy and lactation.
- Patients with renal function test of more than 150 umol/L (serum creatinine).
- Patients with liver function test of more than 5 times of the upper normal range
- Active infection or infectious diseases.
- Other significant uncontrolled medical illnesses that may interfere with drug administration or interpretation of results.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: SUPPORTIVE_CARE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Tocotrienol
200 mg, twice a day, 12 months
|
Palm-Oil derived Vitamin E, tocotrienol
|
PLACEBO_COMPARATOR: Placebo
200 mg, twice a day, 12 months
|
Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Total Symptoms Score (TSS) (pain, paresthesia, burning, and numbness)of patients with diabetes type 1 and 2 neuropathy.
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Neuropathy Impairment Score (NIS) of patients with diabetes type 1 and 2 neuropathy
Time Frame: 1 year
|
1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mini Mental State Examination (MMSE) score, Montreal Cognitive Assessment (MoCA) test.
Time Frame: 1 year
|
Measures the effects of tocotrienols on cognitive impairment in type 1 and type 2 diabetes mellitus
|
1 year
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Nervous System Diseases
- Endocrine System Diseases
- Diabetes Complications
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Diabetic Neuropathies
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin E
- Tocopherols
- Tocotrienols
Other Study ID Numbers
- VENUS-7327
- NMRR-10-948-7327 (REGISTRY: National Medical Research Register (Malaysia))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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