Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy

Spinal Muscular Atrophy Clinical Trial

— VALIANTSMA  

Official title:

Prospective Controlled Trial of Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00481013
• Other study ID #: 2006H0249
• Status: Completed
• Phase: Phase 2
• First received: May 30, 2007
• Last updated: December 5, 2016
• Start date: July 2007
• Est. completion date: November 2010

Study information

• Verified date: December 2016
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Drug:
• Valproic Acid (VPA)
Drug: Valproic Acid and Levocarnitine; capsules
• Placebo
For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment

Locations

Country	Name	City	State
United States	Ohio State University Medical Center, Dept. of Neurology	Columbus	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
University of Utah	Abbott, Families of Spinal Muscular Atrophy

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in SMAFRS		13 months	No
Secondary	Change in strength assessed by hand-held dynamometer		13 months	No
Secondary	Change in MUNE and CMAP		13 months	No
Secondary	SMN2 copy number		13 months	No
Secondary	Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF)		13 months	No
Secondary	Change in lean body mass through DEXA scanning		13 months	No
Secondary	Change in distance walked in 6 minutes		13 months	No
Secondary	Change in time to climb four standard stairs		13 months	No
Secondary	Change in health-related QOL assessed through the modified sickness impact profile (SIP)		13 months	No