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

Primary Purpose

Dementia

Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Amantadine
Placebo
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dementia focused on measuring Behavioral disturbance, Frontotemporal dementia, Dementia, Amantadine, Behavioral disturbance due to frontotemporal dementia

Eligibility Criteria

40 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Johns Hopkins University School of Medicine, Outpatient General Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Amantadine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Frontal Behavioral Inventory, disinhibition subscale

Secondary Outcome Measures

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

Full Information

First Posted
August 3, 2005
Last Updated
August 10, 2017
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT00127114
Brief Title
Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)
Official Title
Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No funding and exclusion criteria were to stringent.
Study Start Date
September 2005 (Actual)
Primary Completion Date
July 26, 2007 (Actual)
Study Completion Date
July 26, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University

4. Oversight

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementia
Keywords
Behavioral disturbance, Frontotemporal dementia, Dementia, Amantadine, Behavioral disturbance due to frontotemporal dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amantadine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Amantadine
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Frontal Behavioral Inventory, disinhibition subscale
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Frontal Behavior Inventory, total score
Time Frame
6 weeks
Title
Neuropsychiatric Inventory
Time Frame
6 weeks
Title
Apathy Evaluation Scale
Time Frame
6 weeks
Title
Cognitive measures - Mini Mental State Exam (MMSE), Trails Making Test A&B (Trails A&B), Verbal fluency, and Stroop test
Time Frame
6 weeks
Title
Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) measures
Time Frame
6 weeks
Title
Zarit Burden Interview
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility 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, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David M Blass, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University School of Medicine, Outpatient General Clinical Research Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15123844
Citation
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. doi: 10.1176/appi.psy.45.3.205.
Results Reference
background
PubMed Identifier
12873857
Citation
O'Suilleabhain P, Dewey RB Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003 Jul;60(7):996-8. doi: 10.1001/archneur.60.7.996.
Results Reference
background
PubMed Identifier
12221159
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. doi: 10.1212/wnl.59.5.694.
Results Reference
background
PubMed Identifier
7874096
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. doi: 10.3109/02699059509004571.
Results Reference
background
PubMed Identifier
9651140
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. doi: 10.1097/00002093-199806000-00009.
Results Reference
background
PubMed Identifier
14657786
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. doi: 10.1097/00002093-200310000-00005.
Results Reference
background
PubMed Identifier
9648550
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. doi: 10.1093/brain/121.6.1155.
Results Reference
background
PubMed Identifier
9880039
Citation
Sjogren 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. doi: 10.1016/s0197-4580(98)00086-4.
Results Reference
background

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

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