Spinal Muscular Atrophy
Conditions
Keywords
Spinal Muscular Atrophy, Adult
Brief summary
The primary objective of this proposal is to determine whether oral VPA is effective in treating SMA in adult patients.
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.
Interventions
Drug: Valproic Acid and Levocarnitine; capsules
DRUGPlacebo
For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment
Sponsors
Families of Spinal Muscular Atrophy
Abbott
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Change in SMAFRS | 13 months |
| Change in distance walked in 6 minutes | 13 months |
| Change in time to climb four standard stairs | 13 months |
| Change in health-related QOL assessed through the modified sickness impact profile (SIP) | 13 months |
| Change in lean body mass through DEXA scanning | 13 months |
Countries
United States
Outcome results
None listed