Spinal Muscular AtrophyNCT05518773
Mechanisms and Treatment of Exercise Intolerance and Persistent Fatigue in Spinal Muscular Atrophy
An observational study of Spinal Muscular Atrophy, run by Columbia University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 8 to 55 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Observational
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2022to 14 Nov 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The study sample will include 34 ambulatory SMA patients, 17 currently treated with nusinersen, and 17 currently treated with risdiplam.
Who may be able to join
- 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
- risdiplam, or (2) nusinersen
- Able to walk independently at least 25 meters
- Able to tread a stationary cycle ergometer.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
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.
Read the detailed description
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.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Observational
- Keywords
- spinal muscular atrophy, neuromuscular disease, risdiplam, nusinersen, aerobic capacity, oxygen uptake, fatigue, near infrared spectroscopy, muscle ultrasound, exercise tolerance, six minute walk test, mitochondria mitophagy, mitochondria, exercise, cycle ergometry, SMA
- Medical subject headings
- Muscular Atrophy, Spinal, Neuromuscular Diseases, Fatigue, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
Observational
| Study group | Role | What they receive |
|---|---|---|
| Nusinersen treated | Children and adults who are currently treated with nusinersen for at least 6 months prior to enrollment. Receives: Other: Observational | |
| Risdiplam treated | Children and adults who are currently treated with risdiplam for at least 6 months prior to enrollment. Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak oxygen uptake
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).
Measured: Baseline
Secondary outcomes (3)
NIRS derived index of muscle oxygen extraction
Near Infrared Spectroscopy (NIRS) is a simple, non-invasive method to measure oxygen in muscle and other tissues in vivo.
Measured: Baseline
Distance walked during the Six Minute Walk Test (6MWT)
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.
Measured: Baseline
Leg muscle composition
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).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2022
- Study start15 Dec 2022
- Primary completion14 Nov 2025
- Study completion14 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacqueline Montes, Columbia University
- Investigators
- Jacqueline Montes, PT, EdD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05518773
- Sponsor's protocol ID
- AAAT5811
- Status last verified
- Nov 2025
- First submitted
- 24 Aug 2022
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms and Treatment of Exercise Intolerance and Persistent Fatigue in Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT05518773
- Acronym / sponsor ID
- AAAT5811
- Conditions
- Spinal Muscular Atrophy
- Keywords
- spinal muscular atrophy, neuromuscular disease, risdiplam, nusinersen, aerobic capacity, oxygen uptake, fatigue, near infrared spectroscopy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 14 Nov 2025 (actual)
- Study completion
- 14 Nov 2025 (actual)
- First posted
- 29 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nusinersen treated | – | Other: ObservationalChildren and adults who are currently treated with nusinersen for at least 6 months prior to enrollment. |
| Risdiplam treated | – | Other: ObservationalChildren and adults who are currently treated with risdiplam for at least 6 months prior to enrollment. |
Who may qualify
- Ages
- 8 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The study sample will include 34 ambulatory SMA patients, 17 currently treated with nusinersen, and 17 currently treated with risdiplam.
Key inclusion criteria (6 listed)
- 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
- Able to walk independently at least 25 meters
- Able to tread a stationary cycle ergometer.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObservationalObservational | Other | Nusinersen treated, Risdiplam treated |
Primary outcome
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).
3 secondary outcomes
NIRS derived index of muscle oxygen extraction
Time frame: Baseline
Distance walked during the Six Minute Walk Test (6MWT)
Time frame: Baseline
Leg muscle composition
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacqueline Montes, PT, EdD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Muscular Atrophy, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak oxygen uptake (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.