Trial record 3 of 41 for:    University of Kentucky | Alzheimer's disease | United States, Kentucky

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Kentucky Alzheimer's Center
Information provided by (Responsible Party):
Gregory Jicha, 323-5550, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01729598
First received: May 14, 2012
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Alzheimer's Disease
Drug: Valproic Acid
Drug: Placebo
Phase 0

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 14
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)
Arms Assigned Interventions
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.
Other Names:
  • VPA
  • Depakote
Placebo Comparator: Placebo
Placebo capsule by mouth twice daily.
Drug: Placebo
Placebo capsule without active study medication in identical capsules as experimental medicine.
Other Name: Sugar pill

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   65 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men or women aged 65-90, inclusive.
  2. English-speaking, to ensure compliance with cognitive testing and study visit procedures.
  3. Female participants must not be pregnant or of childbearing potential, i.e. either surgically sterile or postmenopausal for > 1 year.
  4. 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
  5. Stable medications for 4 weeks prior to screening visit.
  6. Able to ingest oral medications.
  7. No history of adverse drug reactions to VPA or similar agents.
  8. Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests in the opinion of the study physician.
  9. Not demented by Hachinski Ischemic Index (< 4).

Exclusion Criteria:

  1. Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis or seizure disorder.
  2. 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.
  3. History of invasive cancer within the past two years (excluding non-melanoma skin cancer).
  4. 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).
  5. 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.
  6. Use of any investigational agents within 30 days prior to screening.
  7. Major surgery within eight weeks prior to the Baseline Visit.
  8. Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart failure (New York Heart Association Class III or IV) .
  9. Antiretroviral therapy for human immunodeficiency virus (HIV).
  10. Residence in a skilled nursing facility.
  11. Blindness, deafness, language difficulties or any other disability which may prevent the participant from participating or cooperating in the protocol.

Excluded Medications

  1. Experimental drugs
  2. Lamictal
  3. Tricyclic antidepressants (amitriptyline/nortryptiline)
  4. Carbamazepine/ oxcarbazepine
  5. Benzodiazepines
  6. Phenobarbital
  7. Phenytoin
  8. Tolbutamide
  9. Topiramate
  10. Warfarin
  11. Zidovudine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01729598

Locations
United States, Kentucky
Sander's Brown Center on Aging
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
University of Kentucky
Kentucky Alzheimer's Center
Investigators
Principal Investigator: Steve Estus, PhD University of Kentucky
Principal Investigator: Gregory Jicha, MD University of Kentucky
  More Information

No publications provided

Responsible Party: Gregory Jicha, 323-5550, Professor, University of Kentucky
ClinicalTrials.gov Identifier: NCT01729598     History of Changes
Other Study ID Numbers: 12-0068-F6A
Study First Received: May 14, 2012
Last Updated: January 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Kentucky:
cognitively normal elderly population
safety and tolerability

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Dementia
Tauopathies
Valproic Acid
Anticonvulsants
Antimanic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014