Valproic Acid in Subjects With Intact Cognition - Proof of Concept Study (VPA)
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|ClinicalTrials.gov Identifier: NCT01729598|
Recruitment Status : Completed
First Posted : November 20, 2012
Results First Posted : October 9, 2019
Last Update Posted : October 9, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease||Drug: Valproic Acid Drug: Placebo||Early Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, 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|
|Study Start Date :||April 2012|
|Actual Primary Completion Date :||October 2014|
|Actual Study Completion Date :||October 2014|
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
- Frequency of Adverse Events Over the Duration of the Study by Study Arm [ Time Frame: Day 35 ]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 (pg/ml) Over 28 Day Intervention Period by Study Arm [ Time Frame: Baseline and day 28 ]Change in cerebrospinal fluid amyloid-beta 1-42 levels in pg/ml from baseline to end of treatment (day 28)
- Change in Cerebrospinal Fluid P-tau Levels (pg/ml) [ Time Frame: Baseline and day 28 ]Change in cerebrospinal fluid p181-tau levels (pg/ml) from baseline to end of treatment (Day 28)
- Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct) [ Time Frame: Baseline and day 28 ]Change in Free & Cued Selective Reminding Test- delayed free recall from baseline to end of treatment (Day 28)
- Change in Cerebrospinal Fluid Clusterin Levels (pg/ml) [ Time Frame: Baseline and day 28 ]Change in cerebrospinal fluid clusterin levels (pg/ml) from baseline to end of treatment (Day 28)
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): 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|