Protocol Number: 08-N-0045

Title:

Investigation of the Dopamine System in Frontotemporal Dementia

Number:

08-N-0045

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 and who have participated in NINDS protocols 02-N-0001 (Testing a model of the representational knowledge stored in the human prefrontal cortex) and 81-N-0010 (Regional cerebral utilization of glucose in patients with a diagnosis of frontal lobe dementia, atypical parkinsonian disorder, and other basal ganglia disorders) may be eligible for this study.

Participants are admitted to the NIH Clinical Center 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.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Dementia Treatment

Frontotemporal Dementia

Dopamine

Recruitment Keyword(s):

Frontotemporal Dementia

Condition(s):

Frontotemporal Lobar Degeneration

Investigational Drug(s):

None

Investigational Device(s):

None

Interventions:

Drug: Tolcapone

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Adler CH, Singer C, O'Brien C, Hauser RA, Lew MF, Marek KL, Dorflinger E, Pedder S, Deptula D, Yoo K. Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa carbidopa. Tolcapone Fluctuator Study Group III. Arch Neurol. 1998 Aug;55(8):1089-95.

Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, Alce G, Iudicello JE, Akbar N, Egan MF, Goldberg TE, Weinberger DR. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 2007 May;32(5):1011-20. Epub 2006 Oct 25.

Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006 Aug 24;442(7105):916-9. Epub 2006 Jul 16.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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