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Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00324454
First Posted: May 11, 2006
Last Update Posted: June 19, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Duke University
  Purpose
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
Motor Neuron Disease Amyotrophic Lateral Sclerosis Primary Lateral Sclerosis Progressive Muscular Atrophy Biological: Levetiracetam Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease

Resource links provided by NLM:


Further study details as provided by Duke University:

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

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

Enrollment: 20
Study Start Date: May 2006
Study Completion Date: June 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Levetiracetam
    Levetiracetam 1500 mg BID
    Other Name: Keppra 1500 mg BID
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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00324454


Locations
United States, North Carolina
Duke University ALS Clinic - 932 Morreene Road
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
UCB Pharma
Investigators
Principal Investigator: Richard S Bedlack, MD, PhD Duke University
  More Information

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00324454     History of Changes
Other Study ID Numbers: Pro00005846
8380-06-3R0 ( Other Identifier: DUMC )
First Submitted: May 9, 2006
First Posted: May 11, 2006
Last Update Posted: June 19, 2013
Last Verified: January 2009

Keywords provided by Duke University:
motor neuron disease
amyotrophic lateral sclerosis primary lateral
sclerosis; progressive muscular atrophy
cramps
spasticity

Additional relevant MeSH terms:
Sclerosis
Amyotrophic Lateral Sclerosis
Atrophy
Motor Neuron Disease
Muscle Spasticity
Muscular Atrophy
Muscular Atrophy, Spinal
Pathologic Processes
Pathological Conditions, Anatomical
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Piracetam
Anticonvulsants
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs