Characterizing Perceived Physical Fatigability in Nusinersen-treated SMA

Characterizing Perceived Physical Fatigability in Nusinersen-treated Adolescents and Adults: The SMA EFFORT

The purpose of this project is to investigate the utility of the SMA EFFORT, an SMA-specific patient-reported outcome measure, to assess perceived physical fatigability that is anchored to intensity and duration of activities. We aim to characterize perceived physical fatigability (PPF) in a diverse cohort of people with SMA (pwSMA) and evaluate the change of PPF before and after nusinersen dosing.

Study Overview

• Status: Recruiting
• Conditions: Spinal Muscular Atrophy
• Intervention / Treatment: Other: Observational

Detailed Description

Fatigue and fatigability are symptoms often experienced by people living with spinal muscular atrophy (pwSMA). Nusinersen is shown to extend survival and improve motor function, but fatigue and fatigability persist. Treated patients report changes in their ability to complete repetitive physical activities but a way for measuring this has not been created. While tests completed in the clinic by individuals with SMA highlight that fatigability is an important part of the SMA experience,we do not fully understand how pwSMA experience fatigability with everyday tasks. Anecdotal reports of pwSMA suggest a waning effect in endurance toward the end of their treatment window, however this change has not been measured.The SMA EFFORT is specifically designed for pwSMA and aims to better understand how they feel when completing daily physical activities.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Rafael Rodriguez-Torres, DPT; Phone Number: 3472877093; Email: rsr2157@cumc.columbia.edu
• Study Contact Backup: Name: Cara Kanner, DPT; Phone Number: 516-581-8150; Email: chy2112@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Jacqueline Montes, PT EdD; Phone Number: 2123058916; Email: jm598@cumc.columbia.edu
      • Contact: Rafael Rodriguez-Torres, DPT; Phone Number: 347-287-7093; Email: rsr2157@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

12 years and older, with genetic diagnosis of all types of 5qSMA, treated with nusinersen (12 or 28 mg) for at least 6 months, will be included.

Description

Inclusion Criteria:

1. All types of 5qSMA (homozygous deletion or point mutation of the SMN1 gene and any number of SMN2 copies)
2. Receiving a stable dosing regimen of 12 or 28 mg nusinersen for at least 6 months

Exclusion Criteria:

1. An injury or surgery within the previous 3 months that would impact their ability to perform in-clinic function and/or fatigability assessments
2. Enrolled in an ongoing clinical trial, or extension study, expanded access program, or long-term registry of an investigational or recently approved medication
3. Receiving adjuvant and/or dual therapy (e.g., muscle-targeted, NMJ, or symptomatic treatments)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Walkers; Participants with SMA who are able to walk without assistance.	Other: Observational; Observational
Sitters; Participants with SMA who are unable to walk without assistance, but are able to sit independently.	Other: Observational; Observational
Non-sitters; Participants with SMA who are unable to sit without assistance.	Other: Observational; Observational

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SMA EFFORT	The SMA EFFORT is a perceived physical fatigability patient-reported outcome measure (PROM) that provides a percent (PPF%) total score to each participant based on their participation over the past 30 days.	Baseline, 1 week, 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Revised Upper Limb Module (RULM)	The RULM is used to assess motor function of the shoulder, mid-level elbow, wrist, and hand.	Baseline
Hammersmith Functional Motor Scale Expanded (HFMSE)	The HFMSE is a 33-item scale designed to assess gross motor function in sitters and walkers with SMA.	Baseline
Six-Minute Walk Test (6MWT)	The 6MWT is an objective evaluation of functional exercise capacity which measures the maximum distance a person can walk in six minutes over a 25-meter linear course.	Baseline
Six-Minute Mastication Test (6MMT)	The 6MMT is a measure of chewing endurance in which the individual is asked to continuously chew on a chewing tube for a period of six minutes.	Baseline
Endurance Shuttle Box and Block Test (ESSBT)	The ESSBT is a test of upper limb function that has been adapted to assess performance fatigability in SMA.	Baseline
Endurance Shuttle Nine-Hole Peg Test (ESNHPT)	The ESNHPT is used to assess more distal, fine motor upper extremity performance fatigability.	Baseline

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Biogen
• Investigators: Principal Investigator: Jacqueline Montes, Pt, EdD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2025
• Primary Completion (Estimated): December 7, 2026
• Study Completion (Estimated): February 26, 2027

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: fatigue; exercise; spinal muscular atrophy; SMA; neuromuscular disease; fatigability; nusinersen
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Fatigue; Muscular Atrophy, Spinal; Neuromuscular Diseases; Motor Activity; Health Services Administration; Quality of Health Care; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Watchful Waiting
• Other Study ID Numbers: AAAV5804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No