Early Phase 1 Completed N=14 Randomized Triple-blind Basic Science

Valproic Acid in Subjects With Intact Cognition - Proof of Concept Study

Alzheimer's Disease

Source: ClinicalTrials.gov NCT01729598 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Oct 2019

Primary outcomePrimary: Frequency of Adverse Events Over the Duration of the Study by Study Arm — 8; 1 Participants

Summary

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Frequency of Adverse Events Over the Duration of the Study by Study Arm	8; 1	—
PRIMARY Change in Cerebrospinal Fluid Amyloid Levels (pg/ml) Over 28 Day Intervention Period by Study Arm	57.1; 44.7	0.55
SECONDARY Change in Cerebrospinal Fluid P-tau Levels (pg/ml)	-5.7; 11.0	0.19
SECONDARY Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct)	1.4; -4.5	0.02 sig
SECONDARY Change in Cerebrospinal Fluid Clusterin Levels (pg/ml)	2610; 201	0.31

Eligibility Criteria

Inclusion Criteria

Men or women aged 65-90, inclusive.
English-speaking, to ensure compliance with cognitive testing and study visit procedures.
Female participants must not be pregnant or of childbearing potential, i.e. either surgically sterile or postmenopausal for > 1 year.
Stable medical condition for three months prior to screening visit, with no clinically significant abnormalities of hepatic, renal, and hematologic function defined as follows:
Platelets > 100,000
Serum creatinine ≤ 1.6 mg/dL
Liver function tests ≤ 1.5 upper limit of normal
No clinically significant abnormalities of other laboratory studies (blood counts, chemistry panel, urinalysis) as determined by the study physician
Stable medications for 4 weeks prior to screening visit.
Able to ingest oral medications.
No history of adverse drug reactions to VPA or similar agents.
Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests in the opinion of the study physician.
Not demented by Hachinski Ischemic Index (< 4).

Exclusion Criteria

Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder.
Major depression in past 12 months (DSM-IV criteria), major mental illness such as schizophrenia, or recent (in past 12 months) alcohol or substance abuse by history.
History of invasive cancer within the past two years (excluding non-melanoma skin cancer).
Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000, anticoagulant treatment, major structural abnormality or sepsis in the area of the lumbosacral spine that would make spinal fluid collection technically difficult).
Clinically significant MRI abnormalities that contraindicate lumber or suggest central nervous system disease processes that could influence study outcomes in the opinion of the PI.
Use of any investigational agents within 30 days prior to screening.
Major surgery within eight weeks prior to the Baseline Visit.
Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart failure (New York Heart Association Class III or IV) .
Antiretroviral therapy for human immunodeficiency virus (HIV).
Residence in a skilled nursing facility.
Blindness, deafness, language difficulties or any other disability which may prevent the participant from participating or cooperating in the protocol.

Excluded Medications

Experimental drugs
Lamictal
Tricyclic antidepressants (amitriptyline/nortryptiline)
Carbamazepine/ oxcarbazepine
Benzodiazepines
Phenobarbital
Phenytoin
Tolbutamide
Topiramate
Warfarin
Zidovudine

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01729598). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.