Clinical trial NCT00043849: Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
Official title: Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dementia
Parkinson Disease
Keywords: Psychosis
Agitation, Psychomotor
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
First posted: 2002-08-15
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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), 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Alzheimer's Disease Research Center
state: Alabama
city: La Jolla
country: United States
facility: University of California, San Diego, Alzheimer's Disease Center
state: California
city: Long Beach
country: United States
facility: VA Healthcare System Long Beach
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles, Alzheimer's Disease Center
state: California
city: Palo Alto
country: United States
facility: Stanford/VA Aging Clinical Research Center, Department of Psychiatry & Behavioral Sciences
state: California
city: Atlanta
country: United States
facility: Emory University, Alzheimer's Disease Center
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University, School of Medicine
state: Illinois
city: Bedford
country: United States
facility: E. N. Rogers Memorial Veterans Hospital
state: Massachusetts
city: Las Vegas
country: United States
facility: University of Nevada
state: Nevada
city: Albany
country: United States
facility: Parkinson's Disease and Movement Disorders Center, Albany Medical College
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: Columbia University, Alzheimer's Disease Research Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center, Alzheimer's Disease Center
state: New York
city: Syracuse
country: United States
facility: Syracuse VA Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Alzheimer's Disease Research Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas, Alzheimer's Disease Center
state: Texas
city: Bennington
country: United States
facility: Memory Clinic at Southwestern Vermont Medical Center
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allan Health Care, Inc.
state: Vermont
city: Seattle
country: United States
facility: University of Washington at Seattle, Alzheimer's Disease Research Center
state: Washington
Study officials:
affiliation: University of Rochester Medical Center, Department of Neurology
name: Roger Kurlan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cummings JL, Knopman D. Advances in the treatment of behavioral disturbances in Alzheimer's disease. Neurology. 1999 Sep 22;53(5):899-901. doi: 10.1212/wnl.53.5.899. No abstract available.
citation: 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. doi: 10.1016/s0140-6736(05)78999-6. No abstract available.
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.