Therapy in Amyotrophic Lateral Sclerosis (TAME)
Condition: Amyotrophic Lateral Sclerosis; Frontal Temporal Dementia
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Memantine; Placebo (for Memantine)
Intervention description: All randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo.; All randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo.
Intervention MeSH terms: Memantine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: ALS; FTD; Tau; pNF-H/C3

Summary:

      The purpose of this study is to determine if memantine at up to 20 mg twice a day when used
      in conjunction with riluzole, can slow down the disease progression of patients with ALS
      including potentially improving their neuropsychiatric changes, as well as determine if serum
      biomarkers can be used both as a diagnostic and a prognostic marker in patients with ALS.

      Funding Source: FDA - Orphan Products Development (OPD)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-85

          2. Male or Female

          3. Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial
             criteria

          4. ALSFRS-R > 25

          5. Must be willing to undergo longitudinal blood draws for biomarker analysis

          6. Availability and willingness to complete the study

          7. Capable of providing informed consent and complying with trial procedures

          8. If patients are taking riluzole and/or Radicava, they must be a on a stable dose for
             at least thirty days prior to the baseline.

        Exclusion Criteria:

          1. Patients with forced vital capacity (FVC) ≤ 60%

          2. History of liver disease

          3. Severe renal failure

          4. History of intolerance to memantine

          5. Onset of weakness for greater than 3 years

          6. Any other co-morbid condition which would make completion of the trial unlikely

          7. If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to
             use birth control.

          8. Taking any investigational medications. If the patient was previously on
             investigational medications, a 30-day washout period is required before the baseline
             visit. Non-trial medications are not cause for exclusion.

          9. Unwillingness to provide consent

        Remote Inclusion Criteria:

          1. Age 18-85

          2. Male or Female

          3. Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial
             criteria

          4. ALSFRS-R > 25

          5. Must be willing to undergo longitudinal blood draws for biomarker analysis. This may
             be foregone during the screening visit

          6. Availability and willingness to complete the study

          7. Capable of providing informed consent and complying with trial procedures

          8. If patients are taking riluzole and/or Radicava, they must be a on a stable dose for
             at least thirty days prior to the baseline

          9. Documentation of not clinically significant liver enzymes within the previous 6 months

        Remote Exclusion Criteria:

          1. Patients with FVC ≤ 60%*

          2. History of liver disease

          3. Severe renal failure

          4. History of intolerance to memantine

          5. Onset of weakness for greater than 3 years

          6. Any other co-morbid condition which would make completion of the trial unlikely

          7. If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to
             use birth control.

          8. Taking any investigational medications. If the patient was previously on
             investigational medications, a 30-day washout period is required before the baseline
             visit. Non-trial medications are not cause for exclusion.

          9. Unwillingness to provide consent

               -  Since FVC cannot be captured during a remote screening visit, and acceptable FVC
                  performed within the previous 90 days is acceptable. If an FVC is not available
                  within the previous 90 days, the subject may be enrolled if the local site PI
                  believes the subject has no significant shortness of breath or respiratory
                  issues.