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Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA)

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ClinicalTrials.gov Identifier: NCT00481013
Recruitment Status : Completed
First Posted : June 1, 2007
Last Update Posted : December 6, 2016
Families of Spinal Muscular Atrophy
Information provided by (Responsible Party):
Kathryn Swoboda, University of Utah

Brief Summary:
The primary objective of this proposal is to determine whether oral VPA is effective in treating SMA in adult patients.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: Valproic Acid (VPA) Drug: Placebo Phase 2

Detailed Description:

Participation in this study entails six visits and seven to eight blood draws over 13 months. Each visit entails a stay of two days and one night at the General Clinical Research Center (GCRC).

Subjects who live within driving distance will be allowed to participate in the study without an overnight stay through two consecutive outpatient visits. All subjects will be evaluated at two screening visits 2-4 weeks apart to determine eligibility for participation. Eligible subjects will be randomized to receive VPA or placebo for the first six months. At the six-month visit, patients will be evaluated and crossed over to the other regimen.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective Controlled Trial of Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA) Study
Study Start Date : July 2007
Actual Primary Completion Date : December 2009
Actual Study Completion Date : November 2010

Arm Intervention/treatment
Placebo Comparator: 1a
For six months, half of patients are randomized into placebo . After 6 months, all patients are on treatment.
Drug: Placebo
For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment

Active Comparator: 1b
Cohort 1b patients are randomized onto treatment. After 6 months, all patients are on drug.
Drug: Valproic Acid (VPA)
Drug: Valproic Acid and Levocarnitine; capsules
Other Names:
  • Depakote
  • Carnitor

Primary Outcome Measures :
  1. The primary outcome for the study is change in muscle strength from baseline to six months in muscle strength as assessed by MVICT using a fixed testing system. [ Time Frame: 13 months ]

Secondary Outcome Measures :
  1. Change in SMAFRS [ Time Frame: 13 months ]
  2. Change in strength assessed by hand-held dynamometer [ Time Frame: 13 months ]
  3. Change in MUNE and CMAP [ Time Frame: 13 months ]
  4. SMN2 copy number [ Time Frame: 13 months ]
  5. Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF) [ Time Frame: 13 months ]
  6. Change in lean body mass through DEXA scanning [ Time Frame: 13 months ]
  7. Change in distance walked in 6 minutes [ Time Frame: 13 months ]
  8. Change in time to climb four standard stairs [ Time Frame: 13 months ]
  9. Change in health-related QOL assessed through the modified sickness impact profile (SIP) [ Time Frame: 13 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Ambulatory adults with SMA 3 ages 18-60. The diagnosis of SMA must be documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder. Patients must be able to walk thirty feet without assistance (i.e. no canes, walkers).
  2. Interest in participating and the ability to meet the study requirements.
  3. Women of child bearing age are required to be on birth control or abstain while participating in the study.

Exclusion Criteria:

  1. Non-ambulatory type 3 adults and all type 2 adults.
  2. Patients with co-morbid conditions that preclude travel, testing or study medications.
  3. Patients who have participated in a treatment trial for SMA in the 3 months prior to this trial, or plan on enrolling in any other treatment trial during the duration of this trial.
  4. Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing.
  5. Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for > 12 hours/day
  6. Transaminases, amylase or lipase > 3.0 x normal values, WBC < 3.0 or neutropenia < 1.0, platelet count < 100 K, or hematocrit < 30 persisting over a 30 day period
  7. Use of medications or supplements which interfere with VPA metabolism and increase the potential risks of the medications, or are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders within 3 months of study enrollment. These agents include riluzole, creatine, butyrate derivatives, growth hormone, anabolic steroids, daily albuterol use, anticonvulsants, or other HDAC inhibitors.
  8. Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding.

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): NCT00481013

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United States, Ohio
Ohio State University Medical Center, Dept. of Neurology
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
University of Utah
Families of Spinal Muscular Atrophy
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Principal Investigator: John T Kissel Ohio State University
Study Director: Sandra P Reyna, M.D. Families of Spinal Muscular Atrophy
Principal Investigator: Kathryn J Swoboda, M.D. University of Utah
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Responsible Party: Kathryn Swoboda, Associate Professor, Neurology and Pediatrics, University of Utah
ClinicalTrials.gov Identifier: NCT00481013    
Other Study ID Numbers: 2006H0249
First Posted: June 1, 2007    Key Record Dates
Last Update Posted: December 6, 2016
Last Verified: December 2016
Keywords provided by Kathryn Swoboda, University of Utah:
Spinal Muscular Atrophy
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Valproic Acid
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