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Sponsors and Collaborators: |
National Institute on Aging (NIA) Alzheimer's Disease Cooperative Study (ADCS) |
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Information provided by: | National Institute on Aging (NIA) |
ClinicalTrials.gov Identifier: | NCT00071721 |
The purpose of this trial is to demonstrate whether valproate therapy delays the emergence of agitation and/or psychosis in outpatients with probable Alzheimer's disease (AD) who have not experienced agitation and psychosis in their illness. A secondary aim is to determine whether valproate therapy delays the progression of cognitive and functional measures of the illness. This trial will also assess the tolerability and safety of low-dose, long-term valproate therapy. Valproate, an anticonvulsant drug, was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD.
Condition | Intervention | Phase |
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Alzheimer Disease |
Drug: Valproate Drug: Placebo |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Randomized, Double-Blind, Placebo-Controlled Trial of Valproate to Attenuate the Progression of Alzheimer's Disease (AD) |
Estimated Enrollment: | 300 |
Study Start Date: | October 2003 |
Estimated Study Completion Date: | October 2008 |
Estimated Primary Completion Date: | October 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental |
Drug: Valproate
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
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2: Placebo Comparator |
Drug: Placebo
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
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This study represents a novel clinical trial strategy designed to assess both prospective "prophylactic" therapy for psychopathology in Alzheimer's disease (AD) and to assess an approach that may alter several aspects of the pathophysiology of AD, and perhaps result in alteration of clinical progression of illness. Interpretation of these results will be supported by study of relevant biomarkers and imaging data. Valproate was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to participants with AD who lack agitation and psychosis at baseline will delay the emergence of agitation and/or psychosis. An effect of this nature may have significant public health implications, for instance, by delaying institutionalization.
This is a randomized, placebo-controlled, double blind, multicenter 26-month trial of valproate therapy at a target dose of 10-12 mg/kg/day in 300 outpatients with mild to moderate Alzheimer's Disease (AD) who lack agitation and psychosis at baseline and since onset of illness. Participants will have regular clinic visits as well as telephone contacts for assessment of behavior, cognition, function, safety and tolerability. The chief secondary aim is to determine whether valproate administration to participants with AD will attenuate clinical progression of illness measured by a reduced rate of cognitive or functional decline. In addition, issues related to safety and tolerability with low-dose (10-12 mg/kg/day) therapy will be addressed. Biological specimens will be obtained to study markers selected for their relevance to the disease as well as the postulated mechanism of action of the valproate therapy. MRI scans will be performed prior to experimental treatment and after one year in a subset of participants in order to address possible drug-placebo differences in brain volume measures.
Approximately 300 participants from 25-35 clinical trial centers in the United States will be enrolled. Participation will include men and women with a diagnosis of probable Alzheimer's disease, age 55 or older, weighing at least 40 kg (88.2 lbs.), residing in the community at baseline, MMSE 10-20 inclusive, who have not experienced agitation or psychosis since the onset of their illness and who do not require treatment with psychotropic medications with the exception of antidepressants used only for treatment of depressive symptoms and limited use of sedatives for sleep. Participants, their relatives, guardians or authorized representatives and informants will be given ample opportunity to inquire about details of the study. Informed consent forms covering consent for the trial itself as well as the genetic research and biological sample storage and MRI scans will be provided to protect the patient's rights and confidentiality.
Ages Eligible for Study: | 55 Years to 90 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Exceptions to these criteria may be considered on a case-by-case basis at the discretion of the Project Director:
Excluded Medications:
Study Director: | Pierre Tariot, MD | University of Rochester Medical Center, Departments of Psychiatry, Medicine, and Neurology, and the Center for Aging and Developmental Biology |
Responsible Party: | Alzheimer's Disease Cooperative Study ( Paul Aisen, MD ) |
Study ID Numbers: | IA0043, IND 67,222, ADCS Protocol ADC-022-VN |
Study First Received: | October 29, 2003 |
Last Updated: | June 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00071721 |
Health Authority: | United States: Food and Drug Administration |
Alzheimer disease Agitation Psychosis |
Alzheimer Disease Disease Progression Central Nervous System Diseases Psychomotor Agitation Brain Diseases Neurodegenerative Diseases Valproic Acid |
Cognition Disorders Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Psychotic Disorders Dementia Delirium |
Neurotransmitter Agents Tranquilizing Agents Molecular Mechanisms of Pharmacological Action Nervous System Diseases Physiological Effects of Drugs Psychotropic Drugs Central Nervous System Depressants Enzyme Inhibitors |
Antimanic Agents Pharmacologic Actions Therapeutic Uses GABA Agents Tauopathies Central Nervous System Agents Anticonvulsants |