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Recruiting NCT06532474

Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies

— Observational Spinal Muscular Atrophy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
This is an observational study: the protocol does not assign a study treatment.
Who it may be relevant to
Registry conditions: Spinal Muscular Atrophy. Basic parameters: 5 years — 20 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Pilot Study Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies

Overview

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.

Detailed description

This is an observational study to demonstrate the feasibility of performing MR functional imaging in exercising muscle in patients with SMA. The participants will be prescribed medication by their treating physician, they will not receive any drug as part of this study.

Participants participating in the ML43225 study, will be put into groups depending on their type of SMA and the drugs they may or may not be taking. They will be asked to come to clinic 3 times over one year. Each visit will include magnetic resonance (MR) studies, a muscle ultrasound, a nerve test, muscle function testing, lung function testing, blood work, vital signs, and participants will be asked about their quality of life and daily life activities. After participants have completed the 3 required visits, they will be taken off study.

Primary outcome measures

  • Feasibility of performing MR functional imaging in SMA patients [Time frame: At baseline and at 6 months (+/- 14 days)]
  • Reliability of performing MR functional imaging in SMA patients [Time frame: At baseline and at 6 months (+/- 14 days)]
  • 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)]
  • 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)]
  • 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)]
  • 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)]
Secondary outcome measures (12)
  • Identify changes in motor function in non-ambulant patients and ambulant patients with SMA types 2 and 3 [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in non-ambulant patients with SMA types 2 and 3 - Revised Upper Limb Module [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in non-ambulant patients with SMA types 2 and 3 - Block and Box Test [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in ambulant patients with SMA types 2 and 3 - 6-Minute Walk [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in ambulant patients with SMA types 2 and 3 - 10 Meter Walk/Run [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in ambulant patients with SMA types 2 and 3 - 4-Stair Climb [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in ambulant patients with SMA types 2 and 3 - Supine-to-Stand Test [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Identify changes in motor function in ambulant patients with SMA types 2 and 3 - Timed Up-and-Go Test [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Assess myometry, or measurement of muscle strength [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Muscle ultrasound thickness and echogenicity of 5 muscles - 2 upper limb and 3 lower limb [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Plasma neurofilament light (NF-L) and phosphorylated heavy chain (pNF-H) levels [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]
  • Blood SMN protein levels [Time frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days)]

Eligibility 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, 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model
Case-only

Study locations

United States · 1 center
  • St. Jude Children's Research Hospital — Memphis

Identifiers

NCT: NCT06532474 · ML43225

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗