Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia
Condition: Frontal Lobe Dementia; Frontotemporal Lobe Dementia; Semantic Dementia
MeSH terms: Dementia; Alzheimer Disease; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
Intervention: memantine; Placebo pill
Intervention description: memantine 10mg BID; Placebo pill BID
Intervention MeSH terms: Memantine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 81.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Randomized; Double-Blind; Placebo-Controlled; memantine; Namenda; Frontotemporal Dementia; Semantic Dementia; FTD; SD; dementia; behavioral decline; cognitive decline

Summary:

      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
    

Eligibility 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.