Oxidative Capacity and Exercise Tolerance in Ambulatory SMA

Evaluation of Oxidative Capacity and Exercise Tolerance in Ambulatory Patients With Spinal Muscular Atrophy (SMA)

This proposal will focus on (1) estimating oxidative capacity of specific muscle groups during exercise using near infrared spectroscopy and (2) describing body composition to better understand exercise capacity and mitochondrial function in ambulatory spinal muscular atrophy (SMA) patients and disease controls. It is a 6-month observational study including 14 ambulatory SMA patients, 14 ambulatory patients with mitochondrial myopathy, and 14 healthy controls.

Study Overview

• Status: Completed
• Conditions: Spinal Muscular Atrophy Type 3; Mitochondrial Myopathy

Detailed Description

Spinal Muscular Atrophy (SMA) is a progressive, recessively-inherited neuromuscular disease characterized by weakness and muscle atrophy due to the loss of spinal cord motor neurons. The results from this study would provide preliminary data, using non-invasive methods, on oxidative capacity in ambulatory SMA patients and disease controls to aid in the design of exercise intervention studies. Furthermore, this information would link previous laboratory and preclinical findings of mitochondrial depletion in SMA to the clinical condition and provide important information for future studies designed to improve oxidative capacity and fitness in SMA patients.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 55 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study sample will include 14 ambulatory SMA patients, 14 ambulatory mitochondrial myopathy patients, and 14 healthy controls.

Description

Inclusion Criteria:

1. One of the following categories:

   • Genetic confirmation of SMA with laboratory documentation of homozygous deletion of SMN1 exon 7;
   • Genetic confirmation of mitochondrial myopathy or evidence from muscle biopsy confirming the diagnosis; or
   • Healthy individuals.
2. Able to walk independently at least 25 meters, and able to tread a stationary cycle ergometer.

Exclusion Criteria:

1. Unable to walk 25 meters independently.
2. Use of investigational medications intended for the treatment of SMA within 30 days prior to study entry.
3. The presence of any contraindication to exercise according the ACSM criteria.

Patients with and without Spinraza treatment are eligible.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
spinal muscular atrophy; ambulatory children and adults ages between 8 and 55 years old by the time of enrollment with laboratory documentation of homozygous deletion of SMN1 exon 7
mitochondrial myopathy; ambulatory children and adults ages between 8 and 55 years old by the time of enrollment with genetic confirmation or evidence from muscle biopsy confirming the diagnosis
control; The healthy control group will be age and gender-matched to the SMA and mitochondrial myopathy groups as best as possible.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 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.	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak oxygen uptake (V02 max)	Participants will undergo an exercise stress test performed by a clinical exercise physiologist using an electronically-braked recumbent cycle ergometer to determine peak oxygen uptake (VO2 max).	baseline, 6 months
Change in 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.	baseline, 6 months
Change in Lean body mass assessed with Dual Energy X-ray Absorptiometry (DEXA)	Dual-Energy X-ray Absorptiometry (DEXA) is a method of estimating bone and lean body mass by comparing the absorption of two distinct energy level beams at 46.8 keV and 80 keV, which are effective at differentiating soft tissue and bone. A standard DEXA scan will be performed in supine.	baseline, 6 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Muscular Dystrophy Association

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): October 1, 2020
• Study Completion (ACTUAL): January 1, 2021

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (ESTIMATE): September 12, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: exercise; mitochondria; exercise tolerance; spinal muscular atrophy; SMA; ambulation; near infrared spectroscopy; neuromuscular disease; cycle ergometry; mitochondrial myopathy; six minute walk test; oxidative capacity
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Mitochondrial Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Diseases; Muscular Atrophy, Spinal; Mitochondrial Myopathies
• Other Study ID Numbers: AAAQ9447; 1K01HD084690-01A1 (NIH)

Plan for Individual participant data (IPD)

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