MVICT May Be Better, More Reliable Test Than 6MWT in Trials of Ambulant SMA Patients, Study Finds

Maximal voluntary isometric contraction testing (MVICT) may be a better outcome measure than the six-minute walking test (6MWT) in clinical trials involving people with spinal muscular atrophy who are able to walk without assistance, a study has found.

The study, “Outcome measures in a cohort of ambulatory adults with spinal muscular atrophy,” was published in Muscle & Nerve.

Spinal muscular atrophy (SMA) comprises a group of neurodegenerative disorders characterized by the gradual loss of motor neurons — the nerve cells responsible for controlling voluntary muscles — in the spinal cord, leading to muscle weakness and wasting.

The disorder is divided into several subtypes (ranging from type 0 to type 4), depending on the age of disease onset and symptom severity. Patients affected by the most severe forms of the disease are those that have an early onset — usually during fetal development (type 0) or shortly after birth (type 1).

In contrast, those with milder forms of SMA normally start experiencing their first symptoms during childhood or later.

“In children and adults with less severe SMA, however, the progression of disease is more variable and tends to plateau, presenting additional challenges when designing meaningful outcome measures for clinical trials,” the researchers wrote.

In a previous study, researchers reported the findings of a double-blind, placebo-controlled, Phase 2 trial called VALIANT (NCT00481013) that investigated the effects of valproic acid (VPA) in adults with SMA who were able to walk unaided.

“In that trial, there was no effect of VPA on the primary or secondary outcomes despite confirmation of a pharmacodynamic effect,” they noted. Pharmacodynamics studies how the body responds to a therapy.

The primary outcome, or goal, of this trial was to evaluate the change in muscle strength from the beginning of the study up to six months, as assessed by MVICT. Secondary outcomes included the change in distance walked in the 6MWT.

In this study, researchers from The Ohio State University Wexner Medical Center decided to revisit data from VALIANT to investigate whether MVICT (which measures muscle strength), or the 6MWT (which measures the distance a person is able to walk in six minutes) would be the best choice as a primary outcome measure in trials enrolling people with SMA who are able to walk without assistance.

The investigators analyzed and compared the test-retest reliability of MVICT and the 6MWT, as well as their relationship with other relevant clinical outcomes and biomarkers of disease.

All 33 patients who participated in VALIANT had completed MVICT, and 30 had completed the 6MWT.

Findings revealed that both tests had a good test‐retest reliability, with MVICT slightly better than the 6MWT.

Both tests were strongly correlated with the SMA‐Functional Rating Scale (a measure of motor function improvement), lean muscle mass, and the compound muscle action potentials (a measure of muscle conduction) of arm muscles.

However, correlations between MVICT and other clinical outcomes were slightly stronger than those seen between the 6MWT and the same outcome measures.

“Based on the data from this cohort, we believe MVICT and 6MWT are reliable and meaningful outcome measures for use in ambulatory adults with SMA,” the investigators said.

“MVICT may be superior given the slightly better test-retest reliability and closer associations with other outcomes and biomarkers of neuromuscular function,” they added. “Prospective, longitudinal studies of adults before and after receiving the new generation of SMN-targeted therapies should be designed with these findings in mind.”