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

NCT05518773 | Completed

• 1 other identifier: AAAT5811
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Spinal Muscular Atrophy

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline

Secondary Outcomes (3)

• NIRS derived index of muscle oxygen extraction

  Baseline

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

  Baseline

• Leg muscle composition

  Baseline

Other Outcomes (1)

• Relationship of muscle quality and function

  Baseline

Study Arms (2)

Nusinersen treated

Children and adults who are currently treated with nusinersen for at least 6 months prior to enrollment.

Other: Observational

Risdiplam treated

Children and adults who are currently treated with risdiplam for at least 6 months prior to enrollment.

Other: Observational

Interventions

Observational OTHER

Observational

Nusinersen treated; Risdiplam treated

Eligibility Criteria

• Age: 8 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study sample will include 34 ambulatory SMA patients, 17 currently treated with nusinersen, and 17 currently treated with risdiplam.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Neuromuscular Diseases; Fatigue; Motor Activity

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Jacqueline Montes, PT, EdD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Rehabilitation and Regenerative Medicine, Rehab & Regenerative Med PT

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 29, 2022
• Study Start: December 15, 2022
• Primary Completion: November 14, 2025
• Study Completion: November 14, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

US (1)