Examining muscle responses in spinal muscular atrophy patients treated with specific therapies
Pilot Study Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies
This study is testing how different treatments for spinal muscular atrophy affect muscle and nerve responses in patients over a year.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 24 (estimated) |
| Ages | 5 Years to 20 Years |
| Sex | All |
| Sponsor | St. Jude Children's Research Hospital Academic / other |
| Locations | 1 site (Memphis, Tennessee) |
| Trial ID | NCT06532474 on ClinicalTrials.gov |
What this trial studies
This observational study investigates the effects of spinal muscular atrophy (SMA) drugs on muscle and nerve responses in patients with SMA. Participants will be grouped based on their SMA type and treatment status, and will undergo a series of assessments including MR imaging, muscle ultrasounds, and functional tests over the course of one year. The study aims to evaluate the feasibility of MR imaging in exercising muscle and to gather biomarkers that reflect the impact of treatments like risdiplam on skeletal muscle function.
Who should consider this trial
Good fit: Ideal candidates are patients aged 5 to 20 years with genetically confirmed SMA and specific functional abilities based on their treatment status.
Not a fit: Patients who do not have a genetic confirmation of SMA or those outside the specified age range may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could enhance understanding of how SMA therapies affect muscle function, potentially leading to improved treatment strategies.
How similar studies have performed: While this study employs established methodologies, the specific focus on MR imaging in SMA patients represents a novel approach in this context.
Eligibility criteria
Show full inclusion / exclusion criteria
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, never walked independently, still able to sit independently for 5 seconds at screening, with active ankle plantar flexion strength of at least 3 N with hand-held myometry and capable of performing repetitive maximal plantar flexion effort for 120 seconds. 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, ankle plantar flexion strength of at least 10 N with hand-held myometry and capable of performing repetitive maximal plantar flexion for 120 seconds. HFMSE score at screening between 40 and 60.
* SMN-directed therapy inclusion:
* Current Evrysdi prescription
* Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR
* Current Spinraza or Zolgensma prescription
* 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
* 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
Exclusion Criteria:
* Labs at screening that are abnormal and identified as clinically significant by the PI: CBC, and CMP, liver function tests (over twice the upper limit of normal), PT/PTT, urine protein of 2+ or greater.
* Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
* Treatment with a possible SMA-enhancing or mitochondrial-enhancing medication, unless discontinued within 3 months prior to screening: oral albuterol, hydroxyurea, phenylbutryate, valproic acid, creatine, l-carnitine, or other mitochondrial type supplement (riboflavin, lipoic acid, etc.). A daily multivitamin and Vitamin D supplement and intermittent inhaled albuterol are permitted if the dosage is unchanged during the study.
* 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 this trial is running
Memphis, Tennessee
- St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
Study contacts
- Principal investigator: Richard Finkel, MD — St. Jude Children's Research Hospital
- Study coordinator: Jean Laboe, RN
- Email: referralinfo@stjude.org
- Phone: 901-595-1693
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.