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

Utah System of Higher Education (USHE)

Status and phase: Completed; Phase 2

Conditions: Spinal Muscular Atrophy

Treatments: Drug: Placebo; Drug: Valproic Acid (VPA)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00481013

2006H0249

Details and patient eligibility

About

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

Full 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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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33 participants in 2 patient groups, including a placebo group

1a

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

1b

Active Comparator group

Description:

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

Treatment:

Drug: Valproic Acid (VPA)