The purpose of this clinical trial is to test whether or not the medication amantadine is effective in reducing behavioral disturbances in patients with frontotemporal dementia.

Condition	Intervention	Phase
Dementia	Drug: amantadine	Phase IV

Further Study Details: 

Primary Outcomes: Frontal Behavioral Inventory, disinhibition subscale
Secondary Outcomes: Frontal Behavior Inventory, total score; Neuropsychiatric Inventory; Apathy Evaluation Scale; Cognitive measures - Mini Mental State Exam (MMSE), Trails Making Test A&B (Trails A&B), Verbal fluency, and Stroop test; Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) measures; Zarit Burden Interview
Expected Total Enrollment:  52

Behavioral disturbances are a major cause of morbidity in frontotemporal dementia (FTD), yet little is known about the effectiveness of medications to treat these disturbances. Preliminary data suggests that the dopaminergic agent amantadine may reduce these disturbances. This 6-week, prospective, randomized, placebo-controlled trial will compare amantadine to placebo to assess its effectiveness in reducing behavioral symptoms.

Ages Eligible for Study:  40 Years   -   90 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Frontotemporal dementia meeting diagnostic criteria of the Report of the Work Group on Frontotemporal Dementia and Pick’s Disease (McKhann et al, 2001). Diagnosis will be established by clinical interview by a geriatric psychiatrist or neuropsychiatrist, experienced with the diagnosis of FTD. Patients with the language presentation of FTD will be enrolled if their behavioral disturbance meets the inclusion criteria. Use of these diagnostic criteria would allow for enrollment of patients who in a clinical setting carry the diagnosis of: semantic dementia, primary progressive aphasia, cortic-basal degeneration, progressive supranuclear palsy, (amyotrophic lateral sclerosis (ALS) with dementia, and Pick''''s disease, as all of these diagnoses are now classified under the rubric of FTD.
• Frontal Behavioral Inventory (FBI) disinhibition subscale score of >16 (Kertesz et al,1997; Kertesz et al 2000). Explanation of this subscale is found under outcome measures.
• Men, women and minority groups will be included, ages 40-90 years old.
• Judged by the attending psychiatrist to be in sufficiently good health so as to be treated using the study protocol in usual outpatient care circumstances.
• Patient, caregivers and or legal representatives provide informed consent for participation in the study, using standard Johns Hopkins Division of Geriatric Psychiatry and Neuropsychiatry procedures.
• Caregiver is available who spends at least 10 hours per week with the patient and is able and willing to accompany the patient in the course of the study and to provide collateral information.

Exclusion Criteria:

• Presence of a brain disease that might otherwise fully explain the presence of dementia or behavior disturbance, such as stroke, Parkinson’s disease, traumatic brain injury, multiple sclerosis, and the like.
• Treatment with amantadine is contraindicated in the opinion of the study attending psychiatrist. Examples of this would be patients with advanced heart, liver or kidney disease or a seizure disorder. Creatinine clearance >50mL/min will be required, calculated using the Cockcroft-Gault equation.
• Failure of treatment with amantadine for behavior disturbance of FTD in the past.
• Treatment with a medication that would prohibit the safe concurrent use of amantadine.
• Ongoing regular alcohol use and an unwillingness to stop drinking alcohol during the study period.
• Pregnancy or lactation.

Please refer to this study by ClinicalTrials.gov identifier  NCT00127114

Melanie Dieter, M.A.      410-955-8702    mdieter1@jhmi.edu
David M Blass, M.D.      410-955-6736    dmblass@jhmi.edu

Maryland
      Johns Hopkins University School of Medicine, Outpatient General Clinical Research Center, Baltimore,  Maryland,  21287,  United States

Study chairs or principal investigators

David M Blass, M.D.,  Principal Investigator,  Johns Hopkins University   

Study ID Numbers:  04033101
Last Updated:  August 22, 2005
Record first received:  August 3, 2005
ClinicalTrials.gov Identifier:  NCT00127114
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-08-23