A Pilot Clinical Trial Of Memantine for Essential Tremor
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Clinical Trial of Memantine for Essential Tremor|
- The degree of tremor at the end of the dose adjustment phase compared to baseline [ Time Frame: Six months ] [ Designated as safety issue: No ]
- Quality of Life. [ Time Frame: Six months ] [ Designated as safety issue: No ]
- Degree of tremor at the end of the extension phase compared to the beginning of the extension phase. [ Time Frame: Six months ] [ Designated as safety issue: No ]
|Study Start Date:||February 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Background: Essential tremor (ET) is the most common movement disorder but has relatively few effective and tolerated therapies. Tremor in ET is believed to be generated by a central oscillator, the inferior olivary nucleus. Membrane potentials in neurons of this nucleus oscillate at tremor frequency. Evidence indicates that the ability of this nucleus to produce tremor is medicated by glutamate acting on the NMDA receptor. As NMDA receptor antagonists suppress tremor, it is suggested that memantine, a low affinity NMDA antagonist, will be effective for essential tremor.
Objective: To assess the efficacy, safety and stability of response to memantine in a pilot single-site feasibility rising-dose trial in the treatment of essential tremor.
Method: Subjects with bilateral upper extremity essential tremor, on no essential tremor therapy, or on a stable-dose therapy, will have laboratory tests and EKG tests at a screening visit. Eligible subjects will have baseline tremor assessments with standardized rating scales. The tremor will be videotaped. In the first titration step, all subjects will take memantine at the dose of 5 mg/day for 2 weeks, then 5 mg twice a day for another 2 weeks, and tremor again assessed. In the second titration step the dose will similarly be raised to 20 mg/day, taken as 10 mg twice a day, and tremor assessed 4 weeks after the last tremor assessment. In the third titration step, the dose will be raised to 30 mg/day, taken as 15 mg twice a day, and tremor assessed at the conclusion of the third titration step. In the fourth titration step, the dose will be raised to 40 mg/day, taken as 20 mg twice a day, and tremor assessed at the conclusion of the fourth titration step. The dose will be adjusted downwards if titration is not tolerated. Subjects who achieve a clinically meaningful tremor reduction will enter a 12-week extension study assessing the stability of the tremor response.
Data analysis: Subjects will be recruited according to a two-part Gehan design. A "responder" is defined as a 30% reduction in the tremor score. To assess whether memantine has a potential responder rate of 30 percent, 9 subjects will be recruited in the first phase. If at least one subject is a responder, another 16 subjects will be recruited to estimate the actual responder rate with a standard error of 10%.
Conclusions: If memantine is effective in suppressing tremor, it would be welcomed by patients and the movement disorders community as a well-tolerated new treatment for essential tremor.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00439699
|United States, California|
|VA Greater Los Angeles|
|Los Angeles, California, United States, 90073|
|Principal Investigator:||Adrian Handforth, M.D.||Veteran Affairs Greater Los Angeles|