The purpose of this study is to evaluate the safety of administration and effects of valproic acid on clusterin expression in cognitively-intact, healthy, elderly subjects. Clusterin mutations have recently been identified as a risk factor for the development of Alzheimer's Disease and changes in clusterin expression are seen in the elderly who develop Alzheimer's disease irrespective of whether they carry these genetic mutations or not. Valproic acid may prevent or reverse these changes. Fourteen subjects with normal memory and thinking will participate in this study. Ten of these subjects will receive valproic acid and 4 will receive a "placebo" capsule with no active medicine. Participants will take study medication or placebo for 28 days and be followed for a total 35 days in this trial.
This is a placebo-controlled, single-center, multiple ascending dose study. Seven healthy volunteers will be enrolled into 2 sequential cohorts, for a total of 14 enrolled subjects. The study will be conducted using two doses of valproate (250 mg PO bid, followed by 500 mg PO bid). At each dose level, 7 cognitively intact normal elderly subjects will be entered into the study with two subjects randomly selected to receive placebo while the other five subjects receive the designated dose of valproate. Study procedures will include routine assessment of adverse events, safety labs, baseline MRI, physical and neurological exams, and cerebrospinal fluid collection. Other investigational medication or devices are prohibited during this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
14
generic valproic acid tablets packaged in placebo-matched capsules.
Placebo capsule without active study medication in identical capsules as experimental medicine.
Sander's Brown Center on Aging
Lexington, Kentucky, United States
Frequency of Adverse Events Over the Duration of the Study by Study Arm
Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests throughout the study. The incidence of observed toxicities and adverse events will be tabulated, the frequencies compared in participants who receive active medication and those who receive placebo, and reviewed for potential significance and clinical importance.
Time frame: Day 35
Change in Cerebrospinal Fluid Amyloid Levels (pg/ml) Over 28 Day Intervention Period by Study Arm
Change in cerebrospinal fluid amyloid-beta 1-42 levels in pg/ml from baseline to end of treatment (day 28)
Time frame: Baseline and day 28
Change in Cerebrospinal Fluid P-tau Levels (pg/ml)
Change in cerebrospinal fluid p181-tau levels (pg/ml) from baseline to end of treatment (Day 28)
Time frame: Baseline and day 28
Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct)
Change in Free \& Cued Selective Reminding Test- delayed free recall from baseline to end of treatment (Day 28)
Time frame: Baseline and day 28
Change in Cerebrospinal Fluid Clusterin Levels (pg/ml)
Change in cerebrospinal fluid clusterin levels (pg/ml) from baseline to end of treatment (Day 28)
Time frame: Baseline and day 28
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