Official Title: “Depakote ER vs. Seroquel for Agitated Behaviors in Nursing Home Care Unit Patients With Dementia”

The primary objective of the study is to assess the relative efficacy of Depakote ER and Seroquel for agitated behaviors among veterans with a dementia diagnosis residing in a Department of Veterans Affairs (VA) nursing home care unit (NHCU). The secondary objective of the study is to assess the relative tolerability of Depakote ER and Seroquel in this population. The primary hypothesis is that agitated dementia patients will demonstrate a significantly greater reduction in Cohen-Mansfield Agitation Inventory (CMAI) scores while treated with Depakote ER compared to treatment with Seroquel.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

This study is a prospective, single-center, randomized, double-blind, double-dummy, crossover trial of Depakote ER vs. Seroquel for agitated behaviors among veterans with dementia. After consent is obtained and after a washout period of one week or five half-lives after taper (if necessary), 20 eligible patients will be randomized to received one of two treatments. The first is DEPAKOTE ER, initiated at 250 mg daily. The other treatment will be Seroquel, starting at 25 mg BID. Both treatments will be co-administered with a placebo that matches the other drug (to preserve blinding). Using serial examinations and blinded laboratory reporting, doses will be adjusted to clinical response or to achieve a serum valproate level of at least 50 mcg/mL. After a treatment period of six weeks, patients will be crossed over to the other treatment without washout (doses will be adjusted concurrently) for a second six-week treatment period. The Cohen-Mansfield Agitation Inventory (CMAI) will be the primary outcome measure. Secondary measures include the Behavior Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD); Clinical Global Impression Scale – Severity; Clinical Global Impression Scale – Improvement; Barnes Akathisia Scale (BAS); and the Abnormal Involuntary Movements Scale (AIMS). Outcome measures will be performed at the end of each six-week treatment period to avoid carryover effects.

Intervention(s) in this Clinical Trial

• Drug: Depakote ER
• Drug: Seroquel

Primary Measures

• The primary objective of the study is to assess the relative efficacy of Depakote ER and Seroquel for agitated behaviors among veterans with a dementia diagnosis residing in a VA nursing home care unit (NHCU).

Secondary Measures

• The secondary objective of the study is to assess the relative tolerability of Depakote ER and Seroquel in this population.

Inclusion Criteria:

• Veterans
• Males or females
• Aged 55 or older
• With a diagnosis of dementia (either Alzheimer’s disease, vascular dementia, or mixed
• Alzheimer’s and vascular dementia)
• Residing in a Tuscaloosa VA Medical Center (TVAMC) NHCU bed
• Admitted to a NHCU bed at Tuscaloosa VA Medical Center
• Score of > 5 on the Functional Assessment Staging (FAST) scale
• Score of < 23 on the Mini-Mental State Examination
• Score of > 1 on the Behavior Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) global rating
• Total BEHAVE-AD score of > 8
• Agitation present (by history or chart review) for at least two weeks (to minimize chance of enrolling for agitation due to delirium).

Exclusion Criteria:

• Diagnosis of dementia caused by a condition other than either Alzheimer’s disease, vascular dementia, or mixed Alzheimer’s and vascular dementia
• History of schizophrenia, bipolar disorder, or schizoaffective disorder
• Untreated depressive or anxiety disorder
• Untreated pain evident on physical examination
• Known allergy or hypersensitivity to either study drug
• History of epilepsy or seizures
• Diagnosis of liver disease or significant abnormalities on liver function tests
• Thrombocytopenia
• Diagnosis or past history of pancreatitis
• Past history of neuroleptic malignant syndrome
• Co-morbid condition that would render tapering off of current antipsychotics or anticonvulsants unsafe
• History of agitation unresponsive to an adequate previous trial of either valproate or quetiapine
• The patient has no identifiable guardian, decision-making proxy, or next of kin to approach for consent to participate.
• The patient’s guardian, decision-making proxy, or next of kin withholds, or does not grant, consent to participate
• Patient judged to be too ill to participate

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 55 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Tuscaloosa Research & Education Advancement Corporation

Overall Clinical Trial Officials and Contacts

John L Shuster, MD Principal Investigator Tuscaloosa VA Medical Center  

Overall Contact: John L Shuster, MD (205) 554-2000 John.Shuster@med.va.gov

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00315900

Study ID Number: TREAC00081

ClinicalTrials.gov Identifier: NCT00315900

Health Authority: United States: Institutional Review Board