Apathy Associated With Alzheimer's Disease - Full Text View

Sponsors and Collaborators:	Sunnybrook Health Sciences Centre American Health Assistance Foundation
Information provided by:	Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:	NCT00254033

Purpose

Apathy, or lack of motivation, affects up to 80% of Alzheimer's disease (AD) patients. These amotivational symptoms increase patient reliance on caregivers, increase caregiver burden and distress, and increase the risk of patient institutionalization. Only 50% of patients with apathy respond to current treatment with cholinesterase inhibitors. The mechanism of apathy in AD is unknown hampering rational treatment. Our proposed pilot study will provide initial data required to develop an amphetamine challenge paradigm to probe the brain reward system. These results will be used to develop a larger study evaluating the role of the brain reward system in apathy in AD and link this information with pharmacologic treatment. AD is a complex neurobiological illness that needs to be understood at several levels to optimize treatment. At a neurochemical level, one has to identify the neurotransmitter abnormalities that accompany the clinical symptoms. The neurochemical level of analysis provides the link between pathology and symptoms and, for now, is the only avenue for biological therapies. Next, one has to translate knowledge of neurochemical abnormalities to practical treatments for the symptoms of AD. This pilot will allow us to develop a study that can address both of these goals. Furthermore, the larger study will further define the emerging concept of apathy as a syndrome and has broader implications for apathy in many other neuropsychiatric diseases.

Condition	Intervention	Phase
Dementia Alzheimer Disease	Drug: Dextroamphetamine Drug: Methylphenidate	Phase IV

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Caregivers Alzheimer's Disease Caregivers Dementia

Drug Information available for: Methylphenidate hydrochloride Methylphenidate Dopamine Dopamine hydrochloride Dextroamphetamine Dextroamphetamine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	The Role of the Dopaminergic Brain Reward System in Apathy Associated With Alzheimer's Disease

Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:

Addiction Research Centre Inventory (ARCI)
Apathy Evaluation Scale-Caregiver (AES-C)

Secondary Outcome Measures:

Profile of Mood States (POMS)
Continuous Performance Test (CPT)
Neuropsychiatric Inventory (NPI)

Estimated Enrollment:	40
Study Start Date:	October 2003
Study Completion Date:	October 2006

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age > 55 years
meet DSM-IV criteria for primary degenerative dementia
meet NINCDS-ARDA criteria for probable Alzheimer's Disease of at least one year's duration
mild to moderate cognitive impairment (Global Deterioration Scale GDS <6, Mini-Mental State Examination >10
on a stable dose of a cholinesterase inhibitor for at least 3 months
apathetic group only: Neuropsychiatric Inventory (NPI) Apathy subscale score >=2

Exclusion Criteria:

abnormal biochemical screening: blood cell count, vitamin B12, thyroid function tests, and syphilis screening tests
significant medical illness or other medical/neurological conditions which diminish cognitive function
evidence of seizure disorder
an Hachinski ischemic score >3 indicating vascular dementia
a brain computed tomographic (CT) scan revealing focal lesions, or inconsistent with AD
electrocardiographic, laboratory or physical evidence of significant cardiovascular disease
presence of premorbid or current psychiatric diagnosis including: major depression, schizophrenia, psychotic symptoms of a severity likely to provoke violent or dangerous behaviour (i.e., command hallucinations to harm people or persecutory delusions that provoke violent reactions)
current or past psychoactive substance abuse or dependence (including alcohol, excluding nicotine)
contraindications to receiving dextroamphetamine or methylphenidate
have had administration of a depot neuroleptic injection within one treatment cycle of the first visit

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00254033

Locations

Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

American Health Assistance Foundation

Investigators

Principal Investigator:

Krista L Lanctot, PhD

Sunnybrook Health Sciences Centre

More Information

Study ID Numbers:	065-2003, AHAF Grant Number: A2003-236
Study First Received:	November 10, 2005
Last Updated:	May 21, 2008
ClinicalTrials.gov Identifier:	NCT00254033
Health Authority:	Canada: Health Canada

Keywords provided by Sunnybrook Health Sciences Centre:

Alzheimer's Disease
Apathy
Brain Reward System

Dopamine
Dextroamphetamine Challenge
Methylphenidate

Study placed in the following topic categories:

Dopamine
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dextroamphetamine
Alzheimer Disease
Methylphenidate

Central Nervous System Diseases
Neurodegenerative Diseases
Brain Diseases
Dementia
Cognition Disorders
Delirium

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Physiological Effects of Drugs

Nervous System Diseases
Central Nervous System Stimulants
Dopamine Agents
Tauopathies
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009