Phase 3
N=313
Valproate in Dementia (VALID)
Alzheimer Disease
Bottom Line
View on ClinicalTrials.gov: NCT00071721 ↗Enrolled (actual)
313
Serious AEs
36.1%
Results posted
Oct 2010
Primary outcome: Primary: Presence of Agitation and/or Psychosis Measured by the Neuropsychiatric Inventory (NPI) Combined With an Assessment of the Clinical Significance of Behavioral Change Rated by the Study Clinician — 25; 29 Participants — p=0.88
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Valproate (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- Alzheimer's Disease Cooperative Study (ADCS)
- Primary completion
- Feb 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Presence of Agitation and/or Psychosis Measured by the Neuropsychiatric Inventory (NPI) Combined With an Assessment of the Clinical Significance of Behavioral Change Rated by the Study Clinician |
25; 29 | 0.88 |
| SECONDARY Cognitive Performance Assessed by the Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog) |
42.3; 41.9 | — |
| SECONDARY Functional Performance Assessed by the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory |
35.1; 41.0 | — |
| SECONDARY Global Severity of Dementia Using the CDR Sum of Boxes |
12.0; 11.5 | — |
| SECONDARY Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version |
10.6; 12.1 | — |
| SECONDARY Participant's Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC) |
5.7; 5.5 | — |
Summary
The purpose of this trial is to demonstrate whether valproate therapy delays the emergence of agitation and/or psychosis in outpatients with probable Alzheimer's disease (AD) who have not experienced agitation and psychosis in their illness. A secondary aim is to determine whether valproate therapy delays the progression of cognitive and functional measures of the illness. This trial will also assess the tolerability and safety of low-dose, long-term valproate therapy. Valproate, an anticonvulsant drug, was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD.
Eligibility Criteria
Inclusion Criteria
- Probable AD by National Institute of Neurological Disorders and Stroke (NINDS)-Alzheimer's Disease and Related Disorder Association (ADRDA) criteria.
- Males or females.
- > 55 and 40 kg (88.2 lbs.).
- Residing in the community at Screen and Baseline. Participants may reside in assisted living facilities, but not in long-term care nursing facilities or assisted living facilities that provide intensive support for people with dementia nor may they reside in a secure unit necessary for behavioral management.
- Mini Mental State Examination (MMSE) at Screen and Baseline 12-20 inclusive.
- Computed tomography (CT) or magnetic resonance imaging (MRI) since onset of dementia consistent with the diagnosis of probable AD. Single lacunes in non-critical areas and non-specific white matter changes that are interpreted as age-related are not grounds for exclusion. Any ambiguous scan results must be reviewed with the Project Director.
- Fluent in English or Spanish.
- Supervision available for study medication.
- Study partner to accompany subject to all visits.
- Study partner must have in-person contact with the participant > 2 days/week.
- Able to ingest oral medication.
- Total Neuropsychiatric Inventory (NPI) score for previous 4 weeks 1.2 or partial thromboplastin time (PTT) > 40 seconds.
- Active neoplastic disease. Exceptions: skin tumors other than melanoma are not excluded; patients with stable prostate cancer may be included at the discretion of the Project Director; women who have been treated for breast cancer and have no metastases and whose survival is expected to exceed 2 years may be considered for inclusion on a case-by-case basis in consultation with the Project Director; patients with purely localized bladder wall cancers may be included at the discretion of the Project Director.
Excluded Medications:
- Use of psychotropics for treatment of agitation or psychosis. Antidepressants used in stable doses for 3 months prior to Screening to treat depression or anxiety, but not agitation, will be permitted. Low dose sedatives for sleep, but not agitation, will be permitted. Cholinesterase inhibitors used in stable doses for at least 3 months prior to Screening are permitted.
- Regular use of narcotic analgesics within 3 months of Screening.
- Anti-parkinsonian medications (e.g. levodopa, selegiline, pergolide, bromocriptine, pramipexole) within 2 months of Screening.
- Use of drugs with significant central anticholinergic or antihistaminic effects (eg, benztropine, trihexyphenidyl, dicyclomine, diphenhydramine, cyproheptadine, diphenoxylate, hydroxyzine, meclizine, prochlorperazine, promethazine) within 2 months of Screening.
- Use of other investigational drug studies within two months prior to Screening.
- Use of other anticonvulsants within 5 years prior to Screening.
- Use of zidovudine at any time.
- Use of tricyclic antidepressants within 1 month prior to Screening.
- Regular use of high doses of salicylates at Screening (> 1,300 mg/d).
- Vitamin E > 2, 100 IU/d within 1 month prior to Screening.
- Warfarin use is permitted when approved by the Project Director and INR and PTT criteria are met.
Data sourced from ClinicalTrials.gov (NCT00071721). 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.