WiTNNess - TNNT1 Myopathy Natural History Study (WiTNNess)

WiTNNess: An International Natural History Study of Autosomal Recessive TNNT1 Myopathy

WiTNNess is designed to accurately document the natural course and variation of muscle disease caused by pathogenic changes of the TNNT1 gene. The primary aim of the study is to specify meaningful outcome measures for future clinical trials. WiTNNess is open to children and adults worldwide. Participants can choose to include their information once (cross-sectional cohort) or every few months (prospective cohort).

Study Overview

• Status: Recruiting
• Conditions: Myopathy; Myopathy; Hereditary; Myopathies, Nemaline; TNNT1-associated Myopathy; Infantile-onset Nemaline Rod Myopathy; Myopathy, Rod; Amish Nemaline Myopathy; Nemaline Myopathy 5; NEM5; Genetic Muscle Disease; Recessive Hereditary Disorder (Autosomal); ANM

Detailed Description

WiTNNess is an observational study that includes prospective and cross-sectional arms, both of which include people diagnosed with autosomal recessive TNNT1-associated muscle disease, commonly described as a form of infantile-onset (NEM5A) or childhood-onset (NEM5B) nemaline rod myopathy. The study's primary objective is to establish the nature and time course of disease outcomes under current treatment, so that these can later be compared to outcomes achieved with novel disease-modifying therapies (i.e., interventional trials).

Participants from all over the world are welcome to enroll in either arm of the WiTNNess study. Following appropriate consent, those in the prospective arm are followed long-term. Recurring assessments are performed at the participant's home, the Clinic for Special Children, or a partnering clinical site, depending on the individual's particular circumstances. Basic assessments include vital signs, a physical exam, documentation of motor milestones, growth measurements, and blood chemistry values. Participant's may also undergo non-invasive ultrasound of the heart (echocardiogram) and one or more chest radiographs.

Participants in the cross-sectional arm are contacted once after consent. Members of the WiTNNess study team partner with healthcare providers and family members to capture pertinent medical history, physical exam findings, growth metrics, and motor milestones at the time of contact.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Joelle Williamson, MPH; Phone Number: 7176879407; Email: jwilliamson@clinicforspecialchildren.org
• Study Contact Backup: Name: Justin Hersh; Phone Number: 7176879407; Email: jhersh@clinicforspecialchildren.org

Study Locations

• United States
  • Pennsylvania
    • Gordonville, Pennsylvania, United States, 17529
      • Recruiting
      • Clinic for Special Children
      • Contact: Joelle Wiliamson, MPH; Phone Number: 7176879407; Email: jwilliamson@clinicforspecialchildren.org
      • Contact: Justin Hersh; Phone Number: 7176879407; Email: jhersh@clinicforspecialchildren.org
      • Principal Investigator: Vincent J Carson, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population includes anyone diagnosed with biallelic pathogenic variants of TNNT1

Description

Inclusion Criteria:

• Diagnosed with biallelic pathogenic variants of TNNT1
• Infantile-onset or childhood-onset proximal weakness without confounding medical conditions that could effect muscle health.

Exclusion Criteria:

• Another known or suspected medical condition (genetic or acquired) that could potentially alter the natural disease course or otherwise interfere with completion of study procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Prospective; Participants in the prospective cohort are enrolled during early infancy, shortly after diagnosis, and followed longitudinally with repeated assessments until reaching the primary study outcome.
Cross-Sectional; Participants in the cross-sectional cohort enroll at any time after diagnosis and all study data are collected at a single time point.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	The primary outcome is time until death or permanent ventilatory support, defined as any invasive (e.g., tracheostomy) or non-invasive (e.g., bilevel positive airway pressure) mechanical ventilatory assistance for ≥16 hours daily during ≥14 consecutive days in the absence of a reversible clinical state.	Day 1 up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Milestones	Six motor milestones that include sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone, and walking alone, as defined by the Word Health Organization Multicentre Growth Reference Study.	All milestones normally achieved by postnatal age 17.1 months (normal 99th percentile reference value for independent walking).
Thriving	Maintain weight at ≥3rd WHO reference percentile for sex and age. The ability to swallow normally and maintain body weight equal to or greater than the WHO 3rd reference percentile for sex and age without requiring non-oral feeding support (i.e., nasogastric or gastrostomy tube).	Day 1 up to 15 years

Collaborators and Investigators

• Sponsor: Clinic for Special Children
• Investigators: Principal Investigator: Vincent J Carson, MD, Clinic for Special Children

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Myopathies, Structural, Congenital; Muscular Diseases; Myopathies, Nemaline; Nemaline myopathy 5
• Other Study ID Numbers: WiTNNess

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No