Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00043849

Collaborator

(none)

Enrollment

Locations

Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary aim of this study is to determine the safety and efficacy of quetiapine (Seroquel) for the treatment of psychosis and/or agitation in patients with primary dementia complicated by coexistent parkinsonism, or patients with Parkinson's disease with dementia [PDD] who have episodes of agitation or psychosis. The secondary aim is to determine the safety and tolerability, particularly the influence on parkinsonism, of quetiapine when used to treat psychosis and/or agitation in patients with dementia complicated by coexistent parkinsonism.

Condition or Disease	Intervention/Treatment	Phase
Dementia Parkinson Disease	Drug: Quetiapine	Phase 4

Detailed Description

Psychosis and agitation often occur in the course of dementia and are a major source of patient disability and caregiver stress. For the common situation in which extrapyramidal (parkinsonian) motor dysfunction accompanies dementia, there is a therapeutic dilemma since the most frequently used drugs to treat the behavioral problems, neuroleptic antipsychotics, can worsen parkinsonism and have been associated with severe extrapyramidal reactions in some types of dementia. To date, the efficacy and tolerability of a promising alternative medication class to treat psychosis and agitation, namely atypical antipsychotics, has not been tested in patients with a primary dementia selected for coexisting parkinsonism.

This is a multicenter double-blind, controlled clinical trial in which 60 subjects with a primary dementia (probable Alzheimer's disease [AD] or probable dementia with Lewy bodies [DLB]) and coexisting parkinsonism, or Parkinson's disease with dementia [PDD] will be randomized to 1 of 2 treatment groups: (1) quetiapine (QUET); an atypical antipsychotic with a favorable extrapyramidal side effect profile), or (2) placebo. Each subject participates in the trial for 10 weeks and systematic ratings of behavior, motor function, cognition, adverse events and other outcomes occur at baseline and after 6 and 10 weeks of assigned treatment.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)

Study Start Date :

Jul 1, 2002

Actual Primary Completion Date :

Jun 1, 2005

Actual Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Fluent in English or Spanish.
Presence of dementia as defined by the Diagnostic and Statistical Manual of Psychiatry, 4th ed. (DSM-IV) American Psychiatric Association. 1994.
Meets NINDS/ADRDA diagnostic criteria for probable Alzheimer's disease [AD] or Consortium diagnostic criteria for probable dementia with Lewy bodies [DLB] or diagnostic criteria for Parkinson's disease with dementia [PDD].
Presence of psychosis and/or agitation that interferes with daily activities: a) psychosis, b) hallucination, c) delusion, or d) agitation.
Presence of 2 or more of the following extrapyramidal motor features: a) resting tremor, b) bradykinesia, c) limb rigidity, d) shuffling, short-stepped gait.
Sum of ratings for the resting tremor, bradykinesia, rigidity and gait items of the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination component must be greater than or equal to 2.
Brief Psychiatric Rating Scale (BPRS) score greater than or equal to 12.
Informed consent by participant or an appropriate proxy.
Spouse/caregiver who is willing and able to accompany the subject to all clinic visits.
A stable dosage of non-excluded medications for at least 2 weeks prior to the Screening Visit.
Is in a stable medical condition for at least 4 weeks prior to the Screening Visit.
Physically acceptable for this study as confirmed by medical history, physical exam and clinical laboratory tests.
Must be able to ingest oral medications.
Supervision must be available for administration of study medication.
Taking any marketed cholinesterase inhibitor (donepezil [Aricept], rivastigmine [Exelon], galantamine [Reminyl], tacrine [Cognex], and/or memantine at a dose unchanged for at least 2 weeks prior to the screening visit.
Participants may reside in their own home or in a supervised care setting, such as a nursing home.

Exclusion Criteria:

Mini Mental Status Examination Score <8.
Use of any of the following in the 3 weeks prior to the screening visit: (a) a neuroleptic or atypical antipsychotic medication; or (b) an anticholinergic drug, amantadine for the treatment of parkinsonism [treatment with levodopa (Sinemet, Sinemet CR) and any dopamine agonist, selegiline or entacapone is allowed].
A history of a severe adverse reaction to any antipsychotic medication.
A serious medical illness that would preclude the safe administration of quetiapine, including active cancer. Skin tumors other than malignant melanoma are not exclusionary. Patients with stable prostate cancer may be included at the discretion of the Program Director.
Current evidence or history in the last 2 years of epilepsy, focal brain lesion, head injury with loss of consciousness and/or immediate confusion after the injury.
Known pregnancy.

Excluded Medications During the Study:

Any classical neuroleptic antipsychotic, such as haloperidol (Haldol).
Any atypical antipsychotic, such as risperidone (Risperidal), quetiapine (Seroquel), ziprasidone (Geodon), olanzapine (Zyprexa) and clozapine (Clozaril).
Any anxiolytic other than lorazepam (Ativan), as described above. This includes clonazepam (Klonopin), diazepam (Valium), oxazepam (Serax), clorazepate (Tranxene), buspirone (Buspar) and hydroxyzine (Vistaril).
Any hypnotic other than lorazepam (Ativan), as described above. This includes estazolam (Prosom), flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), triazolam (Halcion), diphenhydramine (Benadryl), doxylamine (Unisom), zolpidem (Ambien), zaleplon (Sonata) and chloral hydrate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham, Alzheimer's Disease Research Center	Birmingham	Alabama	United States	35233-0017
2	University of California, San Diego, Alzheimer's Disease Center	La Jolla	California	United States	92037
3	VA Healthcare System Long Beach	Long Beach	California	United States	90822
4	University of California at Los Angeles, Alzheimer's Disease Center	Los Angeles	California	United States	90095-1769
5	Stanford/VA Aging Clinical Research Center, Department of Psychiatry & Behavioral Sciences	Palo Alto	California	United States	94304
6	Emory University, Alzheimer's Disease Center	Atlanta	Georgia	United States	30322
7	Medical College of Georgia	Augusta	Georgia	United States	30912
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	Southern Illinois University, School of Medicine	Springfield	Illinois	United States	62702
10	E. N. Rogers Memorial Veterans Hospital	Bedford	Massachusetts	United States	01730
11	University of Nevada	Las Vegas	Nevada	United States	89102
12	Parkinson's Disease and Movement Disorders Center, Albany Medical College	Albany	New York	United States	12205
13	Maimonides Medical Center	Brooklyn	New York	United States	11219
14	Columbia University, Alzheimer's Disease Research Center	New York	New York	United States	10032
15	University of Rochester Medical Center, Alzheimer's Disease Center	Rochester	New York	United States	14620
16	Syracuse VA Medical Center	Syracuse	New York	United States	13210
17	University of Pittsburgh, Alzheimer's Disease Research Center	Pittsburgh	Pennsylvania	United States	15213-2593
18	University of Texas Southwestern Medical Center at Dallas, Alzheimer's Disease Center	Dallas	Texas	United States	75390-9070
19	Memory Clinic at Southwestern Vermont Medical Center	Bennington	Vermont	United States	05201
20	Fletcher Allan Health Care, Inc.	Burlington	Vermont	United States	05401
21	University of Washington at Seattle, Alzheimer's Disease Research Center	Seattle	Washington	United States	98108-1597