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Sponsored by: |
National Institute of Neurological Disorders and Stroke (NINDS) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00604591 |
This study will test the effects of a medication called tolcapone on cognitive, behavioral, and language problems seen in patients with frontotemporal dementia (FTD). Tolcapone increases the amount of dopamine, a brain chemical that may be lowered in FTD. The study will see if tolcapone can improve thinking, behavior, and language in people with FTD and will look at the effects of the drug on brain activity.
Patients with FTD who are between 40 and 85 years of age and who have participated in NINDS protocols 02-N-0001 (Testing a model of the representational knowledge stored in the human prefrontal cortex) and 81-N-0010 (Regional cerebral utilization of glucose in patients with a diagnosis of frontal lobe dementia, atypical parkinsonian disorder, and other basal ganglia disorders) may be eligible for this study.
Participants are admitted to the NIH Clinical Center for 4 weeks. They take tolcapone or a placebo (a look-alike pill with no active ingredient) during study week 1. During study week 3, those who took placebo during week 1 now take tolcapone for 1 week and those who took tolcapone now take placebo. In addition, patients undergo the following tests and procedures:
Condition | Intervention | Phase |
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Frontotemporal Lobar Degeneration |
Drug: Tolcapone |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Efficacy Study |
Official Title: | Investigation of the Dopamine System in Frontotemporal Dementia |
Estimated Enrollment: | 30 |
Study Start Date: | January 2008 |
Objective: 1) To test the clinical and cognitive effects on frontotemporal dementia (FTD) patients of a medication that increases the amount of the neurotransmitter dopamine in the brain. In autopsy, cerebrospinal fluid, and imaging studies, patients with frontotemporal dementia demonstrate deficiencies in the dopamine neurotransmitter system. This medication acts by inhibiting an enzyme, catechol O-methyl-transferase (COMT), that degrades dopamine. The proposed project will also use fMRI to determine the effects of COMT inhibition on prefrontal cortex and temporal lobe efficiency at rest and while the patients read words that decribe animal functions and social attributes and perform a working memory task. 2) Determine the effect of COMT genotype on symptom presentation and disease course in FTD patients. The COMT gene has a common polymorphism that affects its function.
Study population: 30 patients with FTD will participate in the medication trial. These patients will be included with a larger group of FTD patients (for a totoal of approximately 100 patients) who have participated in NINDS protocols 81-N-0010 and 02-N-0001 for the analyses of the effect of COMT genotype on symptom presentation and progression.
Research Design: A 24-day double-blind, placebo-controlled crossover trial and an analysis of COMT genotype on symptom presentation and progression.
Outcome measures: 1) A comparison of measures of behavioral and cognitive symptoms, and fMRI blood oxygenation level-dependent (BOLD) activation in the prefrontal cortex and temporal lobe, when the patients are taking a COMT inhibitor versus when they are taking a placebo. 2) A comparison between COMT genotypes of the ratio of verbal fluency to overall score on the RBANS cognitive battery and loss in points on the Mattis DRS-2 divided by symptom duration.
Ages Eligible for Study: | 40 Years to 85 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
EXCLUSION CRITERIA:
Responsible Party: | National Institutes of Health ( Edward D. Huey, M.D./National Institute of Neurological Disorders and Stroke ) |
Study ID Numbers: | 080045, 08-N-0045 |
Study First Received: | January 19, 2008 |
Last Updated: | October 24, 2008 |
ClinicalTrials.gov Identifier: | NCT00604591 |
Health Authority: | United States: Federal Government |
Dementia Treatment Frontotemporal Dementia Dopamine Frontotemporal Dementia |
Pick Disease of the Brain Speech Disorders Frontotemporal dementia Aphasia Tolcapone Central Nervous System Diseases Language Disorders Brain Diseases Aphasia, Primary Progressive Cognition Disorders Signs and Symptoms |
Dopamine Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Neurologic Manifestations Lobar atrophy of brain Primary progressive aphasia Dementia Neurobehavioral Manifestations Pick disease of the brain Communication Disorders Delirium |
Molecular Mechanisms of Pharmacological Action Anti-Dyskinesia Agents Therapeutic Uses Nervous System Diseases |
Antiparkinson Agents Enzyme Inhibitors Central Nervous System Agents Pharmacologic Actions |