Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients… (NCT06532474) | Clinical Trial Compass
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Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies
United States24 participantsStarted 2025-10-29
Plain-language summary
In this observational study, researchers are looking at the effects of spinal muscular atrophy (SMA) drugs on the muscles and nerve cells in patients with SMA.
Primary Objectives
* To evaluate the feasibility and reliability of performing MR functional imaging in exercising muscle in patients with SMA.
* To evaluate patients with SMA types 2 and 3 at baseline and longitudinally at 6 and 12 months
Secondary Objectives
* To describe the MR functional bioenergetics response in muscles in five potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), switching from Spinraza or Zolgensma to Evrysdi and initiating combination therapy of Spinraza or Zolgensma with Evrysdi .
* To identify changes in motor function in patients with SMA types 2 and 3 who initiate treatment with risdiplam.
* To obtain biomarkers in blood, urine, and muscle tissue to provide proof-of-concept support for risdiplam effect on skeletal muscle.
* To obtain quality of life and disability data from participants in this study.
Who can participate
Age range
5 Years – 20 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Genetic confirmation of SMA with homozygous deletion of SMN1 or compound heterozygous deletion/mutation of SMN1
* Two, three, or four copies of SMN2
* Age 5 to 20 years
* Non-ambulatory participants: maximum function sitting or standing with support, HFMSE score at screening between 10 and 45 points.
* Ambulatory participants: minimum function of independent walking, able to walk unassisted a minimum of 100 meters at screening, HFMSE score at screening between 40 and 66.
* SMN-directed therapy inclusion:
* Current Evrysdi prescription (Group 1)
* Must have Evrysdi prescription through their treating physician
* If initiating combined therapy using Evrysdi with Spinraza or Zolgensma, must have not started Evrysdi treatment OR
* Current Spinraza or Zolgensma prescription (Group 2)
* For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule
* For patients on Zolgensma, must have been dosed at least one year prior to screening
* Must have Spinraza or Zolgensma prescription through their treating physician OR
* Changing from Spinraza or Zolgensma to Evrysdi (Group 3)
* For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule
* For patients on Zolgensma, must have been dosed at least…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Feasibility of performing MR functional imaging in SMA patients
Timeframe: At baseline and at 6 months (+/- 14 days)
2
Reliability of performing MR functional imaging in SMA patients
Timeframe: At baseline and at 6 months (+/- 14 days)
3
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (phosphocreatine)
Timeframe: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
4
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (creatine concentrations)
Timeframe: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
5
Measure intramuscular fat fraction in major muscle extremity in patients with SMA types 2 and 3
Timeframe: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
6
Measure electrophysiological tests of motor neuron function to repetitive nerve stimulation in patients with SMA types 2 and 3
Timeframe: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)