Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis

This study has been completed.
Sponsor:
Collaborator:
Princess Beatrix Fund, The Netherlands
Information provided by:
UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00136110
First received: August 24, 2005
Last updated: April 30, 2007
Last verified: April 2007
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Sequential Clinical Trial of Sodium Valproate in ALS

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

ClinicalTrials.gov Identifier: NCT00136110     History of Changes
Other Study ID Numbers: 04/182-0
Study First Received: August 24, 2005
Last Updated: April 30, 2007
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)

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on August 26, 2014