NCT06532474 · St. Jude Children's Research Hospital
Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies
What this study is about
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.
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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.
Primary outcome measures
Feasibility of performing MR functional imaging in SMA patients
Time frame: At baseline and at 6 months (+/- 14 days)
MR functional imaging is considered feasible if ≥ 80% of MRI protocol eligible patients can complete 100% of imaging assessments at baseline and 6 months.
Reliability of performing MR functional imaging in SMA patients
Time frame: At baseline and at 6 months (+/- 14 days)
MR functional imaging is considered reliable if the test-retest reliability is ≥ 0.80 for key imaging biomarkers.
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (phosphocreatine)
Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
Real-time 31P MR spectroscopy and CrCEST MRI will be used to measure phosphocreatine within the muscles at rest, during an exercise protocol, and during post-exercise recovery to baseline. Both measure the recovery time in seconds.
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (creatine concentrations)
Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
Real-time 31P MR spectroscopy and CrCEST MRI will be used to measure creatine concentrations within the muscles at rest, during an exercise protocol, and during post-exercise recovery to baseline. Both measure the recovery time in seconds.
Measure intramuscular fat fraction in major muscle extremity in patients with SMA types 2 and 3
Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
Measurement of thickness of muscle compared to fat on MRI, measured in percentage.
Measure electrophysiological tests of motor neuron function to repetitive nerve stimulation in patients with SMA types 2 and 3
Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)
Electrophysiological testing: Compound motor action potential (CMAP, measured in millivolts), motor unit number estimate (MUNE, average 200-400 for most limb muscles), and repetitive stimulation at 3 Hz - right ulnar to abductor digiti minimus and right fibular/peroneal nerve to tibialis anterior muscle. A decrease of more than 40% in the amplitude of CMAP is considered abnormal.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 one year prior to screening
- Must have voluntarily decided to switch therapies based on discussion with their treating physician
- Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR
- Have never received any SMN-directed therapies (Group 4)
Exclusion criteria
- Any chronic medical condition, planned surgery, or treatment with a medication which would impact safety or participation of the study at the investigator's discretion
- Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
- Fat fraction \> 35% in calf or bicep at screening MRI
- Need for routine non-invasive ventilation support.
- Non-oral nutritional support, e.g., gastrostomy tube feeding.
- Any ferrous metal implants (e.g., spinal rods) that preclude testing in a MR scanner.
Where
- Memphis, Tennessee
Collaborators
Genentech, Inc.
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 9, 2026 · Source of record for eligibility and locations