Effects of Tolcapone on Frontotemporal Dementia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Edward D Huey, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT00604591
First received: January 19, 2008
Last updated: June 14, 2016
Last verified: June 2016
  Purpose

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.

Condition Intervention Phase
Frontotemporal Lobar Degeneration
Drug: Tolcapone
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 28
Study Start Date: July 2011
Estimated Study Completion Date: October 2016
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo then Tolcapone

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.

Drug: Tolcapone
200 mg by mouth three times a day
Other Name: Tasmar
Drug: Placebo
200 mg by mouth three times a day
Other Name: Sugar pill
Experimental: Tolcapone then Placebo

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.

Drug: Tolcapone
200 mg by mouth three times a day
Other Name: Tasmar
Drug: Placebo
200 mg by mouth three times a day
Other Name: Sugar pill

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.
  Eligibility

Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00604591

Locations
United States, New York
Columbia University Medical Center, 622 West 168th Street
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Edward Huey, MD Columbia University
  More Information

Publications:
Responsible Party: Edward D Huey, MD, Assistant Professor of Psychiatry and Neurology (In the Taub Institute), Columbia University
ClinicalTrials.gov Identifier: NCT00604591     History of Changes
Other Study ID Numbers: AAAF4151  5R00NS060766 
Study First Received: January 19, 2008
Last Updated: June 14, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Columbia University:
Dementia Treatment
Frontotemporal Dementia
Dopamine
Frontotemporal Lobar Degeneration

Additional relevant MeSH terms:
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Dopamine
Tolcapone
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 30, 2016