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Sponsors and Collaborators: |
Duke University UCB |
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Information provided by: | Duke University |
ClinicalTrials.gov Identifier: | NCT00324454 |
Levetiracetam (Keppra) is used to treat partial onset seizures. Its biological effects suggest it might also be useful in treating 3 aspects of human motor neuron diseases (MNDs) for which no effective therapy exists: cramps, spasticity, and disease progression.
Condition | Intervention | Phase |
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Motor Neuron Disease Amyotrophic Lateral Sclerosis Primary Lateral Sclerosis Progressive Muscular Atrophy |
Biological: Levetiracetam |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Pilot Trial of Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease |
Enrollment: | 20 |
Study Start Date: | May 2006 |
Estimated Study Completion Date: | June 2008 |
Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
Cramps in MNDs are believed to occur as a result of high-frequency burst firing of alpha motor neurons. Levetiracetam inhibits burst firing in epileptic rat hippocampus. Levetiracetam has never been tested against cramps in humans; however, it has helped another condition believed to result from burst firing of a motor nerve: hemi-facial spasm.
The mechanisms underlying spasticity in MNDs likely involve imbalance between excitatory and inhibitory influences on the alpha motor neurons. Levetiracetam may modulate these influences in a number of ways, including reducing the effects of zinc and beta-carbolines in GABA and glycine receptors. Levetiracetam reduces phasic (but not tonic) spasticity in patients with multiple-sclerosis.
Levetiracetam may have neuroprotective properties. In a model of cerebral ischemia induced by occlusion of the rat internal carotid artery, pre-treatment with levetiracetam reduced infarct size in a dose-dependent manner. In rats injected with kainic acid to induce calcium overload, oxidative stress and neurotoxicity, pretreatment with levetiracetam offset kainic acid's effects. The mechanisms for these effects may relate to levetiracetam's ability to influence calcium currents, or its ability to increase the release of growth factors from astrocytes, mechanisms that would be relevant in MNDs. Levetiracetam's ability to inhibit histone deacetylase may also help slow MNDs progression.
OBJECTIVES: 1. Assess the safety and tolerability of levetiracetam over 9 months in patients with MNDs. 2. Determine whether treatment with levetiracetam is associated with a reduction in cramps, spasticity or motor neuron disease progression.
METHODS:Open-label, Phase 2 trial of 20 adult patients with MNDs (ALS, PLS or PMA) at Duke University ALS Clinic. Eligible patients have cramps with average severity 50/100 points, are able to provide informed consent, have normal renal functions and are on a stable riluzole dose. Exclusions include pregnancy, unstable mental illness, dementia, drug abuse or non-compliance. The first 3 months of the study are a baseline period. Over the remaining 9 months, patients take levetiracetam at increasing doses up to 3000mg per day. Outcome measures include adverse events, tolerability,cramp-pain-severity score, cramp-frequency score, modified Ashworth Spasticity Score, Penn Spasm Score, FVC, ALSFRS-R and MMT.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, North Carolina | |
Duke University ALS Clinic - 932 Morreene Road | |
Durham, North Carolina, United States, 27705 |
Principal Investigator: | Richard S Bedlack, MD, PhD | Duke University |
Responsible Party: | Duke University ( Richard Bedlack, MD, PhD ) |
Study ID Numbers: | 8380-06-3R0 |
Study First Received: | May 9, 2006 |
Last Updated: | August 13, 2008 |
ClinicalTrials.gov Identifier: | NCT00324454 |
Health Authority: | United States: Institutional Review Board |
motor neuron disease amyotrophic lateral sclerosis primary lateral sclerosis; progressive muscular atrophy cramps spasticity |
Pathological Conditions, Anatomical Spinal Cord Diseases Spinal muscular atrophy Central Nervous System Diseases Sclerosis Degenerative motor system disease Muscle Cramp Neurodegenerative Diseases Motor neuron disease Progressive spinal muscular atrophy Signs and Symptoms |
Muscle Spasticity Amyotrophic lateral sclerosis Neuromuscular Diseases Amyotrophic Lateral Sclerosis Muscular Atrophy, Spinal Neurologic Manifestations Etiracetam Lou Gehrig's disease Atrophy Motor Neuron Disease Muscular Atrophy |
Nootropic Agents Neuromuscular Manifestations Pathologic Processes Therapeutic Uses |
Nervous System Diseases Central Nervous System Agents Pharmacologic Actions Anticonvulsants |