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Completed

NCT Number: NCT00604591

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.

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Key information

Conditions

Frontotemporal Lobar Degeneration Brain Diseases Central Nervous System Diseases Dementia Frontotemporal Dementia Mental Disorders Metabolic Diseases Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies TDP-43 Proteinopathies

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Columbia University Irving Medical Center

New York, 10032, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tolcapone

Drug

200 mg by mouth three times a day

Other names: Tasmar

Placebo

Drug

200 mg by mouth three times a day

Other names: Sugar pill

Primary outcomes

  1. Reaction Time on the N-back Cognitive Test (0-back Condition)

    Time frame: First intervention: Day 8 and Second intervention: Day 21

    In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 0-back condition, the subjects are instructed to press the button with the number on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.

  2. Reaction Time on the N-back Cognitive Test (1-back Condition)

    Time frame: First intervention: Day 8 and Second intervention: Day 21

    In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 1-back condition, the subjects are instructed to report the number presented one number back from the number displayed on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.

Secondary outcomes

  1. Score on Neuropsychiatric Inventory Questionnaire (NPI-Q)

    Time frame: First intervention: Day 8 and Second intervention: Day 21

    The NPI-Q is a retrospective caregiver/informant-based interview that assesses 12 neuropsychiatric symptom domains including delusions, hallucinations, agitation/aggression, depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, night-time behavioral disturbances and appetite/eating disturbances. Each symptom within a domain are rated by the caregiver in terms of severity (1=mild to 3=severe). Total scores are calculated by adding the composite scores to obtain a score ranging from 0 (no symptoms, better outcome) to 36.

  2. Score on the Repeated Battery for the Assessment of Neurological Status (RBANS) for Dementia

    Time frame: First intervention: Day 8 and Second intervention: Day 21

    The RBANS is a brief, individually administered test that captures multiple cognitive domains, including attention, language, visuospatial/constructional abilities, immediate memory, and delayed memory. Index scores range from 0 to 20 (better outcome) for each of the 5 domains tested and the composite scores are added to generated a total index score, which ranges from 0 to 100 (better outcome).

  3. Score on the Clinical Global Impressions (CGI) Scale

    Time frame: First intervention: Day 8 and Second intervention: Day 21

    The CGI is often used in treatment studies as a proxy for global functioning and is a subjective score assigned by the treating physician that incorporates elements of illness severity, patient distress, patient impairment, and functioning. The CGI is given a numerical ranking each visit after the first, with 6=major worsening, 5=mild worsening, 4=no change, 3=mild improvement, and 2=major improvement. Scores range from a 2 (better outcome) to a 6 (worse outcome).

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

Investigation of the Dopamine System in Frontotemporal Dementia

Important dates

Study start
2008
Primary completion
2016
Study completion
2016
First posted
Jan 30, 2008
Registry last updated
Aug 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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