Ignite Creation Date:
2024-05-05 @ 12:04 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00235716
Status:
COMPLETED
Last Update Posted:
2014-07-23
First Post:
2005-10-06
Brief Title:
A Randomized Clinical Trial of Vitamin E and Memantine in Alzheimers Disease
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 546 - A Randomized Clinical Trial of Vitamin E and Memantine in Alzheimers Disease TEAM-AD
Status:
COMPLETED
Status Verified Date:
2014-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TEAM-AD
Brief Summary:
The purpose of this study is to determine whether alpha-tocopherol memantine Namenda or the combination will significantly delay clinical progression in mild to moderately demented patients with Alzheimers disease compared to placebo
Detailed Description:
Abstract Alzheimers disease AD a neurodegenerative disorder resulting in cognitive loss behavioral problems and functional decline is characterized by well-established and well-known neuropathological changes in the brain Cognitive deficits and behavioral symptoms are thought to be due to cholinergic neuronal degeneration and loss associated with oxidative stress and inflammatory responses
Current therapeutic strategies include efforts to
1 enhance cholinergic neuronal function
2 promote neuroprotective effects and
3 block pathologic activity of excessive glutamate with a moderate-affinity NMDA antagonist
A combination of pharmacological therapies directed at simultaneously improving neuronal function and neuroprotection would presumably be more effective than either treatment alone
To test this hypothesis this study will examine the efficacy of drug treatment with a combination of
1 any of three FDA approved cholinesterase inhibitors that facilitates central acetylcholine neurotransmission donepezil rivastigmine galantamine
2 alpha-tocopherol a fat soluble vitamin that has been shown to slow the rate of progression of AD presumably through neuroprotective mechanism that reduces oxidative stress and
3 memantine a moderate-affinity NMDA antagonist that blocks excessive stimulation of NMDA receptors by glutamate CSP546 will be a double-blind placebo-controlled randomized clinical trial to assess the efficacy of adding alpha-tocopherol memantine and the combination for the treatment of functional decline in mild-to-moderately demented patients with Alzheimers disease MMSE 12-26 who are currently taking an acetylcholinesterase inhibitor AchEI
Eligible Veterans will be randomly assigned to either
1 2000 IUd of alpha-tocopherol plus memantine placebo
2 20 mgd of memantine Namenda plus alpha-tocopherol placebo
3 2000 IUd of alpha-tocopherol plus 20 mgd of memantine or
4 alpha-tocopherol placebo plus memantine placebo
The primary outcome for the study will be progression of AD as measured by the Alzheimers Disease Cooperative StudyActivities of Daily Living ADCSADL inventory The ADCSADL inventory is an established outcome measure that was designed to assess functional capacity over a broad range of dementia severity and to be sensitive in measuring dementia progression Secondary outcome measures will include the following five instruments Alzheimers Disease Assessment Scale - Cognitive Subscale ADAS-cog cognition MMSE cognition The Dependence Scale function Neuropsychiatric Inventory NPI behavior and Caregiver Activity Survey CAS caregiver time Outcomes and safety assessments will be obtained at baseline and every six months The target sample size for the trial will be 620 patients 210 per treatment arm This sample size will provide 90 power to detect a 4-point mean treatment difference in the ADCSADL inventory by the end of the average follow-up period adjusted for losses The effects to be detected are modest and translate into a 177 reduction in the annual rate of decline with each therapy given alone and if the effects are additive an approximate 35 reduction for combined therapy These effects are equivalent to slowing the rate of progression of the disease by nearly 6 months for monotherapy and 12 months for combined therapy To achieve the target sample size Veterans will be recruited over a 3-year period with an estimated minimum follow-up of 1 year and a maximum of 4 years A total of 10 to 15 VA sites will be established to enroll an average of one Veteran every 2 weeks CSP546 is designed to assess both a clinically and economically important treatment effect If the study definitely determined that alpha-tocopherol memantine or the combination delays the progression of AD the study would be tremendously valuable in reducing the financial and emotional costs of the disease in the VA and US as a whole
Current therapeutic strategies include efforts to
1 enhance cholinergic neuronal function
2 promote neuroprotective effects and
3 block pathologic activity of excessive glutamate with a moderate-affinity NMDA antagonist
A combination of pharmacological therapies directed at simultaneously improving neuronal function and neuroprotection would presumably be more effective than either treatment alone
To test this hypothesis this study will examine the efficacy of drug treatment with a combination of
1 any of three FDA approved cholinesterase inhibitors that facilitates central acetylcholine neurotransmission donepezil rivastigmine galantamine
2 alpha-tocopherol a fat soluble vitamin that has been shown to slow the rate of progression of AD presumably through neuroprotective mechanism that reduces oxidative stress and
3 memantine a moderate-affinity NMDA antagonist that blocks excessive stimulation of NMDA receptors by glutamate CSP546 will be a double-blind placebo-controlled randomized clinical trial to assess the efficacy of adding alpha-tocopherol memantine and the combination for the treatment of functional decline in mild-to-moderately demented patients with Alzheimers disease MMSE 12-26 who are currently taking an acetylcholinesterase inhibitor AchEI
Eligible Veterans will be randomly assigned to either
1 2000 IUd of alpha-tocopherol plus memantine placebo
2 20 mgd of memantine Namenda plus alpha-tocopherol placebo
3 2000 IUd of alpha-tocopherol plus 20 mgd of memantine or
4 alpha-tocopherol placebo plus memantine placebo
The primary outcome for the study will be progression of AD as measured by the Alzheimers Disease Cooperative StudyActivities of Daily Living ADCSADL inventory The ADCSADL inventory is an established outcome measure that was designed to assess functional capacity over a broad range of dementia severity and to be sensitive in measuring dementia progression Secondary outcome measures will include the following five instruments Alzheimers Disease Assessment Scale - Cognitive Subscale ADAS-cog cognition MMSE cognition The Dependence Scale function Neuropsychiatric Inventory NPI behavior and Caregiver Activity Survey CAS caregiver time Outcomes and safety assessments will be obtained at baseline and every six months The target sample size for the trial will be 620 patients 210 per treatment arm This sample size will provide 90 power to detect a 4-point mean treatment difference in the ADCSADL inventory by the end of the average follow-up period adjusted for losses The effects to be detected are modest and translate into a 177 reduction in the annual rate of decline with each therapy given alone and if the effects are additive an approximate 35 reduction for combined therapy These effects are equivalent to slowing the rate of progression of the disease by nearly 6 months for monotherapy and 12 months for combined therapy To achieve the target sample size Veterans will be recruited over a 3-year period with an estimated minimum follow-up of 1 year and a maximum of 4 years A total of 10 to 15 VA sites will be established to enroll an average of one Veteran every 2 weeks CSP546 is designed to assess both a clinically and economically important treatment effect If the study definitely determined that alpha-tocopherol memantine or the combination delays the progression of AD the study would be tremendously valuable in reducing the financial and emotional costs of the disease in the VA and US as a whole
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None