Electrical Impedance Myography: Natural History Studies inNeuromuscular Disorders and Healthy Volunteers

Title: Electrical Impedance Myography: Natural History Studies in Neuromuscular Disorders and Healthy Volunteers

Study Description: This is a natural history study examining the utility of electrical impedance myography (EIM) device in the evaluation of neuromuscular disorders. This is a novel device so the initial step was to establish reproducibility of the data and expected normative values using the EIM device on healthy volunteers. In neuromuscular disorders, the EIM device will be used to understand the results in different types of neuromuscular disorders. A subset of subjects with neuromuscular disorders are studied serially as preliminary evaluation of its utility as a biomarker in clinical studies. The protocol includes both adult and pediatric subjects.

Objectives:

Primary objective: For subjects with neuromuscular disease, we aim to understand if EIM has utility in differentiating neuromuscular disorders in adult and pediatric subjects. Also, to perform preliminary serial studies to understand the EIM device potential use as biomarker in clinical studies.

For healthy volunteers, the primary objective is reproducibility of results and the range of normative values in adult and pediatric subjects.

Secondary objectives: The three parameters, phase, reactance, resistance will be followed serially as measures of change in pediatric population.

As exploratory outcome measures, we will explore correlations between EIM and ultrasound and other electrodiagnostic methods.

Endpoints:

Primary endpoint:

For healthy volunteers, intra and interrater reliability will be evaluated to determine the utility of EIM as a reproducible biomarker. Normative values will be developed using a range of ages, mixed gender, and race to be used as a basis of comparison with subjects with neuromuscular disorders.

For subjects with neuromuscular disorders, patterns of phase, resistance and reactance in different types of neuromuscular disorders will be evaluated and examined for patterns specific to type of neuromuscular disorder.

Secondary endpoint:

The three parameters, phase, reactance, resistance will be followed serially as measures of change. This will be in evaluated small groups of neuromuscular disorders that are referred to this protocol. A cohort of pediatric healthy volunteers will be followed for two years for comparative data with pediatric subjects with neuromuscular disorders.

Exploratory endpoint:

The EIM phase, muscle ultrasound and possibly MUNIX will be compared in healthy volunteers.

Study Population: 275

(150) Patients with neuromuscular disease, over age 2

(125) Healthy Volunteers; 90 adults age 18 and above; 35 children age 7 to 17.

Description of Sites/Facilities Enrolling Participants:All studies will be performed in the NIH Clinical Center. The majority of the studies will occur in the EMG Lab. The EMG Lab is an AANEM-accredited EMG lab to perform diagnostic electrodiagnostic studies with experience in both pediatric and adult populations. At the convenience for the subject, the EIM study can be performed in other parts of the NIH Clinical Center.

Study Duration: It is estimated that the duration of the study will be 10 years. With closure in 2023.

Participant Duration: For the healthy volunteers, we will be evaluating EIM along with possible ultrasound and electrodiagnostic methods. A single session will be 3 hours or less. Repeat studies may be performed to establish reproducibility after the initial studies are completed. For subjects with neuromuscular disease, the studies will be conducted in a single outpatient session of 3 hours or less, unless a follow-up study is requested by the primary team. For children, the session will be 2 hours or less.

• INCLUSION CRITERIA:

HEALTHY VOLUNTEERS-ADULTS

• Healthy adults, male or female, aged 18 years old or older,
• In good general health as evidenced by medical history
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability of subject to understand and the willingness to sign a written informed consent document.

HEALTHY VOLUNTEERS-PEDIATRIC

• Healthy children, male or female, age 7-18,
• In good general health as evidenced by medical history
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Ability of subject or Legally Authorized Representative (LAR)) to understand and the willingness to sign a written informed consent document.

SUBJECTS WITH NEUROMUSCULAR DISEASE

Adult and pediatric, male or female, patients with a neuromuscular disorder are eligible even if the exact etiology of the disorder is unknown at the time of enrollment into this study. This will include neuropathy, myopathy and motor neuron disorders. It is expected that the subjects are undergoing appropriate standard diagnostic and genetic work-up outside of this protocol that will later clarify the specific etiology of the disorder. Movement disorder will also be included because of the prior research done on dystonia and EIM.

Inclusion criteria

• Suspected motor neuron disease or
• Suspected myopathy or
• Suspected neuropathy or
• Suspected movement disorders that impair intracortical processes
• Age of 2 years or older
• Ability of subject to sign a written informed consent document.

NIH EMPLOYEES:

NIH employees and staff may participate, however EMG Section, OCD, NINDS, employees may not participate.

Exclusion criteria

HEALTHY VOLUNTEERS-ADULTS

• Medical conditions that require medications that affects the physiological measures being tested. Some conditions that may be excluded are diabetes, kidney and liver disease.
• History of stroke, muscle disorders, peripheral neuropathy or spine surgery

HEALTHY VOLUNTEERS-PEDIATRIC

• Medical conditions that require medications that affects the physiological measures being tested. Some conditions that may be excluded are diabetes, kidney and liver disease.
• History of stroke, muscle disorders, peripheral neuropathy or spine surgery

SUBJECTS WITH NEUROMUSCULAR DISEASE:

No clinical evidence of a neuromuscular disorder on clinical evaluation.