Adjunctive Donepezil Therapy and Genetic Risk Factors of Cognitive Dysfunction in Brain Tumor Survivors

08:21 EST 28th November 2014 | BioPortfolio

Summary

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.

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Brain Tumor

Intervention

donepezil and questionaires

Location

Memorial Sloan Kettering Cancer Center
New York
New York
United States
10065

Status

Active, not recruiting

Source

Memorial Sloan-Kettering Cancer Center

Results (where available)

View Results

Links

Clinical Trials [708 Associated Clinical Trials listed on BioPortfolio]

Donepezil or EGb761 in Improving Neurocognitive Function in Patients Who Have Previously Undergone Radiation Therapy for Primary Brain Tumor or Brain Metastases

RATIONALE: Donepezil and EGb761 may be effective in improving neurocognitive function (such as thinking, attention, concentration, and memory) and may improve quality of life in patients w...

Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

RATIONALE: Donepezil may decrease the side effects caused by radiation therapy to the brain. PURPOSE: This clinical trial is studying how well donepezil works in treating young patients w...

Donepezil and Brain Activity Patterns in Those at Risk For Alzheimer's Disease

The purpose of the study is to examine patterns of brain activity in people who are at risk for memory problems (e.g., Alzheimer's disease or dementia)before and after the medication donep...

Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients

This study investigate the relationship between regional brain volume measured by MRI and donepezil treatment response in patients with Alzheimer's Disease.

Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease

The study hypothesizes that donepezil will have a positive impact on brain blood flow deficits in subjects with memory deficits and/or mild dementia and that improvements in brain blood fl...

PubMed Articles [12629 Associated PubMed Articles listed on BioPortfolio]

The involvement of sigma1 receptors in donepezil induced rescue of hippocampal LTP impaired by beta-amyloid peptide.

Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease (AD). Additional therapeutically relevant target for donepezil is sigma1 receptor (Sig1-R). Beta-amyl...

Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET.

Sigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Al...

Donepezil-Associated Mania in 2 Patients who Were Using Donepezil Without a Prescription.

Pediatric Brain Tumor Cell Lines.

Pediatric brain tumors as a group, including medulloblastomas, gliomas and atypical teratoid rhabdoid tumors (ATRT) are the most common solid tumors in children and the leading cause of death from chi...

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

A large interindividual variability in plasma levels has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic f...

Medical and Biotech [MESH] Definitions

Tissue NECROSIS in any area of the brain, including the CEREBRAL HEMISPHERES, the CEREBELLUM, and the BRAIN STEM. Brain infarction is the result of a cascade of events initiated by inadequate blood flow through the brain that is followed by HYPOXIA and HYPOGLYCEMIA in brain tissue. Damage may be temporary, permanent, selective or pan-necrosis.

Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.

Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.

Multi-channel hearing devices typically used for patients who have tumors on the COCHLEAR NERVE and are unable to benefit from COCHLEAR IMPLANTS after tumor surgery that severs the cochlear nerve. The device electrically stimulates the nerves of cochlea nucleus in the BRAIN STEM rather than the inner ear as in cochlear implants.

Bleeding within the brain as a result of penetrating and nonpenetrating CRANIOCEREBRAL TRAUMA. Traumatically induced hemorrhages may occur in any area of the brain, including the CEREBRUM; BRAIN STEM (see BRAIN STEM HEMORRHAGE, TRAUMATIC); and CEREBELLUM.

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