Effects of Tolcapone on Frontotemporal Dementia
Condition: Frontotemporal Lobar Degeneration
MeSH terms: Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Frontotemporal Lobar Degeneration
Study type: Interventional
Phase: Phase 2

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.
    

Detailed 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.
    

Intervention name(s): Tolcapone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 200 mg by mouth three times a day; 200 mg by mouth three times a day
Other intervention name(s): Tasmar; Sugar pill
Intervention MeSH terms: Tolcapone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Dementia Treatment; Frontotemporal Dementia; Dopamine; Frontotemporal Lobar Degeneration