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Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia
This study is currently recruiting participants.
Verified by University of California, San Francisco, August 2007
Sponsors and Collaborators: University of California, San Francisco
Forest Laboratories
Information provided by: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00545974
  Purpose

The primary objective of the study is to determine whether memantine is effective in slowing the rate of behavioral decline in frontotemporal dementia.

The secondary objective of the study is to assess the safety and tolerability of long-term treatment with memantine in patients with frontotemporal dementia (FTD) or semantic dementia (SD). To determine whether memantine is effective in slowing the rate of cognitive decline in frontotemporal dementia. To evaluate whether memantine delays or decreases the emergence of parkinsonism in frontotemporal dementia.

The tertiary objective of the study is to determine whether treatment with memantine affects changes in weight


Condition Intervention Phase
Frontal Lobe Dementia
Frontotemporal Lobe Dementia
Semantic Dementia
Drug: memantine
Drug: Placebo pill
Phase IV

MedlinePlus related topics: Dementia
Drug Information available for: Memantine Memantine hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Efficacy Study
Official Title: A Prospective, Randomized, Multi-Center, Double-Blind, 26 Week, Placebo-Controlled Trial of Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Neuropsychiatric Inventory (NPI) 1 total score Clinical Global Impression Change (CGIC) [ Time Frame: Visit 2/Week 0; Visit 3/Week6; Visit 4/Week 12; Visit 5/Week 26 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CDR-FTD, MMSE, FAQ, TFLS, EXIT25, UCSF FTD-Neuropsychological Test Battery: CVLT, Verbal fluency, Modified BNT, Backward Digit Span, Digit Symbol Test, Modified Trails B, Modified Unified Parkinson's Disease Rating Scale, antipsychotic therapy [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • multiple secondary outcome measures [ Time Frame: Visit 1/Screening; Visit 2/Week 0; Visit 3/Week 3; Visit 4/Week 6; Visit 5/Week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: October 2007
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Memantine 10mg BID
Drug: memantine
memantine 10mg BID
2: Placebo Comparator
Placebo condition
Drug: Placebo pill
Placebo pill BID

Detailed Description:

This is a multicenter, randomized, double-blind, placebo-controlled trial of memantine 10 mg twice daily versus placebo, at a ratio of 1:1, to receive active drug or placebo. Screening and enrollment is planned to last approximately one year. A Data and Safety Monitoring Board, consisting of a clinical pharmacist and 3 neurologists will review all AE reports approximately every 3 months after study initiation. The DSMB will notify the principal investigator, the study sponsor and the CHR if significant concerns are raised by their review of the AE data. An interim analysis of efficacy data will be conducted after 50% of the targeted enrollment population has completed 26 weeks of drug treatment.

Including screening and off-drug follow up, each subject will participate in the study for approximately 34 weeks.

The entire study is anticipated to last 86 weeks if enrollment is completed within one year of study initiation.

The targeted enrollment is 140.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A subject must meet ALL of the following criteria to be considered for enrollment in this study:

  1. Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations.
  2. Must meet criteria Neary et al. criteria for frontotemporal dementia (FTD) or semantic dementia (SD)
  3. Age: 40-80
  4. CT or MRI of brain within 12 months consistent with a diagnosis of FTD or SD.
  5. MMSE ≥ 15 at screening visit.
  6. Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
  7. Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak English fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
  8. In the opinion of the investigator, the patient and the caregiver will be compliant with the protocol and have a high probability of completing the study.

Exclusion Criteria:

Any one of the following will exclude a subject from being enrolled into the study:

  1. Insufficient fluency in English to complete neuropsychological and functional assessments.
  2. Concurrent Motor Neuron Disease judged by investigator to have bulbar or upper extremity impairments at baseline that would interfere with neuropsychological assessment, or that are expected to lead to such impairments within one month.
  3. Exclusion criteria as listed in Neary criteria. Diagnosis of progressive nonfluent aphasia by Neary criteria.
  4. Use of memantine within 4 weeks prior to randomization.
  5. Evidence of other neurological or psychiatric disorders which preclude diagnosis of FTD (including, but not limited to, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, or head injury with loss of consciousness) within the past year.
  6. Concurrent treatment with acetylcholinesterase inhibitors, antipsychotic agents, mood stabilizers (valproate or lithium) or benzodiazepines (other than temazepam or zolpidem), or use of any of these agents within 4 weeks prior to randomization. Atypical antipsychotic agents may be started after the baseline visit if felt to be medically necessary by the investigator and will be recorded as a secondary outcome measure.
  7. History of alcohol or substance abuse within 1 year prior to screening, if deemed clinically significant by investigator.
  8. Any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
  9. Clinically significant lab abnormalities at screening, including Creatinine ≥ 1.7, B12 below laboratory normal reference range or TSH above site's laboratory normal reference range. Subjects with abnormal B12 or TSH levels at screening may be included per investigator's discretion.

9. CT or MRI evidence of any of the following: hydrocephalus, stroke, space-occupying lesion, cerebral infection or any clinically significant CNS disease other than FTD.

10.Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.

11. Abnormal ECG at screening judged to be clinically significant by the investigator.

12. Use of investigational drugs or participation in investigational drug study within 60 days of screening.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00545974

Contacts
Contact: Kelly Blum, BS 415-476-0662 kblum@memory.ucsf.edu
Contact: Mary Koestler, RN, Ph.D. 415-476-0661 mkoestler@memory.ucsf.edu

Locations
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Jill Shapira, R.N., Ph.D.     310-794-2550        
Principal Investigator: Mario Mendez, M.D.            
University California, San Francisco Recruiting
San Francisco, California, United States, 94143-1207
Contact: Kelly Blum, BS     415-476-0662     kblum@memory.ucsf.edu    
Contact: Mary Koestler, RN,PhD     415-476-0661     mkoestler@memory.ucsf.edu    
Principal Investigator: Adam L. Boxer, M.D., Ph.D.            
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Dana Kistler     904-953-9680     kistler.dana@mayo.edu    
Principal Investigator: Neill GraffRadford, M.D.            
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Kristine Lipowski     312-695-2343     k-lipowski@northwestern.edu    
Principal Investigator: Chuang-Kuo Wu, M.D.            
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Julie Dickson     317-278-4333     judickso@iupui.edu    
Principal Investigator: Ann Marie Hake, M.D.            
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21205
Contact: Sandeepa Sur, MA     410-502-3747     ssur3@jhmi.edu    
Principal Investigator: Chiadi Onyike, M.D.            
United States, Minnesota
Mayo Clinic - Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Nancy Haukom     507-266-8485     Haukom.Nancy@mayo.edu    
Principal Investigator: David Knopman, M.D.            
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lynda Mules     212-305-2077     lm2538@columbia.edu    
Principal Investigator: Karen L. Bell, M.D.            
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7025
Contact: Charlene Riedel-Leo, M.Ed., MSW     919-966-5039     charlenerl@neurology.unc.edu    
Principal Investigator: Daniel I. Kaufer, M.D.            
United States, Ohio
University Hospitals of Cleveland / Case Medical Center Recruiting
Cleveland, Ohio, United States, 44120
Contact: Leon Hudson     216-844-6411     Leon.Hudson@case.edu    
Principal Investigator: Alan Lerner, M.D.            
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Lauren Massimo     215-349-8464     massimol@uphs.upenn.edu    
Principal Investigator: Murray Grossman, M.D.            
Sponsors and Collaborators
University of California, San Francisco
Forest Laboratories
Investigators
Principal Investigator: Adam L. Boxer, M.D., Ph.D. University of California, San Francisco
Principal Investigator: Bruce Miller, M.D. University of California, San Francisco
  More Information

UCSF Memory and Aging Center  This link exits the ClinicalTrials.gov site

Publications:
Amadoro G, Ciotti MT, Costanzi M, Cestari V, Calissano P, Canu N. NMDA receptor mediates tau-induced neurotoxicity by calpain and ERK/MAPK activation. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2892-7. Epub 2006 Feb 13.
Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19 Suppl 1:S3-6. Review.
Boxer AL, Trojanowski JQ, Lee VY-M, Miller BL (2005) Frontotemporal Lobar Degeneration. In: Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics (Beal MF, Lang AE, Ludolph AC, eds), pp 481 - 493. Cambridge, UK: Cambridge University Press.
Cullum CM, Saine K, Chan LD, Martin-Cook K, Gray KF, Weiner MF. Performance-Based instrument to assess functional capacity in dementia: The Texas Functional Living Scale. Neuropsychiatry Neuropsychol Behav Neurol. 2001 Apr-Jun;14(2):103-8.
Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. Review.
Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. No abstract available.
Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, Chatterjee A, Hurtig HI, Karlawish JH, Rosen HJ, Van Deerlin V, Lee VM, Miller BL, Trojanowski JQ, Grossman M. Frontotemporal dementia: clinicopathological correlations. Ann Neurol. 2006 Jun;59(6):952-62.
Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006 Jan 10;66(1):17-22. Review.
Josephs KA, Petersen RC, Knopman DS, Boeve BF, Whitwell JL, Duffy JR, Parisi JE, Dickson DW. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology. 2006 Jan 10;66(1):41-8.
Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, Hauser MF, Witte RJ, Boeve BF, Knopman DS, Dickson DW, Jack CR Jr, Petersen RC. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain. 2006 Jun;129(Pt 6):1385-98. Epub 2006 Apr 13.
Kertesz A, Davidson W, Fox H. Frontal behavioral inventory: diagnostic criteria for frontal lobe dementia. Can J Neurol Sci. 1997 Feb;24(1):29-36.
Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain. 2005 Sep;128(Pt 9):1996-2005. Epub 2005 Jul 20.
Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006 Feb;5(2):160-70. Review.
Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994 Mar 3;330(9):613-22. Review. No abstract available.
Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry. 2007 Jan;15(1):84-7.
Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging. 2004;21(14):931-7.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412-4. No abstract available.
Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546-54. Review.
Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002 Jul;33(7):1834-9.
Pijnenburg YA, Sampson EL, Harvey RJ, Fox NC, Rossor MN. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry. 2003 Jan;18(1):67-72.
Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ; Memantine Study Group. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41.
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Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):317-24.
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Responsible Party: University of California, San Francisco ( Adam Boxer, M.D., Ph.D. - Assistant Professor of Neurology )
Study ID Numbers: NAM-53:memantineplacebo
Study First Received: October 16, 2007
Last Updated: January 12, 2009
ClinicalTrials.gov Identifier: NCT00545974  
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Frontotemporal Dementia
Semantic Dementia
dementia
Dementia
Randomized
Double-Blind
Placebo-Controlled
memantine
Namenda
FTD
ftd
SD
sd
behavioral decline
cognitive decline

Study placed in the following topic categories:
Excitatory Amino Acids
Pick Disease of the Brain
Speech Disorders
Frontotemporal dementia
Aphasia
Central Nervous System Diseases
Language Disorders
Brain Diseases
Aphasia, Primary Progressive
Cognition Disorders
Signs and Symptoms
Dopamine
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Memantine
Neurologic Manifestations
Lobar atrophy of brain
Primary progressive aphasia
Dementia
Neurobehavioral Manifestations
Pick disease of the brain
Communication Disorders
Delirium

Additional relevant MeSH terms:
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases
Antiparkinson Agents
Excitatory Amino Acid Agents
Dopamine Agents
Central Nervous System Agents
Pharmacologic Actions
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on January 16, 2009