Depakote Extended Release (ER) Versus Seroquel for Agitated Behaviors in Nursing Home Care Unit Patients With Dementia

Sponsor

Tuscaloosa Research & Education Advancement Corporation (Other)

Overall Status

Terminated

CT.gov ID

NCT00315900

Collaborator

Abbott (Industry)

Enrollment

Location

Arms

21.9

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Agitation Dementia	Drug: Depakote ER Drug: Seroquel	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Depakote ER vs. Seroquel for Agitated Behaviors in Nursing Home Care Unit Patients With Dementia

Actual Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Feb 28, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Depakote ER Depakote ER	Drug: Depakote ER depakote ER Other Names: Divalproex
Active Comparator: Seroquel Seroquel	Drug: Seroquel seroquel Other Names: quetiapine

Arm

Intervention/Treatment

Experimental: Depakote ER

Depakote ER

Drug: Depakote ER

depakote ER

Other Names:

Divalproex

Active Comparator: Seroquel

Seroquel

Drug: Seroquel

seroquel

Other Names:

quetiapine

Outcome Measures

Primary Outcome Measures

Cohen-Mansfield Agitation Inventory (CMAI) [12 week]
Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale to systematically assess agitation (higher is more severe).

Secondary Outcome Measures

Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) [12 weeks]
A psychiatric rating scale to evaluate behavioral disturbances in dementia patients. assesses 25 potentially remediable behavioral symptoms on a 4-rating-point severity scale (higher score is more severe).

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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