Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease
Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Primary Lateral Sclerosis; Progressive Muscular Atrophy
Intervention: Levetiracetam (Biological)
Phase: Phase 2
Status: Completed
Sponsored by: Duke University Official(s) and/or principal investigator(s): Richard S Bedlack, MD, PhD, Principal Investigator, Affiliation: Duke University
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.
Clinical Details
Official title: A Pilot Trial of Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Safety and tolerability at 9 months of treatment.
Secondary outcome: Cramps scores, spasticity scores, FVC, ALSFRS, MMT
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with MNDs (ALS, PLS or PMA)who have cramps with average severity 50/100
points, are able to provide informed consent, have normal renal function and are on a
stable riluzole dose.
Exclusion Criteria:
- Pregnancy; unstable medical illness, dementia; drug abuse or non-compliance
Locations and Contacts
Duke University ALS Clinic - 932 Morreene Road, Durham, North Carolina 27705, United States
Additional Information
Starting date: May 2006
Last updated: June 17, 2013
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