Nemaline Myopathy Clinical Research Network (NM-CTRN)

The goal of this study is to establish a research network to help define the natural disease history and clinical outcome measures for Nemaline Myopathy (NM).

Study Overview

• Status: Not yet recruiting
• Conditions: Nemaline Myopathy

Detailed Description

The long-term aim of this study is to incorporate these outcome measures into clinical trials for NM therapies. Outcome measures to be assessed will be dependent on the participant's age and functional status. Follow-up visits will be conducted either every 3 or 6 months, dependent on age, for a total of 3 years.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Carolina Tesi-Rocha, MD; Phone Number: 650-723-0993; Email: ctesiroc@stanford.edu
• Study Contact Backup: Name: Sarah Ismail, BSc; Phone Number: 650-460-4596; Email: sismail@stanford.edu

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E8
      • The Hospital for Sick Children
      • Contact: Ana Stosic, MSc; Phone Number: 416-648-6831; Email: ana.stosic@sickkids.ca
      • Contact: Jim Dowling, MD
      • Contact: Kimberley Amburgey, MSc
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University/Lucile Packard Children's Hospital
      • Contact: Sarah Ismail, BSc; Phone Number: 650-460-4596; Email: sismail@stanford.edu
      • Contact: Carolina Tesi-Rocha, MD
      • Contact: Tina Duong, PhD, PT
      • Contact: John W Day, MD, PhD
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Health
      • Contact: Christopher Mendoza; Email: christopher.mendoza2@nih.gov
      • Contact: Carsten Bonnemann, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
      • Contact: Aleah Pagan, BA; Phone Number: 617-919-7498; Email: aleah.pagan@childrens.harvard.edu
      • Contact: Alan Beggs, PhD
      • Contact: Leslie Hayes, MD
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Children's Research Hospital
      • Contact: Jean Laboe, MSN, RN; Phone Number: 901-595-1693; Email: jean.laboe@stjude.org
      • Contact: Richard Finkel, MD
  • Texas
    • Dallas, Texas, United States, 75207
      • UT Southwestern Medical Centre/Children's Health Dallas
      • Contact: Holly Lawrence, CCRC; Phone Number: 214-456-9561; Email: holly.lawrence@utsouthwestern.edu
      • Contact: Kaitlin Batley, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified through several sources. The primary source will be through our NM-CRN MDA care center network. Participants will also be recruited through the CMDIR and the Beggs Laboratory. Information regarding the study will be disseminated to all MDA clinics through the MDA website and via email to clinic directors. In addition, the study will advertised to families through A Foundation Building Strength, which maintains a patient information website and newsletter.

Description

Inclusion Criteria:

• 0-18 years of age at recruitment
• Confirmation of Nemaline Myopathy (pathogenic or likely pathogenic mutations in ACTA1 (AD) or NEB (AR)
• Patient and/or parent or legal guardian must be willing and able to provide informed consent

Exclusion Criteria:

• Clinically significant medical finding on the physical examination, other than NM, that the Investigator deems unsuitable for participation in and/or completion of the study procedures
• Any confirmed chronic or acute condition or disease affecting any system(s), which could interfere with the results of the study and/or the compliance with the study procedures. This will be subject to the clinical judgement of the Principal Investigator (PI)
• Participants of ongoing (interventional) clinical trials that assess the efficacy of potential treatments will be excluded
• Safety concerns

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Individuals with Nemaline Myopathy; All participants in the study will have a diagnosis of Nemaline Myopathy, with either a pathogenic or likely pathogenic mutation in ACTA1 (AD) or NEB (AR). Participants can be either ambulatory or non-ambulatory and must be between the ages of 0-18.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validate the change over 36 months using the Alberta Infant Motor Scale (AIMS) Score	The AIMS is a standardized tool used to assess a child's gross motor development in four positions: prone, supine, sitting, and standing. Percentile scores are given from 0-100, with higher percentiles representing higher motor function.	36 months
Validate the change over 36 months using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)	The CHOP-INTEND assesses a child's ability to move their body in a lying down position, supported sitting, and assisted rolling through 16 items.	36 months
Validate the change over 36 months using the Hammersmith Infant Neurological Examination Section 2 (HINE-2)	This is a 37-item measure of infant developmental motor milestones divided into the following categories: neurological examination, developmental milestones and behavioral scale, and state of consciousness. Scores for individual categories will be combined into a composite score.This will be performed in participants aged 0-24months. Scores are interpreted in relation to optimality scores and cut-off scores for the participant's age. Higher scores represented higher function.	36 months
Validate the change in 32-item Motor Function Measure (MFM32) Scale Score	This motor function assessment consists of 32 items organized in three dimensions: standing position and transfers, axial and limb proximal motor function, and limb distal motor function. Total scores are given between 0-100, with 0 indicating severe functional impairment and 100 indicating no functional impairment.	36 months
Change in Peabody Developmental Motor Scales (PDMS-3) Scale Score	This is used to measure various motor abilities in young children. Four types of normative scores are yielded: age equivalents, percentile ranks, subtest scaled scores, and composite index scores. Age equivalents are indexes of relative standing that translate subtest raw scores into motor ages. Percentiles provide the examiner with an index that is easily understood. Subtest scaled scores are based on a distribution having a mean of 10 and a standard deviation of 3. Composite indexes are based on a distribution with a mean of 100 and a standard deviation of 15. Higher scores indicate higher level of function.	36 months
Change in ambulation over 36 months as measured by the 10 meter walk (m/s).	This test measures the time taken for a participant to walk 10 metres as quickly and safely as possible. This will be performed in ambulatory participants aged 2 years and older.	36 months
Change in ambulation over 36 months as measured by the 6 Minute Walk Test	This is a measure of how far a participant can walk along a track in 6 minutes. This will be performed in ambulatory participants aged 5 years and older.	36 months
Change in respiratory function over 36 months as measured by spirometry, specifically the supine forced vital capacity (FVC).	This is a measure (% predicted) of the maximum amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible. This will be performed in participants aged 5 years and older.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle thickness of lower extremity muscles over 36 months as measured by muscle ultrasound.	This will be conducted in a subset of participants aged >5 years.	Baseline through month 36
Skin Biopsy (optional)	This optional outcome measure involves a one-time removal of three to four 2mm pieces of skin from one body site.	Baseline through month 36

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: A Foundation Building Strength
• Investigators: Principal Investigator: Alan Beggs, PhD, Boston Children's Hospital; Principal Investigator: John W Day, MD, PhD, Stanford University; Principal Investigator: Tina Duong, PT, PhD, Stanford University; Principal Investigator: Carolina Tesi-Rocha, MD, Stanford University; Principal Investigator: Leslie Hayes, MD, Boston Children's Hospital; Principal Investigator: Jim Dowling, MD, PhD, The Hospital for Sick Children; Principal Investigator: Richard Finkel, MD, St Jude Children's Hospital; Principal Investigator: Carsten Bonnemann, MD, PhD, National Institutes of Health (NIH); Principal Investigator: Kaitlin Batley, MD, UT SOUTHWESTERN medical CENTRE

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Observational study; Neuromuscular disease; Congenital myopathy; Nemaline rod
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Myopathies, Structural, Congenital; Muscular Diseases; Myopathies, Nemaline
• Other Study ID Numbers: 72180

Plan for Individual participant data (IPD)

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

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