Clinical trial NCT06374719: WiTNNess - TNNT1 Myopathy Natural History Study
Official title: WiTNNess: An International Natural History Study of Autosomal Recessive TNNT1 Myopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: TNNT1-associated Myopathy
Infantile-onset Nemaline Rod Myopathy
Myopathies, Nemaline
Myopathy
Myopathy, Rod
Myopathy; Hereditary
Amish Nemaline Myopathy
Nemaline Myopathy 5
NEM5
Genetic Muscle Disease
Recessive Hereditary Disorder (Autosomal)
ANM
Lead sponsor: Clinic for Special Children
Sponsor class: OTHER
First posted: 2024-04-19
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population includes anyone diagnosed with biallelic pathogenic variants of TNNT1

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Event-free survival
timeFrame: Day 1 up to 15 years
Secondary outcomes:
measure: Motor Milestones
timeFrame: All milestones normally achieved by postnatal age 17.1 months (normal 99th percentile reference value for independent walking).
measure: Thriving
timeFrame: Day 1 up to 15 years
Other outcomes:
Locations:
city: Gordonville
country: United States
facility: Clinic for Special Children
state: Pennsylvania
Study officials:
affiliation: Clinic for Special Children
name: Kevin Strauss, MD
role: PRINCIPAL_INVESTIGATOR
References: