Treatment Study of Frontotemporal Dementia
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Frontotemporal Lobar Degeneration
Phase: N/A
Status: Completed
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)
Summary
Objectives. The proposed clinical study has two goals: First, to assess the efficacy of a
central nervous system stimulant and an atypical antipsychotic in treating the behavioral
symptoms of FTD and second, to further characterize the biological markers, including
genetic, imaging, and CSF proteins, of FTD in relation to our existing group of Alzheimer's
patients.
Rationale. Frontotemporal dementia (FTD) is increasingly recognized as an important
neuropsychiatric disorder. Symptoms of FTD include disinhibition, impulsivity, apathy,
affective lability, and language dysfunction. The clinical syndrome is associated with
frontal and/or anterior temporal atrophy on imaging and autopsy. Levels of the CSF proteins
tau and (Beta)-amyloid 1-42, shown to have diagnostic utility in patients with Alzheimer's
Disease (AD), have also been found to be abnormal in FTD. FTD is less associated with APOE
genotype than AD, however some familial cases of FTD are associated with specific mutations
in the gene encoding the tau protein. Currently, no treatments have been proven to be
effective for altering the course or clinical symptoms of FTD.
Design. Study subjects will include 50 male and female patients with mild-moderate
frontotemporal dementia recruited from participants in NINDS protocol 02-N-0001. In a
double-blinded crossover 11-week study without a placebo control, patients will be treated
with a stimulant (dextroamphetamine) and an atypical antipsychotic (quetiapine). The
primary outcome measures will be the Neuropsychiatric Inventory and the Clinical Global
Impression of Change. Cerebrospinal fluid, cognitive and genetic measures, brain MRIs, and
side effects scales will also be collected.
Clinical Details
Official title: Treatment Study for Frontotemporal Dementia
Study design: N/A
Detailed description:
Objectives. The goal of the proposed clinical study is to assess the efficacy of a central
nervous system stimulant and an atypical antipsychotic in treating the behavioral symptoms
of FTD.
Rationale. Frontotemporal dementia (FTD) is increasingly recognized as an important
neuropsychiatric disorder. Symptoms of FTD include disinhibition, impulsivity, apathy,
affective lability, and language dysfunction. The clinical syndrome is associated with
frontal and/or anterior temporal atrophy on imaging and autopsy. Currently, no treatments
have been proven to be effective for altering the course or clinical symptoms of FTD.
Design. Study subjects will include 20 male and female patients with mild-moderate
frontotemporal dementia recruited from participants in NINDS protocols 02-N-0001 and
81-N-0010. In a double-blinded crossover 11-week study without a placebo control, patients
will be treated with a stimulant (dextroamphetamine) and an atypical antipsychotic
(quetiapine). The primary outcome measures will be the Neuropsychiatric Inventory and the
Clinical Global Impression of Change. Cognitive measures and side effects scales will also
be collected.
Eligibility
Minimum age: 45 Years.
Maximum age: 95 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
1. FTD as diagnosed by the Lund-Manchester criteria including patients with
diagnoses of Semantic Dementia or Primary Progressive Aphasia.
2. Ages 45 to 95 years old.
3. Mild-to-moderate (CDR 1 to 2) FTD with an assigned durable power of attorney.
EXCLUSION CRITERIA:
1. 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.
2. Severe dementia (CDR 3).
3. Known allergy or serious adverse reaction to quetiapine or dextroamphetamine.
4. Patient is already receiving a stimulant (methylphenidate, dextroamphetamine,
pemoline, or modafinil), or an antipsychotic medication, typical or atypical,
including prochlorperazine and metoclopromide.
5. 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.
6. Patients taking the following medications because of their potential interaction with
quetiapine: Carbamazepine, clozapine, lithium, thioridazine.
7. History of CVA, or at significantly increased risk for CVA (e. g., atrial
fibrillation, recent TIA etc.).
8. Symptomatic cardiovascular disease (i. e., angina, claudication, TIAs, syncope),
uncontrolled hyper or hypotension, or a tic disorder.
9. Any medical contraindication to performing the procedures involved in the study
including blood draws or lumbar puncture.
10. 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.
11. Patients with a previous negative trial of a stimulant.
12. Patients with a history of severe psychosis.
13. Patients with a history of recent substance abuse.
14. Patients with QTc prolongation on a baseline EKG.
15. A score of 2 or less on the Communication Functional Ratings - Swallowing Domain.
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information
Related publications: 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. Satel SL, Nelson JC. Stimulants in the treatment of depression: a critical overview. J Clin Psychiatry. 1989 Jul;50(7):241-9. Review. 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.
Starting date: July 2004
Last updated: June 3, 2009
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