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

NCT ID: NCT05518773

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 34 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-12-15
• Study Completion Date: 2025-11-14

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.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Nusinersen treated

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

Observational

Intervention Type: OTHER

Observational

Risdiplam treated

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

Observational

Intervention Type: OTHER

Observational

Interventions

Observational

Observational

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Jacqueline Montes

Associate Professor of Rehabilitation and Regenerative Medicine, Rehab & Regenerative Med PT

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacqueline Montes, PT, EdD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAT5811

Identifier Type: -

Identifier Source: org_study_id