Neuroprotection by Tocotrienols in Type 1 and Type 2 Diabetes Mellitus (VENUS)
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|ClinicalTrials.gov Identifier: NCT01973400|
Recruitment Status : Completed
First Posted : October 31, 2013
Last Update Posted : May 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Diabetic Neuropathy Cognitive Impairment||Dietary Supplement: Tocotrienol Dietary Supplement: Placebo||Phase 3|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Supportive Care|
|Official Title:||A Clinical Study on the Neuroprotection by Tocotrienols in Type 1 and Type 2 Diabetes Mellitus|
|Study Start Date :||June 2011|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||December 2016|
200 mg, twice a day, 12 months
Dietary Supplement: Tocotrienol
Palm-Oil derived Vitamin E, tocotrienol
Placebo Comparator: Placebo
200 mg, twice a day, 12 months
Dietary Supplement: Placebo
- Total Symptoms Score (TSS) (pain, paresthesia, burning, and numbness)of patients with diabetes type 1 and 2 neuropathy. [ Time Frame: 1 year ]
- Neuropathy Impairment Score (NIS) of patients with diabetes type 1 and 2 neuropathy [ Time Frame: 1 year ]
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01973400
|Seberang Jaya Hospital|
|Seberang Jaya, Penang, Malaysia, 13700|
|Principal Investigator:||Kah Hay Yuen, PhD||Universiti Sains Malaysia|