Adjunctive Donepezil Therapy and Genetic Risk Factors of Cognitive Dysfunction in Brain Tumor Survivors - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center Weill Medical College of Cornell University
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00594633

Purpose

A significant number of brain tumor patients who received radiation or chemotherapy have thinking problems as a result of their treatment. The purpose of this study is to find out if treatment with Aricept (donepezil) may improve some aspects of thinking abilities in patients with brain tumors who received radiation or chemotherapy. This research will also study whether persons having particular genes for a blood-borne substance called apolipoprotein E (APOE) are more likely to have thinking problems after radiation or chemotherapy treatment for their brain tumors. The findings of this study will help us find out whether Aricept can improve thinking abilities after cancer treatment, and whether some of the thinking difficulties may be in part related to having certain genes.

Condition	Intervention
Brain Tumor Brain Cancer CNS Cancer Cognitive Dysfunction	Other: donepezil and questionaires

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Donepezil E 2020 BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	Adjunctive Donepezil Therapy and Genetic Risk Factors of Cognitive Dysfunction in Brain Tumor Survivors

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

The primary goal of this study is to assess the efficacy of donepezil in improving executive abilities and psychomotor speed in adult brain tumor patients who have undergone cranial irradiation and/or chemotherapy. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

This study will also assess the efficacy of donepezil in improving other cognitive domains such as attention, memory, and general cognition in this population. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
The study will also explore the possibility that the possession of the apolipoprotein E (APOE) є-4 allele is associated with the development of cognitive difficulties following cranial radiation and/or chemotherapy treatments. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2004
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental donepezil and questionaires	Other: donepezil and questionaires Patients will undergo a brief cognitive evaluation prior to (baseline/Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 2) ,Cognitive Re-Evaluation (about 6 months after discontinuation of Donepezil). Then pt will be tx with donepezil, an acetylcholinesterase inhibitor. They will undergo a four-week dose titration (i.e., 5mg QD during weeks 1-4) to reach a final dose of 10mg QD of oral donepezil there after for a maximum of 24 weeks.

Arms

Assigned Interventions

1: Experimental

donepezil and questionaires

Other: donepezil and questionaires

Patients will undergo a brief cognitive evaluation prior to (baseline/Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 1), Cognitive Re-Evaluation (about 12 weeks after Time 2) ,Cognitive Re-Evaluation (about 6 months after discontinuation of Donepezil). Then pt will be tx with donepezil, an acetylcholinesterase inhibitor. They will undergo a four-week dose titration (i.e., 5mg QD during weeks 1-4) to reach a final dose of 10mg QD of oral donepezil there after for a maximum of 24 weeks.

Detailed Description:

A significant proportion of brain tumor patients treated with radiation or chemotherapy who are in disease remission experience cognitive sequelae from their treatment. Cognitive dysfunction can be of sufficient severity to interfere with their ability to function at premorbid professional and social levels. There are, however, no approved pharmacological interventions for improving cognitive functions in cancer patients who display treatment-related cognitive deficits. Donepezil, an acetylcholinesterase inhibitor, has been shown to provide cognitive and functional benefits in patients with Alzheimer's disease, vascular dementia, and in patients with other neurological diseases without known cholinergic deficiency. The proposed pilot study will examine the efficacy of donepezil in improving cognitive functions in adult brain tumor patients treated with radiation and/or chemotherapy who have mild to moderate cognitive difficulties. Neuropsychological measures of executive, psychomotor speed, attention, and memory abilities will be administered prior to, during and following donepezil therapy. The proposed study will also test the hypothesis that the apolipoprotein E (APOE) e-4 allele correlates with the development of cognitive impairment after radiation or chemotherapy treatments. The proposed investigation is unprecedented and may provide preliminary information about (1) a pharmacological therapy that could improve cognitive functions in this population, and (2) a genetic risk factor that may increase vulnerability to radiation or chemotherapy-induced cognitive decline.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

diagnosed with a brain tumor and treated with cranial irradiation and/or chemotherapy, and in stable remission of their disease at the time of enrollment.
completed radiation and/or chemotherapy treatment at least 6 months prior to being enrolled in the study.
who obtain a Mini-Mental Status Examination (MMSE) score ranging from 18 to 28 at the time of enrollment.
are at least 18 years of age.
are English speaking.
have capacity to give consent

Exclusion Criteria:

Patients with active or progressive disease on recent MRI of the brain either at the time of enrollment, or during the study period.
with a pre-existing uncontrolled seizure disorder, or significant renal or hepatic impairment.
taking the following medications: antipsychotics, psychostimulants.
patients who have been on selective serotonin re-uptake inhibitors (SSRIs) for less than 3 months at the time of enrollment.
with uncontrolled behavioral or mood disturbances.
have their anticonvulsant medication(s) or dosage(s) changed less than 30 days prior to enrollment.
currently receiving donepezil or other cholinesterase inhibitors.
who is pregnant.
unable to cooperate or complete cognitive tests.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594633

Contacts

Contact: Denise Correa, PhD

corread@mskcc.org

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Denise Correa, PhD corread@mskcc.org
Principal Investigator: Denise Correa, PhD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Weill Medical College of Cornell University

Investigators

Principal Investigator:

Denise Correa, PhD

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Denise Correa, PhD )
Study ID Numbers:	04-122
Study First Received:	January 7, 2008
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00594633
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Cognitive dysfunction

Study placed in the following topic categories:

Brain Neoplasms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Donepezil
Central Nervous System Diseases
Central Nervous System Neoplasms

Dementia
Brain Diseases
Nervous System Neoplasms
Cognition Disorders
Delirium

Additional relevant MeSH terms:

Nootropic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs
Enzyme Inhibitors
Cholinergic Agents

Pharmacologic Actions
Cholinesterase Inhibitors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009