Valproic Acid in Subjects With Intact Cognition - Proof of Concept Study (VPA)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
|Official Title:||Safety And Target Engagement Of Clu1 By Valproic Acid In Subjects With Intact Cognition: Proof Of Concept For The Development Of A Prevention Trial For Alzheimer's Disease|
- Frequency of adverse events [ Time Frame: Day 35 ] [ Designated as safety issue: Yes ]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.
- Change in cerebrospinal fluid amyloid levels [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
- Change in cerebrospinal fluid tau levels [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
- Cognitive tests [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
- Change in cerebrospinal fluid clusterin levels [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Valproic Acid
Valproic acid 250 mg or 500mg by mouth twice daily.
Drug: Valproic Acid
generic valproic acid tablets packaged in placebo-matched capsules.
Placebo Comparator: Placebo
Placebo capsule by mouth twice daily.
Placebo capsule without active study medication in identical capsules as experimental medicine.
Other Name: Sugar pill
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01729598
|United States, Kentucky|
|Sander's Brown Center on Aging|
|Lexington, Kentucky, United States, 40536|
|Principal Investigator:||Steve Estus, PhD||University of Kentucky|
|Principal Investigator:||Gregory Jicha, MD||University of Kentucky|