Ambulatory Spinal Muscular Atrophy, Spinal Muscular Atrophy Type 3
Conditions
Keywords
spinal muscular atrophy, SMA, instrumented insole, bone health, fracture, bone mineral density, gait, low bone mass
Brief summary
The objective of this study is to understand how spatiotemporal and kinetic gait parameters are associated with bone health in pwSMA who are receiving DMT. We hypothesize that gait parameters are associated with BMD and can determine fracture risk in pwSMA. This is an observational study that involves one in-clinic visit (approximately 3 hours) with remote follow-up visits (approximately 15 minutes) every 3 months for 1 year to collect fracture and medical history. Each of the assessments included in this study are non-interventional and are not intended as a treatment nor are they at the level of standard of care.
Detailed description
Addressing bone health is a high priority and remains a concern for the SMA community despite the availability of DMTs. Fractures often have devastating, irrecoverable impacts on function, especially in ambulatory pwSMA. While the most recent standards of care for SMA recommend annual screening, supportive treatments are not recommended until there has been a fracture, a reactive approach which may not be enough to mitigate LBM. Implementing novel, wearable technology and machine learning (ML) models to identify fracture risk will lead to a proactive approach to manage bone health and attenuate the negative sequalae of fractures. This is an observational cross-sectional study of ambulatory children and adults with SMA. The aims of this study are to (1) Identify gait-related digital biomarkers of bone health in ambulatory pwSMA, (2) Determine the ability of digital biomarkers to differentiate between pwSMA with and without a history of fractures, and (3) Investigate the ability of risk profiles derived from the digital biomarkers to predict prospective fractures over one year.
Interventions
None listed
Sponsors
Jacqueline Montes
Biogen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of 5qSMA * Between 8 and 50 years of age * Able to walk 10 meters without support or an assistive device * All participants who meet the inclusion criteria regardless of treatment status will be included, including those on adjuvant therapies, whether investigational or approved
Exclusion criteria
* Injury or surgery within previous 3 months that would impact ability to perform in-clinic gait assessments * Unwilling or unable to comply with all study procedures * Age less than 8 or over 50 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dual X-Ray Absorptiometry (DXA) | Baseline | Bone mineral density (BMD), a measure of the mineral content in bones is assessed using dual x-ray absorptiometry (DXA). DXA can be used to identify individuals with low bone mass (LBM). DXA uses low-power x-ray and is a safe and reliable measure validated to diagnose osteoporosis. DXA provides a t-score and z-score so that based on age, low bone mass can be appropriately determined. DXA also provides a subtotal BMD score as well as scores specific to certain body regions, both of which will be utilized in the first aim. |
| Blood collection | Baseline | Blood will be collected to assess for routine markers related to bone mineral density. Blood will be tested for levels of calcium, vitamin D, bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTx). The amount of blood collected will be within hospital rules for children. The total amount of blood will be approximately 2 mL or 1/2 a teaspoon. BALP is a bone formation marker while CTx is a bone resorption marker. Calcium and vitamin D are known to be positively associated with BMD. |
| Fracture history | Baseline, months 3, 6, 9, and 12 | Details regarding lifetime fracture history will be collected via questioning at the in-clinic visit and during remote follow up visits, every three months for one year. The participant will be asked to describe each incident separately, including the age at fracture, mechanism of injury (how it happened, its nature, and force), any preceding events like falls or dizziness, and associated symptoms. Fractures will be characterized by location, type and treatment (surgical or conservative). |
| Fall history | Baseline, months 3, 6, 9 and 12 | Details regarding falls, that occurred within the past year, will be collected using a structured questionnaire at the in-clinic visit and during the one-year follow-up. Falls will be described by mechanism, environment and outcome. |
| Collection of spatiotempoal and kinetic gait parameters using instrumented insoles (AI-Sole) | Baseline | Stride-by-stride spatiotemporal and kinetic gait parameters will be collected with AI-Sole continuously during the 6MWT. Spatiotemporal parameters included stride length (SL), stride velocity (SV), percent time in stance phase (%St), and percent time in terminal double support (%DS). Kinetic parameters included the anteroposterior (AP-COP) and mediolateral (ML-COP) ranges of the center-of-pressure normalized by shoe size, as well as the Absolute COP-Cyclogram Asymmetry Index (\|ASI\|). |
| Six Minute Walk Test | Baseline | Participants will complete the six minute walk test in a corridor which includes the instrumented walkway, while wearing the insoles. This is to measure spatial parameters, kinetic parameters, temporal parameters, and metrics of cumulative activity in order to compare against the gold standard instrumented walkway. The six minute walk test is an objective evaluation of functional exercise capacity, and measures the maximum distance a person can walk in six minutes over a 25 meter course. |
| IPAQ-SF | Baseline | A quantitative assessment of usual physical activity will be captured using the International Physical Activity Questionnaire Short Form (IPAQ-SF).The IPAQ-SF is a commonly used self-administered questionnaire designed to obtain internationally comparable data on health-related physical activity. The IPAQ-SF is composed of seven questions from four domains of physical activity, including vigorous and moderate physical activity, walking physical activity, and sitting time. A weighted total from vigorous physical activity, moderate physical activity, and walking physical activity is calculated to produce a total amount of physical activity in MET-min/week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ten Meter Walk Run (10MWR) | Baseline | The 10MWR is an objective evaluation of function that measures the speed at which an individual can complete 10 meters. Gait speed is a commonly used indicator in NMD, and this test can be done by either walking or running. The 10MWR has been demonstrated to be safe to administer in individuals with SMA. |
| Timed Up and Go Test (TUG) | Baseline | The TUG test, a method to assess balance and mobility, measures the time it takes an individual to stand up from a chair, walk 3 meters, turn around, and sit down in the same chair. In SMA, TUG scores are associated with total leg and knee flexor strength, gross motor function, the 10-meter walk/run, and 6MWT. TUG test is a sensitive and reliable measure of functional impairment in inherited neuromuscular disorders. |
| 30 Second Sit to Stand (30-STS) | Baseline | The 30-STS test is used to evaluate basic muscle power and function. The participant is to complete as many sit-to-stands as possible, with or without using their hands for support, in 30 seconds. |
Countries
United States
Contacts
CONTACTCara Kanner, PT, DPT, EdD
Outcome results
None listed