Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis

• ClinicalTrials.gov Identifier: NCT00136110
• Recruitment Status: Completed
• First Posted: August 26, 2005
• Last Update Posted: May 1, 2007
• Sponsor: UMC Utrecht
• Collaborator: Princess Beatrix Muscle Foundation
• Information provided by: UMC Utrecht

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Sodium Valproate	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Sequential Clinical Trial of Sodium Valproate in ALS
• Study Start Date: April 2005
• Actual Study Completion Date: February 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Survival

Secondary Outcome Measures :

1. The rate of decline of daily functioning

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Netherlands

UMC Utrecht

Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

UMC Utrecht

Princess Beatrix Muscle Foundation

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Piepers S, Veldink JH, de Jong SW, van der Tweel I, van der Pol WL, Uijtendaal EV, Schelhaas HJ, Scheffer H, de Visser M, de Jong JM, Wokke JH, Groeneveld GJ, van den Berg LH. Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis. Ann Neurol. 2009 Aug;66(2):227-34. doi: 10.1002/ana.21620.

• ClinicalTrials.gov Identifier: NCT00136110
• Other Study ID Numbers: 04/182-0
• First Posted: August 26, 2005
• Last Update Posted: May 1, 2007
• Last Verified: April 2007

Keywords provided by UMC Utrecht:

ALS; Sodium Valproate; randomised trial; Amyotrophic Lateral Sclerosis (ALS)

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Valproic Acid; Anticonvulsants; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; GABA Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs