Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

Condition(s) targeted: Frontal Lobe Dementia; Frontotemporal Lobe Dementia; Semantic Dementia

Intervention: memantine (Drug); Placebo pill (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of California, San Francisco

Official(s) and/or principal investigator(s):
Adam L. Boxer, M.D., Ph.D., Principal Investigator, Affiliation: University of California, San Francisco
Bruce Miller, M.D., Principal Investigator, Affiliation: University of California, San Francisco

Overall contact:
Robert Nicholson, B.A., Phone: 415-476-0662, Email: rnicholson@memory.ucsf.edu

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

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Efficacy Study

Primary outcome: Neuropsychiatric Inventory (NPI) 1 total score Clinical Global Impression Change (CGIC)

Secondary outcome:

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

multiple secondary outcome measures

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.

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

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.

Robert Nicholson, B.A., Phone: 415-476-0662, Email: rnicholson@memory.ucsf.edu

University of California, Los Angeles, Los Angeles, California 90095, United States; Recruiting
Jill Shapira, R.N., Ph.D., Phone: 310-794-2550
Mario Mendez, M.D., Principal Investigator

University California, San Francisco, San Francisco, California 94143-1207, United States; Recruiting
Robert Nicholson, BA, Phone: 415-476-0662, Email: rnicholson@memory.ucsf.edu
Mary Koestler, RN,PhD, Phone: 415-476-0661, Email: mkoestler@memory.ucsf.edu
Adam L. Boxer, M.D., Ph.D., Principal Investigator

Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States; Recruiting
Dana Kistler, Phone: 904-953-9680, Email: kistler.dana@mayo.edu
Neill GraffRadford, M.D., Principal Investigator

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Kristine Lipowski, Phone: 312-695-2343, Email: k-lipowski@northwestern.edu
Chuang-Kuo Wu, M.D., Principal Investigator

Johns Hopkins Hospital, Baltimore, Maryland 21205, United States; Recruiting
Sandeepa Sur, MA, Phone: 410-502-3747, Email: ssur3@jhmi.edu
Chiadi Onyike, M.D., Principal Investigator

Mayo Clinic - Rochester, Rochester, Minnesota 55905, United States; Recruiting
Nancy Haukom, Phone: 507-266-8485, Email: Haukom.Nancy@mayo.edu
David Knopman, M.D., Principal Investigator

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7025, United States; Recruiting
Charlene Riedel-Leo, M.Ed., MSW, Phone: 919-966-5039, Email: charlenerl@neurology.unc.edu
Daniel I. Kaufer, M.D., Principal Investigator

University Hospitals of Cleveland / Case Medical Center, Cleveland, Ohio 44120, United States; Recruiting
Leon Hudson, Phone: 216-844-6411, Email: Leon.Hudson@case.edu
Alan Lerner, M.D., Principal Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States; Recruiting
Lauren Massimo, Phone: 215-349-8464, Email: massimol@uphs.upenn.edu
Murray Grossman, M.D., Principal Investigator

UCSF Memory and Aging Center

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Starting date: October 2007
Ending date: June 2010
Last updated: October 7, 2009