Overview

This trial is active, not recruiting.

Condition frontotemporal lobar degeneration
Treatments tolcapone, placebo
Phase phase 2
Sponsor Columbia University
Collaborator National Institute of Neurological Disorders and Stroke (NINDS)
Start date July 2011
End date August 2015
Trial size 28 participants
Trial identifier NCT00604591, 5R00NS060766, AAAF4151

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
Participants take placebo during study week 1 and then tolcapone during week 3. On Day 1, 100 mg of tolcapone/placebo will be taken at three specific times: once in the morning, once in the afternoon, once at night. Then, from Days 2-6, 200 mg of tolcapone/placebo will be taken three times a day: once in the morning, once in the afternoon, once at night. On Day 7, 200 mg of tolcapone/placebo will be taken only in the morning and afternoon. On Day 8, 200 mg of tolcapone/placebo will be taken only in the morning. After the last dose on Day 8 is taken, the wash-out period begins and lasts through Day 14.
tolcapone Tasmar
200 mg by mouth three times a day
placebo Sugar pill
200 mg by mouth three times a day
(Experimental)
Participants take tolcapone during study week 1 and then placebo during week 3. On Day 1, 100 mg of tolcapone/placebo will be taken at three specific times: once in the morning, once in the afternoon, once at night. Then, from Days 2-6, 200 mg of tolcapone/placebo will be taken three times a day: once in the morning, once in the afternoon, once at night. On Day 7, 200 mg of tolcapone/placebo will be taken only in the morning and afternoon. On Day 8, 200 mg of tolcapone/placebo will be taken only in the morning. After the last dose on Day 8 is taken, the wash-out period begins and lasts through Day 14.
tolcapone Tasmar
200 mg by mouth three times a day
placebo Sugar pill
200 mg by mouth three times a day

Primary Outcomes

Measure
Reaction time on the most difficult N-back condition that the patients can successfully perform.
time frame: To complete over the next 3 years.

Secondary Outcomes

Measure
A difference in the normalized BOLD signal intensity between subjects on placebo vs. tolcapone.
time frame: To complete over the next 3 years.

Eligibility Criteria

Male or female participants from 40 years up to 85 years old.

Inclusion Criteria: - Diagnosis of frontotemporal dementia (FTD) - Age 40 to 85 - Assigned durable power of attorney - Caregiver willing and able to accept the responsibilities involved in the study - Mattis Dementia Rating Scale-2 (MDRS2) score less than 132 Exclusion Criteria: - The diagnosis of any other type of dementia besides FTD including Alzheimer's disease, Lewy body dementia, vascular dementia, dementia associated with Parkinson's disease, corticobasal syndrome, and progressive supranuclear palsy. - Known allergy or serious adverse reaction to tolcapone - Active liver disease - Current alcohol abuse - Active substance abuse - Elevated liver function tests - Patient is taking tolcapone or any other catechol-O-methyltransferase (COMT) inhibitor, benserazide, alpha-methyldopa, dobutamine, apomorphine, isoproterenol, an monoamine oxidase inhibitor (MAO-I), or clozapine - Symptomatic cardiovascular disease (e.g., angina, transient ischemic attack (TIA) , syncope) - Uncontrolled hyper- or hypotension - Any other contraindication to tolcapone - Any medication that significantly affects the dopamine system, including stimulants and antipsychotic medications - Pregnant women

Additional Information

Official title Investigation of the Dopamine System in Frontotemporal Dementia
Principal investigator Edward Huey, MD
Description FTD is a significant cause of disability and death with an estimated prevalence of 15 cases per 100,000 persons in the 45- to 64-year-old age range. Despite the magnitude of this problem, there is currently a relative lack of understanding of the causes of, and treatments for, FTD, possibly because criteria for its diagnosis have only recently been developed. As an outcome of the proposed investigations, the investigators expect to determine the effects of cortical dopamine augmentation in FTD, evaluate the effect of dopamine augmentation on processing efficiency with fMRI, and explore the effects of a genetic polymorphism on symptom presentation and disease course. The research proposed in this protocol is significant because it could provide a new class of treatments for FTD, identify the fMRI findings associated with symptom improvement, and determine the contribution of a genetic polymorphism to symptom presentation and disease course.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Columbia University.