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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00043849
• Other study ID #: IA0034
• Status: Completed
• Phase: Phase 4
• First received: August 14, 2002
• Last updated: December 10, 2009
• Start date: July 2002
• Est. completion date: June 2005

Study information

• Verified date: August 2006
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dementia
• Parkinson Disease
• Parkinsonian Disorders

Intervention

Drug:
• Quetiapine

Locations

Country	Name	City	State
United States	Parkinson's Disease and Movement Disorders Center, Albany Medical College	Albany	New York
United States	Emory University, Alzheimer's Disease Center	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	E. N. Rogers Memorial Veterans Hospital	Bedford	Massachusetts
United States	Memory Clinic at Southwestern Vermont Medical Center	Bennington	Vermont
United States	University of Alabama at Birmingham, Alzheimer's Disease Research Center	Birmingham	Alabama
United States	Maimonides Medical Center	Brooklyn	New York
United States	Fletcher Allan Health Care, Inc.	Burlington	Vermont
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Texas Southwestern Medical Center at Dallas, Alzheimer's Disease Center	Dallas	Texas
United States	University of California, San Diego, Alzheimer's Disease Center	La Jolla	California
United States	University of Nevada	Las Vegas	Nevada
United States	VA Healthcare System Long Beach	Long Beach	California
United States	University of California at Los Angeles, Alzheimer's Disease Center	Los Angeles	California
United States	Columbia University, Alzheimer's Disease Research Center	New York	New York
United States	Stanford/VA Aging Clinical Research Center, Department of Psychiatry & Behavioral Sciences	Palo Alto	California
United States	University of Pittsburgh, Alzheimer's Disease Research Center	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center, Alzheimer's Disease Center	Rochester	New York
United States	University of Washington at Seattle, Alzheimer's Disease Research Center	Seattle	Washington
United States	Southern Illinois University, School of Medicine	Springfield	Illinois
United States	Syracuse VA Medical Center	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ballard C, Grace J, McKeith I, Holmes C. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer's disease. Lancet. 1998 Apr 4;351(9108):1032-3. — View Citation

Cummings JL, Knopman D. Advances in the treatment of behavioral disturbances in Alzheimer's disease. Neurology. 1999 Sep 22;53(5):899-901. — View Citation

McManus DQ, Arvanitis LA, Kowalcyk BB. Quetiapine, a novel antipsychotic: experience in elderly patients with psychotic disorders. Seroquel Trial 48 Study Group. J Clin Psychiatry. 1999 May;60(5):292-8. — View Citation