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

NCT01729598 | Completed Early Phase 1 Results

• 1 other identifier: 12-0068-F6A
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Keywords

cognitively normal elderly population; safety and tolerability

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  Baseline and day 28

Secondary Outcomes (3)

• Change in Cerebrospinal Fluid P-tau Levels (pg/ml)

  Baseline and day 28

• Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct)

  Baseline and day 28

• Change in Cerebrospinal Fluid Clusterin Levels (pg/ml)

  Baseline and day 28

Study Arms (2)

Valproic Acid

EXPERIMENTAL

Valproic acid 250 mg or 500mg by mouth twice daily.

Drug: Valproic Acid

Placebo

PLACEBO COMPARATOR

Placebo capsule by mouth twice daily.

Drug: Placebo

Interventions

Valproic Acid DRUG

generic valproic acid tablets packaged in placebo-matched capsules.

Also known as: VPA, Depakote

Valproic Acid

Placebo DRUG

Placebo capsule without active study medication in identical capsules as experimental medicine.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gregory Jicha, 323-5550: lead
• University of Kentucky: collaborator
• Kentucky Alzheimer's Center: collaborator

Study Sites (1)

Sander's Brown Center on Aging

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Valproic Acid; Sugars

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Carbohydrates

Results Point of Contact

• Title: Dr. Gregory A. Jicha
• Organization: University of Kentucky

gregory.jicha@uky.edu

859-323-5550

Study Officials

• Steve Estus, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Gregory Jicha, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: November 20, 2012
• Study Start: April 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 9, 2019
• Results First Posted: October 9, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 1/1/19 to 12/31/28
• Access Criteria: Access will be granted to any investigator upon provision of an acceptable project hypothesis and specification of data desired. Oversight by the project team will ensure that redundant projects do not result in competitive use of the resources. Project data access will be determined by the PI and investigator team at UK within these broad access terms. There will be no cost for data access. We stipulate that the parent grant UL1TR001998 should be cited by those with whom data is shared.

Locations

US (1)