Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy

NCT00481013 | Completed Phase 2 DMC

• 1 other identifier: 2006H0249
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; Adult

Outcome Measures

Primary Outcomes (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.

  13 months

Secondary Outcomes (9)

• Change in SMAFRS

  13 months

• Change in strength assessed by hand-held dynamometer

  13 months

• Change in MUNE and CMAP

  13 months

• SMN2 copy number

  13 months

• Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF)

  13 months

Study Arms (2)

1a

PLACEBO COMPARATOR

For six months, half of patients are randomized into placebo . After 6 months, all patients are on treatment.

Drug: Placebo

1b

ACTIVE COMPARATOR

Cohort 1b patients are randomized onto treatment. After 6 months, all patients are on drug.

Drug: Valproic Acid (VPA)

Interventions

Valproic Acid (VPA) DRUG

Drug: Valproic Acid and Levocarnitine; capsules

Also known as: Depakote, Carnitor

1b

Placebo DRUG

For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment

1a

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• Interest in participating and the ability to meet the study requirements.
• Women of child bearing age are required to be on birth control or abstain while participating in the study.

You may not qualify if:

• Non-ambulatory type 3 adults and all type 2 adults.
• Patients with co-morbid conditions that preclude travel, testing or study medications.
• 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.
• 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.
• Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for \> 12 hours/day
• 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
• 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.
• Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding.

Sponsors & Collaborators

• University of Utah: lead
• Families of Spinal Muscular Atrophy: collaborator
• Abbott: collaborator

Study Sites (1)

Ohio State University Medical Center, Dept. of Neurology

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Valproic Acid; Carnitine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines

Study Officials

• John T Kissel

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Sandra P Reyna, M.D.

  Families of Spinal Muscular Atrophy

  STUDY DIRECTOR

• Kathryn J Swoboda, M.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurology and Pediatrics

Study Record Dates

• First Submitted: May 30, 2007
• First Posted: June 1, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: November 1, 2010
• Last Updated: December 6, 2016

Record last verified: 2016-12

Locations

US (1)