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Completed

NCT Number: NCT05518773

Mechanisms and Treatment of Exercise Intolerance and Persistent Fatigue in Spinal Muscular Atrophy

This study will focus on the pathophysiological underpinnings of reduced exercise capacity and fatigue in ambulatory patients with spinal muscular atrophy (SMA). There has been laboratory evidence to suggest that the molecular mechanisms underlying mitochondrial biogenesis may be vulnerable to survival motor neuron (SMN) protein deficiency. This is an observational, single visit study including 34 ambulatory SMA patients treated with SMN repletion therapies (risdiplam or nusinersen) for at least 6 months at enrollment.

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Key information

Conditions

Spinal Muscular Atrophy Behavior Central Nervous System Diseases Fatigue Motor Activity Motor Neuron Disease Muscular Atrophy, Spinal Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Spinal Cord Diseases

Age range

8 year–55 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Columbia University Irving Medical Center

New York, 10032, United States

About this study

SMN depletion affects muscle mitochondria and thus muscle function as a result. The relationship between these and their effect(s) on fatigue in the context of SMN repletion treatment has not been evaluated. If muscle function is vulnerable to SMN insufficiency, treatment strategies targeting muscle in addition to the central nervous system (motor neurons) may ameliorate fatigue and improve exercise capacity, thereby improving quality of life and bringing SMA treatments closer to a cure. This project explores such an idea by comparing the effects of the two different SMN repletion modalities in patients. This is an observational cross-sectional study involving ambulatory SMA children and adults treated for at least 6 months with SMN repletion therapy, either (1) systemically with risdiplam, or (2) intrathecally (central nervous system-only), with nusinersen.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Genetic confirmation of SMA with laboratory documentation of homozygous deletion of survival motor neuron (SMN1) exon 7;
  • At least 8 years of age at time of signing Informed Consent Form (or assent)
  • Children or adults currently receiving treatment, for at least 6 months, with SMN repletion therapy, either with

(1) risdiplam, or (2) nusinersen

  • Able to walk independently at least 25 meters
  • Able to tread a stationary cycle ergometer.

Exclusion criteria

  • Unable to walk 25 meters independently.
  • Use of investigational medications intended for the treatment of SMA within 30 days prior to study entry.
  • The presence of any contraindication to exercise according the American College of Sports Medicine (ACSM) criteria.

Treatment and study plan

Observational

Other

Observational

Primary outcomes

  1. Peak oxygen uptake

    Time frame: Baseline

    Participants will undergo an exercise tolerance test performed by a clinical exercise physiologist using an electronically-braked recumbent cycle ergometer to determine peak oxygen uptake (VO2 max).

Secondary outcomes

  1. NIRS derived index of muscle oxygen extraction

    Time frame: Baseline

    Near Infrared Spectroscopy (NIRS) is a simple, non-invasive method to measure oxygen in muscle and other tissues in vivo.

  2. Distance walked during the Six Minute Walk Test (6MWT)

    Time frame: Baseline

    6MWT is an objective evaluation of functional exercise capacity, measures the maximum distance a person can walk in six minutes over a 25-meter linear course.

  3. Leg muscle composition

    Time frame: Baseline

    To characterize leg muscle composition, quality and architecture using MRI and ultrasound in individuals with SMA treated with agents that restore SMN either systemically (risdiplam) or to central nervous system alone (nusinersen).

Other outcomes

  1. Relationship of muscle quality and function

    Time frame: Baseline

    Muscle quality and architecture will be assessed using MRI and muscle ultrasound of the lower body, and the relationship to strength, function, and fitness will be evaluated.

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Aug 29, 2022
Registry last updated
Dec 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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