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	Treatment or Intervention	Phase
Dementia Parkinson Disease	Drug: Quetiapine	Phase IV

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.

Ages Eligible for Study:  50 Years and above,  Genders Eligible for Study:  Both

Criteria

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), clozazepate (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.

Cheryl Deeley      585-341-7500    cdeeley@mct.rochester.edu

Alabama
      University of Alabama at Birmingham, Alzheimer's Disease Research Center, Birmingham,  Alabama,  35233-0017,  United States; Recruiting
Arizona
      Arizona Health Sciences Center, Tucson,  Arizona,  85724-5023,  United States; Recruiting
California
      University of California at Los Angeles, Alzheimer's Disease Center, Los Angeles,  California,  90095-1769,  United States; Recruiting
      University of California, San Diego, Alzheimer's Disease Center, La Jolla,  California,  92037,  United States; Recruiting
      VA Healthcare System Long Beach, Long Beach,  California,  90822,  United States; Recruiting
      Stanford/VA Aging Clinical Research Center, Department of Psychiatry & Behavioral Sciences, Palo Alto,  California,  94304,  United States; Recruiting
Georgia
      Emory University, Alzheimer's Disease Center, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      Rush University Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
      Southern Illinois University, School of Medicine, Springfield,  Illinois,  62702,  United States; Recruiting
Massachusetts
      E. N. Rogers Memorial Veterans Hospital, Bedford,  Massachusetts,  01730,  United States; Recruiting
Nevada
      University of Nevada, Las Vegas,  Nevada,  89102,  United States; Recruiting
New York
      Columbia University, Alzheimer's Disease Research Center, New York,  New York,  10032,  United States; Recruiting
      Maimonides Medical Center, Brooklyn,  New York,  11219,  United States; Recruiting
      University of Rochester Medical Center, Alzheimer's Disease Center, Rochester,  New York,  14620,  United States; Recruiting
      Parkinson's Disease and Movement Disorders Center, Albany Medical College, Albany,  New York,  12205,  United States; Recruiting
      Syracuse VA Medical Center, Syracuse,  New York,  13210,  United States; Recruiting
Pennsylvania
      University of Pittsburgh, Alzheimer's Disease Research Center, Pittsburgh,  Pennsylvania,  15213-2593,  United States; Recruiting
Texas
      University of Texas Southwestern Medical Center at Dallas, Alzheimer's Disease Center, Dallas,  Texas,  75390-9070,  United States; Recruiting
Vermont
      Fletcher Allan Health Care, Inc., Burlington,  Vermont,  05401,  United States; Recruiting
      Memory Clinic at Southwestern Vermont Medical Center, Bennington,  Vermont,  05201,  United States; Recruiting
Washington
      University of Washington at Seattle, Alzheimer's Disease Research Center, Seattle,  Washington,  98108-1597,  United States; Recruiting

Study chairs or principal investigators

Roger Kurlan, MD,  Principal Investigator,  University of Rochester Medical Center, Department of Neurology   

Study ID Numbers:  IA0034
Record last reviewed:  November 2004
Record first received:  August 14, 2002
ClinicalTrials.gov Identifier:  NCT00043849
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-17