Spinal Muscular Atrophy (SMA)
Conditions
Keywords
spinal muscular atrophy, Survival Motor Neuron protein (SMN), Neurofilament (NF), transcranial magnetic stimulation (TMS)
Brief summary
There is a general physiological rule that any organ or system needs some minimal amount of activity to prevent its atrophy or degeneration. Although the relevance of that rule to exercises in neuromuscular patients and for SMA in particular is not definitely proven, clinical observations seem to support this assumption. Also there are several experimental studies which provide additional support for utility of exercise for SMA. However, making regular exercises may be very challenging with SMA not only due to physical limitations, but due to psychological either. While being considered as safe and well tolerated intervention, TMS is able to mimic effects of real physical exercises, at least at the level of low motoneuron, it also provides several advantages. For example, possibility to exercise non-collaborative infants, minimization of psychological motivation impact in adults and/or ability to involve very weak muscle groups.
Interventions
High-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex (M1) of the limbs, delivered at a frequency above 5 Hz and an intensity of 90-100% of the resting motor threshold, across 10 sessions with up to 2400 stimuli per session, is a standard intervention used in various neurological disorders. However, its effects have not been studied in patients with spinal muscular atrophy (SMA).
DIAGNOSTIC_TESTlumbar puncture
Cerebrospinal fluid sampling to measure SMN protein and neurofilament concentrations before and after the TMS intervention.
Sponsors
P.V. Voloshyn Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine
Charitable Foundation Children with Spinal Muscular Atrophy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of 5q-autosomal recessive SMA confirmed by DNA test. * Informed consent. * A minimum score of 1 for Entry Item A of the Revised Upper Limb Module (RULM) scale for SMA: Can use hands to hold pencil or pick up a coin/token or drive a powered chair, use phone key pad
Exclusion criteria
* Subject has severe joint contractures that would affect ability to perform study measures, determined by the study physician. * Subject has a deconditioned respiratory system, per the discretion of the physician investigator. * Subject has behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in the Motor Function Measure Scale | The first assessment will be conducted before the initial TMS session, and the second will be performed one to two days after the final TMS session. | Motor Function Measure (MFM) scale measurement before and after TMS sessions |
| Change from Baseline of the Revised Upper Limb Module | The first assessment will be conducted before the initial TMS session, and the second will be performed one to two days after the final TMS session. | Revised Upper Limb Module (RULM) scale measurement before and after TMS sessions |
| Change from Baseline of the Hammersmith Functional Motor Scale - Expanded | The first assessment will be conducted before the initial TMS session, and the second will be performed one to two days after the final TMS session. | Hammersmith Functional Motor Scale - Expanded (HFMSE) measurement before and after TMS sessions |
| Change from Baseline in the 6-Minute Walk Test | The first assessment will be conducted before the initial TMS session, and the second will be performed one to two days after the final TMS session. | 6-Minute Walk Test (6MWT) measurement before and after TMS sessions |
Countries
Ukraine
Contacts
Primary ContactVitaliy M Matyushenko
Backup ContactAndriy V Shatillo, MD, PhD
Outcome results
None listed