Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00324454
• Other study ID #: Pro00005846
• Secondary ID: 8380-06-3R0
• Status: Completed
• Phase: Phase 2
• First received: May 9, 2006
• Last updated: June 17, 2013
• Start date: May 2006
• Est. completion date: June 2008

Study information

• Verified date: January 2009
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2008
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Muscle Spasticity
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Primary Lateral Sclerosis
• Progressive Muscular Atrophy
• Sclerosis

Intervention

Biological:
• Levetiracetam
Levetiracetam 1500 mg BID

Locations

Country	Name	City	State
United States	Duke University ALS Clinic - 932 Morreene Road	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	UCB Pharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability at 9 months of treatment.		9 months	No
Secondary	Cramps scores, spasticity scores, FVC, ALSFRS, MMT		9 months	No