Understanding genetic and physical aspects of childhood nerve and muscle disorders

Clinical and Molecular Manifestations of Neuromuscular and Neurogenetic Disorders of Childhood

This study is trying to learn more about the genetic and physical traits of childhood nerve and muscle disorders by looking at affected kids, their families, and healthy volunteers.

Quick facts

• Study type: Observational
• Enrollment: 5650 (estimated)
• Ages: 1 Day to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01568658 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the genetic and physical characteristics of childhood-onset nerve and muscle disorders, including muscular dystrophies and inherited neuropathies. Researchers will enroll affected individuals, their family members, and healthy volunteers to gather comprehensive data on the natural history and mechanisms of these disorders. The study will utilize various diagnostic tools, including medical history evaluations, imaging studies, and laboratory tests, to better understand these conditions and develop effective outcome measures for future clinical trials.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 4 weeks and older with childhood-onset neuromuscular disorders, their family members, and healthy volunteers.

Not a fit: Patients who are unable or unwilling to participate in examinations or do not have a parent or guardian to provide consent may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnosis and understanding of childhood nerve and muscle disorders, ultimately enhancing patient care and treatment options.

How similar studies have performed: Other studies focusing on the genetic and natural history of neuromuscular disorders have shown promise, indicating that this approach is both relevant and potentially impactful.

Eligibility criteria

* INCLUSION AND EXCLUSION CRITERIA:

Probands inclusion criteria Phase 1:

1. Aged 4 weeks and older
2. Documentation of a personal history of a childhood-onset, hereditary/familial, neurological disorder or later onset of a disease that more commonly has childhood onset. Acceptable documentation includes evaluation through any or all of the following evaluations done prior to enrollment.

   1. Medical history, including family history information
   2. Physical examination
   3. Muscle, nerve, or skin biopsy
   4. Magnetic resonance imaging (MRI)
   5. Electromyography (EMG)
   6. Nerve conduction study (NCS)
   7. Electroencephalogram (EEG)
   8. Muscle ultrasound
   9. Genetic, metabolic, or other laboratory testing such as increased serum Creatine Kinase (CK) and abnormal serum lactate/pyruvate ratio.

Exclusion criteria for probands Phase 1:

1. Individuals who are unable or unwilling to be examined
2. Minors who do not hve a parent or guardian able to provide informed consent
3. Adults seen offsite who are unable to provide their own consent

Probands inclusion criteria Phase 2:

1. Aged 4 weeks and older
2. Documentation of a defined childhood onset neuromuscular and neurogenetic disorders through phase 1 testing.

Exclusion criteria for probands Phase 2:

1. Individuals who are unable or unwilling to be examined.
2. Adults who are unable to provide their own consent and who have not previously appointed an individual with Durable Power of Attorney (DPA) or who are unable to appoint a DPA or guardian.
3. Minors who do not have a parent or guardian able to provide informed consent.
4. Adults seen offsite who are unable to provide their own consent.

Unaffected Family members - Inclusion Criteria:

1. Unaffected family members must be related by blood to a proband enrolled in the study. Biological relations may include first (parent or sibling), second (grandparents, aunts, uncles, half siblings) and third degree relatives (cousins).
2. Age 4 weeks and older.

Unaffected Family members - Exclusion Criteria:

1. Individuals whom are unable or unwilling to be examined.
2. Family members who are showing symptoms of the familial neurogenetic or neuromuscular condition (these may be enrolled as probands).
3. Neonates.
4. Adults who are unable to provide their own consent.

Healthy Volunteers - Inclusion Criteria:

1. Must be unaffected by a neurological condition.
2. Willing and able to comply with all protocol requirements and procedures, including MRI without sedation and without contrast.
3. Able to give informed assent and parent(s)/legal guardian to give informed consent in writing signed by the subject and/or parent(s)/legal guardian.

Healthy Volunteers - Exclusion Criteria:

1. Healthy volunteers who have metal objects in their body that are not MRI-safe. These include the following objects: 1) pacemakers or other implanted electrical devices; 2) brain stimulators; 3) some types of dental implants; 4) aneurysm clips (metal clips on the wall of a large artery); 5) metallic prostheses (including metal pins and rods, heart valves, and cochlear implants; 6) implanted delivery pump; 7) permanent eye liner; or 8) shrapnel fragments.
2. Healthy volunteers who have a fear of closed spaces.
3. Neonates.
4. Pregnant

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Carsten G Bonnemann, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
• Study coordinator: Sandra Donkervoort

Conditions Muscular Dystrophies; Muscle Myopathies; Hereditary Spastic Paraplegias; Inherited Neuropathies; Inherited Neuromuscular Conditions; Hereditary Myopathies; Neuropathology; Muscular Dystrophy