CompletedPhase 3Results posted

Valproate in Dementia (VALID)

A Randomized, Double-Blind, Placebo-Controlled Trial of Valproate to Attenuate the Progression of Alzheimer's Disease (AD)

Lead sponsor

Alzheimer's Disease Cooperative Study (ADCS)

Asset

Valproate

Listed sites

Recruiting sites

Enrollment

313

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 12-20•Study partner/caregiver required

Primary endpoint

•Neuropsychiatric Inventory (NPI)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

SecondaryADCS Protocol ADC-022-VN

Org study IDIA0043

SecondaryIND 67,222

NCT IDNCT00071721

Timeline

Milestones

Study start2003-10 (month precision)

Study first posted2003-10-31estimated

Primary completion2009-02actual (month precision)

Study completion2009-12actual (month precision)

Results first posted2010-10-20estimated

Last update posted2014-09-25estimated

Assets

Drug assets

Valproate

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

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 < 90 years of age.

•Weight > 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 < 8 at Screening, and for the period between Screening and Baseline.

•NPI item score for the items assessing delusions, hallucinations, agitation/aggression all greater than or equal to 1 for 4 weeks prior to Screening (less than once/week and mild severity at most) and for the period between Screening and Baseline.

•Scores of greater than or equal to 1 for items rating delusions, hallucinations, and agitation/aggression taken from the NPI, modified to assess these features since onset of illness. This will be derived from a second interview with the modified NPI. (Agitation/psychosis during episodes of delirium are not considered exclusionary.)

Exclusion criteria

Exceptions to these criteria may be considered on a case-by-case basis at the discretion of the Project Director:

•Non-AD dementia.

•Females of child-bearing potential.

•Residence in a long-term care facility or equivalent at Baseline.

•Presence or previous history of agitation or psychosis requiring active psychotropic medication since the illness began.

•History of clinically significant stroke.

•Current evidence or history in past two years of: focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.

•Sensory impairment that would prevent subject from participating in or cooperating with the protocol.

•Medical contraindications to study participation.

•Use of another investigational agent within two months prior to Screening.

•Evidence of any significant clinical disorder or laboratory finding that renders the subject unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality.

•Clinical contraindication to the use of valproate (e.g., known hypersensitivity or allergic reactions, severe neutropenia, severe hepatic disease, or urea cycle disorder. A urea cycle disorder should be considered in patients with history of unexplained encephalopathy following protein meals, or family history of urea cycle disorder).

•History of seizure within past 5 years prior to Screening.

•Platelet count < 100,000/mm^3.

•International Normalized Ratio (INR) > 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.

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Behavior / neuropsychiatric

Function / daily living

Other clinical outcomes

Global cognition

4 endpoints

Secondary/protocol endpoint

Cognitive Performance Assessed by the Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog)

Time frame:24 months

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Global Severity of Dementia Using the CDR Sum of Boxes

Time frame:24 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

descriptive

Secondary/registry result

Cognitive Performance Assessed by the Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog)

Time frame:24 months

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Valproaten=153 Participants	42.3	14.3
Placebon=160 Participants	41.9	14.4

Secondary/registry result

Global Severity of Dementia Using the CDR Sum of Boxes

Time frame:24 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

descriptive

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Valproaten=153 Participants	12.0	4.1
Placebon=160 Participants	11.5	3.7

Function / daily living

2 endpoints

Secondary/protocol endpoint

Functional Performance Assessed by the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory

Time frame:24 months

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Secondary/registry result

Functional Performance Assessed by the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory

Time frame:24 months

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Valproaten=153 Participants	35.1	20.3
Placebon=160 Participants	41.0	14.81

Behavior / neuropsychiatric

4 endpoints

Primary/protocol endpoint

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

Time frame:24 months

Neuropsychiatric Inventory (NPI)

descriptive

Primary/registry result

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

Time frame:24 months

Neuropsychiatric Inventory (NPI)

descriptive

Posted result

Group	Value (number), Participants	Reported bounds
Valproaten=153 Participants	25	-
Placebon=160 Participants	29	-

Cox Proportional Hazard0.958p0.88Cox Proportional Hazards

Secondary/protocol endpoint

Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version

Time frame:24 months

event count, event

Secondary/registry result

Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version

Time frame:24 months

event count, event

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Valproaten=153 Participants	10.6	11.6
Placebon=160 Participants	12.1	10.9

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

Participant's Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)

Time frame:24 months

change from baseline, improvement

Secondary/registry result

Participant's Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)

Time frame:24 months

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Valproaten=153 Participants	5.7	0.9
Placebon=160 Participants	5.5	1.1

Publications (4)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.