Clinical Trial: Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Trial of Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease

Brief Summary: 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.

Detailed Summary:

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 P
Sponsor: Duke University

Current Primary Outcome: Safety and tolerability at 9 months of treatment. [ Time Frame: 9 months ]

Original Primary Outcome: Safety and tolerability at 9 months of treatment.

Current Secondary Outcome: Cramps scores, spasticity scores, FVC, ALSFRS, MMT [ Time Frame: 9 months ]

Original Secondary Outcome: Cramps scores, spasticity scores, FVC, ALSFRS, MMT

Information By: Duke University

Dates:
Date Received: May 9, 2006
Date Started: May 2006
Date Completion:
Last Updated: June 17, 2013
Last Verified: January 2009