Amish Nemaline Myopathy, ANM, Genetic Muscle Disease, Infantile-onset Nemaline Rod Myopathy, Myopathies, Nemaline, Myopathy, Myopathy; Hereditary, Myopathy, Rod, NEM5, Nemaline Myopathy 5, Recessive Hereditary Disorder (Autosomal), TNNT1-associated Myopathy
Conditions
Brief summary
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).
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.
Interventions
None listed
Sponsors
Clinic for Special Children
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | Day 1 up to 15 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor Milestones | All milestones normally achieved by postnatal age 17.1 months (normal 99th percentile reference value for independent walking). | 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. |
| Thriving | Day 1 up to 15 years | 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). |
Countries
United States
Contacts
CONTACTJustin Hersh
CONTACTJoelle Williamson, MPH
PRINCIPAL_INVESTIGATORVincent J Carson, MD
Clinic for Special Children
Outcome results
None listed