Establishing Walking-related Digital Biomarkers in Rare Childhood Onset Progressive Neuromuscular Disorders

Recruiting

• Conditions: Spinal Muscular Atrophy Type 3; Duchenne Muscular Dystrophy (DMD)

• Registration Number: NCT06839469
• Lead Sponsor: Columbia University

Brief Summary

The purpose of this research is (1) to identify disease specific walking-related digital biomarkers of disease severity, and (2) monitor longitudinal changes in natural environments, for extended periods of time, in DMD and SMA.

Detailed Description

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are genetic disorders that often result in progressive weakness and impaired function. Our recent findings suggest that novel machine-learning (ML)-based abstraction models may map noisy signals from foot-worn sensors (namely, instrumented insoles developed by the project team) into accurate and clinically relevant spatiotemporal and kinetic gait parameters. These gait parameters derived from instrumented insoles may serve as functional biomarkers to detect changes in real world function. All participants will be observed and measured while wearing the instrumented insoles in the lab and in real-life environments.

Study Timeline

• Study Start: 2024-05-01
• Status Verified: 2025-02
• Study First Submitted: 2025-02-17
• Study First Submitted QC: 2025-02-17
• Last Update Submitted: 2025-02-17
• Study First Posted: 2025-02-21
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-12-30
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

One of the following categories:

Genetic confirmation of disease (DMD, SMA) or healthy control Able to walk independently at least 25 meters

Cohort specific inclusion criteria include:

ongoing corticosteroids therapy or initiation of corticosteroid therapy in the previous 3 months for DMD stable dose of FDA approved SMN up-regulator therapy or in an open-label extension phase of a study treatment for at least 6 months for SMA or gene replacement at enrollment for SMA or DMD participants.

Exclusion Criteria

use foot orthoses or assistive devices for community ambulation or a mobility device for community navigation, use investigational medications intended for treatment of NMD within 30 days prior to study entry had an injury or surgery that would impact gait within the previous 3 months

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Six Minute Walk Test	One day	Participants will complete the six minute walk test in a corridor which includes the instrumented walkway, while wearing the insoles. This is to measure spatial parameters, kinetic parameters, temporal parameters, and metrics of cumulative activity in order to compare against the gold standard instrumented walkway. The six minute walk test is an objective evaluation of functional exercise capacity, and measures the maximum distance a person can walk in six minutes over a 25 meter course.
10 Meter Walk/Run	One day	Participants will walk, or run if able to, for 10 meters on the instrumented walkway while also wearing the insoles. This will be done to measure spatial parameters, kinetic parameters, temporal parameters, and metrics of cumulative activity in order to compare against the gold standard instrumented walkway. This outcome is reported as the time it takes for the participant to complete 10 meters as fast as possible.
Time Up and Go Test (TUG)	One day	Participants will complete the TUG test. This is a timed test of mobility, requiring the participant to stand up from a seated position, walk 3 meters and return to sitting in the chair. The outcome reported is the time it takes for the participant to complete the sequence.
Muscle Strength Testing with Hand-held Dynamometry (HHD)	One day	HHD is used to assess the strength of muscles and is reported as the maximum strength exerted in pounds (lbs).
30 Second Sit to Stand Test (30STS)	One day	30STS test is used to basic muscle power and function. The participant begins seated with their arms at their sides, feet flat on the floor and back against the chair. They are instructed to rise up to a full standing position and sit back down as many times as possible in 30 seconds, with or without using their hands for support.
Ankle Range of Motion	One day	Ankle range of motion (ROM) will be assessed on both the left right side using standardized goniometers. The procedures used will be standardized and performed by trained physical therapists who have attended in-person training. ROM will be recorded in degrees for plantar flexion and dorsiflexion.
Knee Extension Range of Motion	One day	Knee extension range of motion (ROM) will be assessed on both the left right side using standardized goniometers. The procedures used will be standardized and performed by trained physical therapists who have attended in-person training. ROM will be recorded in degrees of knee extension.
Hip Extension Range of Motion	One day	Hip extension range of motion (ROM) will be assessed on both the left right side using standardized goniometers. The procedures used will be standardized and performed by trained physical therapists who have attended in-person training. ROM will be recorded in degrees of hip extension.

Secondary Outcome Measures

Name	Time	Method
Free-living Testing of Instrumented Insoles	One month	To determine spatial parameters, kinetic parameters, temporal parameters, and metrics of cumulative activity using instrumented insoles, participants with SMA, DMD, and healthy controls will be asked to wear the insoles along with a validated activity tracker. Participants will be asked to wear the insoles during a single day visit to the lab, and then for at least 180 hours at home in a real-life environment. Participants will be asked to wear the insoles and activity tracker for at least 6 hours per day when at home. Compliance with this outcome will be measured in total hours the insoles are worn over the study period (one month).
Validation of Physical Activity using Actigraph accelerometer	One month	An Actigraph will be provided and worn during waking hours, while the participant is also wearing the insoles. Data extracted are counts per minutes, and are measurements of movement performed in both vertical and horizontal axis. The counts will be used to quantify the time the participant is inactive, low, moderate and / or in vigorous physical active.
International Physical Activity Questionnaire-Short Form, IPAQ-SF	One day	The IPAQ-SF is a self report questionnaire that assesses the types of intensity of physical activity and sitting time that people do as part of their daily lives. It is used estimate total physical activity in MET-min/week and time spent sitting in the 7 days prior to completing the questionnaire. It will be completed by participants aged 18 and over, at the start and at the end of the one-month insole wear time.
PROMIS Pediatric Physical Activity Questionnaire	One day	The pediatric activity questionnaire measures a child's self-report of short bouts of moderate to vigorous physical activity. This questionnaire is designed to measure constructs best recalled by children such as physiological response, symptoms, and short bouts of higher intensity activity. The questionnaire has an 8-item bank and is intended for use with children ages 8 to 17 years or with a parent proxy version for children aged 5 to 17 years. It will be completed at the start and at the end of the one month insole wear time and scores will calculated and range from 8-40.

Trial Locations

Locations (3)

Stanford University; 🇺🇸 Palo Alto, California, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States