Effects of Tolcapone on Frontotemporal Dementia
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 may be eligible for this study.
Participants will be seen as outpatients at the Columbia University Medical Center approximately one a week 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:
- Neurological tests to evaluate attention, problem-solving and memory. These tests are repeated several times during the course of the study.
- Test to look for a gene that affects the amount of dopamine in the brain, using blood samples collected in a previous study.
- Blood draws four times during the study.
- Functional MRI (fMRI) to learn about changes in brain regions that are involved in performing tasks. For fMRI, the patient lies on a table that can slide in and out of the scanner, a narrow metal cylinder surrounded by a magnetic field. The procedure takes about 60 minutes and is performed four times over the course of the . FMRI involves taking pictures of the brain during MRI while the subject performs a task so that changes in the brain that occur during these tasks can be studied.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Investigation of the Dopamine System in Frontotemporal Dementia|
- Reaction time on the most difficult N-back condition that the patients can successfully perform. [ Time Frame: To complete over the next 3 years. ] [ Designated as safety issue: No ]
- A difference in the normalized BOLD signal intensity between subjects on placebo vs. tolcapone. [ Time Frame: To complete over the next 3 years. ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
- 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 describe animal functions and social attributes and perform a working memory task.
- 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 total of approximately 100 patients) 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00604591
|Contact: Edward D Huey, MD||(212) firstname.lastname@example.org|
|United States, New York|
|Columbia University Medical Center, 622 West 168th Street||Recruiting|
|New York, New York, United States, 10032|
|Contact: Edward D Huey, MD 212-305-1134 email@example.com|
|Principal Investigator:||Edward Huey, MD||Columbia University|