Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis - Full Text View

Sponsors and Collaborators:	UMC Utrecht Princess Beatrix Fund, The Netherlands
Information provided by:	UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00136110

Purpose

The purpose of this study is to determine whether the use of sodium valproate is effective in slowing the disease progression in Amyotrophic Lateral Sclerosis.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis	Drug: Sodium Valproate	Phase III

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Drug Information available for: Divalproex sodium Valproic acid Valproate Sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Sequential Clinical Trial of Sodium Valproate in ALS

Further study details as provided by UMC Utrecht:

Primary Outcome Measures:

Survival

Secondary Outcome Measures:

The rate of decline of daily functioning

Enrollment:	165
Study Start Date:	April 2005
Study Completion Date:	February 2007

Detailed Description:

Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by progressive degeneration of motor neurons leading to muscle weakness.

The pathogenesis of ALS is unknown, but there is convincing evidence that several molecular mechanisms play a role. Previous studies investigated the role of the Survival Motor Neuron (SMN) gene in ALS. Recent data suggest that SMN genotypes producing less SMN protein increase susceptibility and severity of ALS. This leads to the hypothesis that the clinical expression of ALS is influenced by the total SMN protein level in affected patients. In a population of ALS patients in the Netherlands we found that SMN genotypes producing less SMN protein appear to increase susceptibility and severity of ALS. It was shown that the HDAC inhibitor sodium valproate (SVP) increases levels of SMN protein in vitro. From these results and from data suggesting neuroprotective properties of SVP, it is hypothesised that SVP could extend survival of patients with ALS. In addition, sodium valproate significantly prolonged the disease duration in the animal model for ALS, the SOD1 transgenic mouse. Given that SVP is a FDA-approved compound with well-known pharmacokinetic and toxicity profiles, it is an attractive candidate for a clinical trial in ALS patients.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Definite, probable, or probable-laboratory supported ALS according to the revised El Escorial World Federation of Neurology criteria.
Intake of riluzole 50 mg twice a day (bid)
A disease duration at inclusion of more than 6 months and less than 36 months [inclusive] (disease onset is defined as the date of first symptoms excluding muscle cramps and fasciculations)
Vital capacity (VC%) ≥ 70% of normal value (slow expiration, best of a minimum of three and a maximum of five measurements, with a respiratory function validly assessable and a spontaneous, non-assisted ventilation)
Ages 18 - 85 years (inclusive)
Capable of thoroughly understanding the trial information given; has signed the informed consent.

Exclusion Criteria:

Tracheostomy, tracheostomal ventilation of any type, non-invasive ventilation more than 16 hours/ day, or supplemental oxygen during the last three months prior to inclusion.
Any medical condition or intoxication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of ALS.
Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment.
Confirmed hepatic insufficiency or abnormal liver function (ASAT, ALAT greater than twice the upper limit of normal range).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00136110

Locations

Netherlands
UMC Utrecht
Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

UMC Utrecht

Princess Beatrix Fund, The Netherlands

Investigators

Study Chair:	Leonard H Van den Berg, MD, PhD	UMC Utrecht
Principal Investigator:	Sanne Piepers, MD	UMC Utrecht
Principal Investigator:	Sonja W De Jong, MD	UMC Utrecht

More Information

No publications provided

Study ID Numbers:	04/182-0
Study First Received:	August 24, 2005
Last Updated:	April 30, 2007
ClinicalTrials.gov Identifier:	NCT00136110 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:

ALS
Sodium Valproate
randomised trial
Amyotrophic Lateral Sclerosis (ALS)

Study placed in the following topic categories:

Neurotransmitter Agents
Tranquilizing Agents
Spinal Cord Diseases
Psychotropic Drugs
Central Nervous System Diseases
Central Nervous System Depressants
Sclerosis
Neurodegenerative Diseases

Antimanic Agents
Valproic Acid
Neuromuscular Diseases
Lou Gehrig's Disease
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Degenerative Motor System Disease
Anticonvulsants

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Spinal Cord Diseases
Physiological Effects of Drugs
Nervous System Diseases
Psychotropic Drugs
Central Nervous System Diseases
Central Nervous System Depressants
Enzyme Inhibitors
Sclerosis
Neurodegenerative Diseases

Antimanic Agents
Valproic Acid
Pharmacologic Actions
Pathologic Processes
Neuromuscular Diseases
Amyotrophic Lateral Sclerosis
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Motor Neuron Disease
Anticonvulsants

ClinicalTrials.gov processed this record on May 07, 2009