A Pilot Clinical Trial Of Memantine for Essential Tremor

This study has been completed.
Sponsor:
Collaborators:
Ralph M. Parsons Foundation
Forest Laboratories
Information provided by (Responsible Party):
Adrian Handforth, MD, VA Greater Los Angeles Healthcare System
ClinicalTrials.gov Identifier:
NCT00439699
First received: February 22, 2007
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to obtain information on whether or not the medication Memantine reduces tremor in persons with essential tremor and is well-tolerated.


Condition Intervention Phase
Essential Tremor
Drug: Memantine
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by VA Greater Los Angeles Healthcare System:

Primary Outcome Measures:
  • The degree of tremor at the end of the dose adjustment phase compared to baseline [ Time Frame: Six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: February 2007
Study Completion Date: December 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine
Tremor reduction
Drug: Memantine
Mematine administration

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 or older
  • Subject diagnosed with essential tremor affecting both upper extremities.
  • Subject has been diagnosed for at least one year with tremor that is troublesome, so that improvement of tremor would improve the quality of life.
  • Subject has tremor with a tremor rating scale severity of 2 to 4 in one or both upper extremities in the tremor rating scale during posture and/or kinesis.
  • Subject has not had satisfactory tremor response to at least one anti-tremor medication.
  • Subject is able to comply with all testing and follow-up visit requirements.
  • Subject is able to abstain from alcohol for at least 12 hours prior to each Study Visit and from caffeinated beverages on the day of the Visit.
  • Subject has voluntarily signed an informed consent in accordance with institutional policies.
  • Subject is either

    • Not taking medication for Essential Tremor and has not done so for at least 28 days prior to Visit 1.
    • Taking medication for Essential Tremor and has been taking a stable dose so for at least 28 days prior to Visit 1.

Exclusion Criteria:

  • Subject has progressive neurological disease other than Essential Tremor.
  • Subject has history of alcoholism or drug abuse within the past year.
  • Subject has history of mania, bipolar depressive disorder, schizophrenia, or other major psychiatric disorder.
  • Subject drinks more than 2 glasses of wine or equivalent per day in last 30 days.
  • Subject has received botulinum injection of the upper extremities in the past 6 months.
  • Subject is currently using investigational device.
  • Subject has taken an investigational drug within a clearance duration of 5 times the half-life of the investigational drug.
  • Subject is pregnant or a female of childbearing potential not using adequate contraception.
  • Subject has a medical condition likely to result in hospitalization.
  • Known allergy to memantine or amantadine.
  • Taking medication that alkalinizes the urine, such as carbonic anhydrase inhibitor or sodium bicarbonate.
  • Any disorder or condition that may interfere with the absorption, the distribution, or excretion of drugs.
  • Taking medication known to cause postural tremor, that in the clinical judgement of the investigator is contributing to the subject's tremor.
  • Receiving deep brain stimulation within two weeks prior to Visit 1 or has potential need for deep brain stimulation during the study.
  • Has received ablative thalamotomy or gamma knife thalamotomy within six months of study onset.
  • Tremor potentially due to head trauma, hyperthyroidism, cerebrovascular disease, multiple sclerosis, polyneuropathy, or family history of Fragile X syndrome.
  • Known renal disease with creatinine level outside normal range.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439699

Locations
United States, California
VA Greater Los Angeles
Los Angeles, California, United States, 90073
Sponsors and Collaborators
VA Greater Los Angeles Healthcare System
Ralph M. Parsons Foundation
Forest Laboratories
Investigators
Principal Investigator: Adrian Handforth, M.D. Veteran Affairs Greater Los Angeles
  More Information

No publications provided

Responsible Party: Adrian Handforth, MD, Assistant Chief, Neurology, VAMC, VA Greater Los Angeles Healthcare System
ClinicalTrials.gov Identifier: NCT00439699     History of Changes
Other Study ID Numbers: 0033
Study First Received: February 22, 2007
Last Updated: June 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by VA Greater Los Angeles Healthcare System:
Essential Tremor
Memantine
Clinical Trial

Additional relevant MeSH terms:
Tremor
Essential Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on August 27, 2014