Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)

Dementia Clinical Trial

Official title:

Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00127114
• Other study ID #: 04033101
• Status: Withdrawn
• Phase: Phase 4
• First received: August 3, 2005
• Last updated: August 10, 2017
• Start date: September 2005
• Est. completion date: July 26, 2007

Study information

• Verified date: August 2017
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 26, 2007
• Est. primary completion date: July 26, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

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, cortical-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.

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Pick Disease of the Brain
• Problem Behavior

Intervention

Drug:
• Amantadine

• Placebo

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine, Outpatient General Clinical Research Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Drayton SJ, Davies K, Steinberg M, Leroi I, Rosenblatt A, Lyketsos CG. Amantadine for executive dysfunction syndrome in patients with dementia. Psychosomatics. 2004 May-Jun;45(3):205-9. — View Citation

Imamura T, Takanashi M, Hattori N, Fujimori M, Yamashita H, Ishii K, Yamadori A. Bromocriptine treatment for perseveration in demented patients. Alzheimer Dis Assoc Disord. 1998 Jun;12(2):109-13. — View Citation

Kertesz A, Davidson W, McCabe P, Munoz D. Behavioral quantitation is more sensitive than cognitive testing in frontotemporal dementia. Alzheimer Dis Assoc Disord. 2003 Oct-Dec;17(4):223-9. — View Citation

McDowell S, Whyte J, D'Esposito M. Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain. 1998 Jun;121 ( Pt 6):1155-64. — View Citation

O'Suilleabhain P, Dewey RB Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003 Jul;60(7):996-8. — View Citation

Sjögren M, Minthon L, Passant U, Blennow K, Wallin A. Decreased monoamine metabolites in frontotemporal dementia and Alzheimer's disease. Neurobiol Aging. 1998 Sep-Oct;19(5):379-84. — View Citation

Van Reekum R, Bayley M, Garner S, Burke IM, Fawcett S, Hart A, Thompson W. N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. Brain Inj. 1995 Jan;9(1):49-53. — View Citation

Verhagen Metman L, Morris MJ, Farmer C, Gillespie M, Mosby K, Wuu J, Chase TN. Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002 Sep 10;59(5):694-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frontal Behavioral Inventory, disinhibition subscale		6 weeks
Secondary	Frontal Behavior Inventory, total score		6 weeks
Secondary	Neuropsychiatric Inventory		6 weeks
Secondary	Apathy Evaluation Scale		6 weeks
Secondary	Cognitive measures - Mini Mental State Exam (MMSE), Trails Making Test A&B (Trails A&B), Verbal fluency, and Stroop test		6 weeks
Secondary	Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) measures		6 weeks
Secondary	Zarit Burden Interview		6 weeks