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

This study has been completed.
Families of Spinal Muscular Atrophy
Information provided by (Responsible Party):
University of Utah Identifier:
First received: May 30, 2007
Last updated: January 13, 2015
Last verified: January 2015
The primary objective of this proposal is to determine whether oral VPA is effective in treating SMA in adult patients.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: Valproic Acid (VPA)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective Controlled Trial of Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA) Study

Resource links provided by NLM:

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in SMAFRS [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in strength assessed by hand-held dynamometer [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in MUNE and CMAP [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • SMN2 copy number [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF) [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in lean body mass through DEXA scanning [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in distance walked in 6 minutes [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in time to climb four standard stairs [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Change in health-related QOL assessed through the modified sickness impact profile (SIP) [ Time Frame: 13 months ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: July 2007
Study Completion Date: November 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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.
  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 identifier: NCT00481013

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
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
  More Information

Responsible Party: University of Utah Identifier: NCT00481013     History of Changes
Other Study ID Numbers: 2006H0249 
Study First Received: May 30, 2007
Last Updated: January 13, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
Spinal Muscular Atrophy

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathological Conditions, Anatomical
Signs and Symptoms
Valproic Acid
Antimanic Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents processed this record on May 22, 2016