Protocol Number: 04-M-0247

Title:

Treatment Study for Frontotemporal Dementia

Number:

04-M-0247

Summary:

This study will evaluate two medications-dextroamphetamine (Dexedrine) and risperidone (Risperdal)-for improving symptoms in patients with frontotemporal dementia (FTD), a disease category that includes primary progressive aphasia and semantic dementia. Dextroamphetamine is a stimulant that has been used for many years to treat depression and apathy. Risperidone is used to treat agitation in patients with dementia.

Patients between 45 and 95 years of age who are diagnosed with mild to moderate FTD may be eligible for this 11-week study. Candidates are recruited from among patients enrolled in NIH study 02-N-0001 and are screened with a physical examination, electrocardiogram (ECG), and blood and urine tests.

Participants are assigned to one of two treatment groups: group 1 takes risperidone for the first half of the study and dextroamphetamine for the second half; group 2 takes dextroamphetamine first and then risperidone. Both medications are taken by mouth, and both are started at a low dose, with gradual increases over 6 days until the target dose is reached. Patients are hospitalized during the first 6 days of treatment and then discharged to continue the drug at home at the target dose for another 3 weeks. At the end of 3 weeks, they return to NIH to start treatment with the second medicine for 6 days and then again return home for 3 weeks. At the end of both treatments, patients return to NIH to discuss their research treatments and future treatment options.

In addition to drug therapy, patients undergo the following tests and procedures to monitor the effects of treatment and to elucidate differences between FTD and other forms of dementia that may be useful in developing new therapies:

- Lumbar puncture (spinal tap): This procedure allows examination of the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. Researchers have found differences in the make-up of CSF in conditions affecting brain function. For the lumbar puncture, a local anesthetic is given at the site of the puncture and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle.

- Blood tests: Blood is tested for possible illnesses that could affect health and memory, for the HIV virus, and for genetic factors that may influence the development and progression of FTD.

- Cognitive testing: Patients take paper and pencil and computer-administered tests to assess their current level of memory and thought processing.

- Other tests: Patients are observed for performance of their activities of daily living and are interviewed about their symptoms.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

-FTD as diagnosed by the Lund-Manchester criteria including patients with diagnoses of Semantic Dementia or Primary Progressive Aphasia.

-Ages 45 to 95 years old

-Mild-to-moderate (CDR(65) 1 to 2) FTD with an assigned durable power of attorney.

EXCLUSION CRITERIA:

-Diagnosis of any form of dementia besides FTD, including AD, Lewy body dementia, vascular dementia, dementia associated with Parkinson's disease, Corticobasal Degeneration and Progressive Supranuclear Palsy.

-Severe dementia (CDR 3).

-Known allergy or serious adverse reaction to quetiapine or dextroamphetamine

-Patient is already receiving a stimulant (methylphenidate, dextroamphetamine, pemoline, or modafinil), or an antipsychotic medication, typical or atypical, including prochlorperazine and metoclopromide.

-Patients taking any of the following medications because of their potential interaction with dextroamphetamine: MAO use currently or within 14 days prior to start of study, Furazolidone, Guanethidine, norepinephrine, sibutramine, tricyclic antidepressants, carbonic anhydrase inhibitors.

-Patients taking the following medications because of their potential interaction with quetiapine: Carbamazepine, clozapine, lithium, thioridazine.

-History of CVA, or at significantly increased risk for CVA (e.g., atrial fibrillation, recent TIA etc.).

-Symptomatic cardiovascular disease (i.e., angina, claudication, TIAs, syncope), uncontrolled hyper or hypotension, or a tic disorder.

-Any medical contraindication to performing the procedures involved in the study including blood draws or lumbar puncture.

-We will require a woman of child-bearing age to have a pregnancy test prior to starting the study medications and to use contraception during the course of the study.

-Patients with a previous negative trial of a stimulant.

-Patients with a history of severe psychosis.

-Patients with a history of recent substance abuse.

-Patients with QTc prolongation on a baseline EKG.

Special Instructions: Currently Not Provided

Keywords:

Frontotemporal Dementia

Alzheimer's Disease

Atypical Antipsychotic

Stimulant

Apathy

Disinhibition

Antipsychotic

Biomarkers

Recruitment Keywords:

Dementia

Frontotemporal Dementia

FTD

Conditions:

Frontotemporal Lobar Degeneration

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Woods SW, Tesar GE, Murray GB, Cassem NH. Psychostimulant treatment of depressive disorders secondary to medical illness. J Clin Psychiatry. 1986 Jan;47(1):12-5. PMID: 3941052

Satel SL, Nelson JC. Stimulants in the treatment of depression: a critical overview. J Clin Psychiatry. 1989 Jul;50(7):241-9. Review. PMID: 2567730

Galynker I, Ieronimo C, Miner C, Rosenblum J, Vilkas N, Rosenthal R. Methylphenidate treatment of negative symptoms in patients with dementia. J Neuropsychiatry Clin Neurosci. 1997 Spring;9(2):231-9. Review. PMID: 9144102

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