Alzheimer's DiseaseEarly Phase 1VPANCT01729598
Valproic Acid in Subjects With Intact Cognition - Proof of Concept Study
A Early Phase 1 study testing Valproic Acid in people with Alzheimer's Disease, run by Gregory Jicha, 323-5550 at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Valproic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Oct 2014
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 90 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Sander's Brown Center on Aging
Lexington, Kentucky, 40536
About this study
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
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.
Read the 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.
- Conditions
- Alzheimer's Disease
- Being tested
- Valproic Acid, Placebo
- Keywords
- cognitively normal elderly population, safety and tolerability
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Also called VPA, Depakote
generic valproic acid tablets packaged in placebo-matched capsules.
PlaceboDrug
Also called Sugar pill
Placebo capsule without active study medication in identical capsules as experimental medicine.
| Study group | Role | What they receive |
|---|---|---|
| Valproic Acid | Experimental | Valproic acid 250 mg or 500mg by mouth twice daily. Receives: Drug: Valproic Acid |
| Placebo | Placebo comparator | Placebo capsule by mouth twice daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: Baseline and day 28
Secondary outcomes (3)
Change in Cerebrospinal Fluid P-tau Levels (pg/ml)
Change in cerebrospinal fluid p181-tau levels (pg/ml) from baseline to end of treatment (Day 28)
Measured: Baseline and day 28
Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct)
Change in Free \& Cued Selective Reminding Test- delayed free recall from baseline to end of treatment (Day 28)
Measured: Baseline and day 28
Change in Cerebrospinal Fluid Clusterin Levels (pg/ml)
Change in cerebrospinal fluid clusterin levels (pg/ml) from baseline to end of treatment (Day 28)
Measured: Baseline and day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startApr 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory Jicha, 323-5550
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kentucky, Kentucky Alzheimer's Center
- Responsible party
- Sponsor-investigator, Gregory Jicha, 323-5550, University of Kentucky
- Investigators
- Steve Estus, PhD, Principal investigator, University of KentuckyGregory Jicha, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01729598
- Sponsor's protocol ID
- 12-0068-F6A
- Acronym
- VPA
- Status last verified
- Oct 2019
- First submitted
- 14 May 2012
- Last updated
- 9 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD will be shared with interested investigators that submit a data request to the UK Alzheimer Center Biostatistics Group upon publication of the primary manuscript from this study. The request will be reviewed for scientific validity and human subjects protection issues prior to approval for release. IPD that may be released includes all clinical data stripped of identifying information. Clinical Information will be assigned a blinded subject number that protects the identity and HIPAA protected information collected as part of this study. To request data, follow the instructions at the following link: http://www.uky.edu/coa/adc/investigators-research-resources
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01729598
- Acronym / sponsor ID
- VPA / 12-0068-F6A
- Conditions
- Alzheimer's Disease
- Keywords
- cognitively normal elderly population, safety and tolerability
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Gregory Jicha, 323-5550University, hospital or other
- Collaborators
- University of Kentucky, Kentucky Alzheimer's Center
- Study start
- Apr 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 20 Nov 2012 (estimated)
- Results
- Posted 9 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valproic Acid | Experimental | Drug: Valproic AcidValproic acid 250 mg or 500mg by mouth twice daily. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsule by mouth twice daily. |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (13 listed)
- 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:
- Stable medications for 4 weeks prior to screening visit.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic AcidAlso: VPA, Depakotegeneric valproic acid tablets packaged in placebo-matched capsules. | Drug | Valproic Acid |
| PlaceboAlso: Sugar pillPlacebo capsule without active study medication in identical capsules as experimental medicine. | Drug | Placebo |
Primary outcome
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)
3 secondary outcomes
Change in Cerebrospinal Fluid P-tau Levels (pg/ml)
Time frame: Baseline and day 28
Change in Free & Cued Selective Reminding Test- Free Recall (Number of Items Correct)
Time frame: Baseline and day 28
Change in Cerebrospinal Fluid Clusterin Levels (pg/ml)
Time frame: Baseline and day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD will be shared with interested investigators that submit a data request to the UK Alzheimer Center Biostatistics Group upon publication of the primary manuscript from this study. The request will be reviewed for scientific validity and human subjects protection issues prior to approval for release. IPD that may be released includes all clinical data stripped of identifying information. Clinical Information will be assigned a blinded subject number that protects the identity and HIPAA protected information collected as part of this study. To request data, follow the instructions at the following link: http://www.uky.edu/coa/adc/investigators-research-resources
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steve Estus, PhD principal investigator
University of Kentucky
Gregory Jicha, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Valproic Acid in people with Alzheimer's Disease, run by Gregory Jicha, 323-5550 at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Adverse Events Over the Duration of the Study by Study Arm (time frame: Day 35). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2019.