Validation of Oxygen Nanosensor in Mitochondrial Myopathy

Study Overview
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Brief Summary
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Past mitochondrial disease treatment studies have been unsuccessful in determining treatment efficacy, and a major factor has been the lack of validated biomarkers in mitochondrial myopathy (MM). There is currently a growing number of potential new treatments to be tested through MM clinical intervention trials, which has created a pressing need for quantitative biomarkers that reliably reflect MM disease severity, progression, and therapeutic response. The purpose of the study is to measure the efficacy of an electrochemical oxygen nanosensor to measure in vivo mitochondrial function in human muscle tissue, and its ability to discriminate MM patients from healthy volunteers. The data and results from this nanosensor study may contribute to current and future research, including improved diagnostic and therapeutic approaches for patients with mitochondrial disease.

Detailed Description
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This is an investigational device clinical trial. MM cases and healthy volunteers will undergo nanosensor muscle oxygen measurement in exercised (dominant) forearm muscle during handgrip exercise. The same measurements will be repeated between 7 and 30 days later in the same forearm and at the same time of day for each participant to assess reproducibility. After placement of the nanosensor in the forearm under local anesthesia, the primary outcome measure is nanosensor-muscle oxygen levels. The secondary outcome measure is an assessment of pain.

Official Title
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The Development of Minimally Invasive Nanosensor Technology to Quantify Mitochondrial Function in Human Muscle

Conditions
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Mitochondrial Myopathies, Mitochondrial Diseases

Intervention / Treatment
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* Device: Nanosensor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Healthy Controls Males and females, between the ages of 18 and 65 years, inclusive Provide informed consent for study participation; able to understand and complete the protocol Able to ambulate independently Able to perform bicycle ergometry Inclusion Criteria for MM Cases Males and females, between the ages of 18 and 65 years, inclusive Provide informed consent for study participation; able to understand and complete the protocol Genetically-confirmed MM as defined by a diagnosis of primary mitochondrial disease (PMD) with predominant symptoms of myopathy as expressed by exercise intolerance and muscle weakness and fatigue. Previously enrolled (or will enroll) in Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) study #08-006177 (Falk, PI) or CHOP IRB #16-013364 (Zolkipli, PI) Able to ambulate independently Able to perform bicycle ergometry Exclusion Criteria for All Participants Subjects will be excluded if any of the following apply: Unable to provide informed consent and complete all study procedures, including ergometry Non-ambulatory or unable to ambulate independently Pregnant Within 1 month of a recent hospital admission due to acute illness Have severe cardiac disease as defined by an ejection fraction of less than 35% and New York Heart Association Functional Classification Class III; or severe pulmonary disease as defined by the need for supplemental O2 therapy or daytime ventilatory support Have a tracheostomy Have a known bleeding disorder and/or family history (first-degree relative) with a known bleeding disorder Daily intake of aspirin or any other anti-platelet therapy which cannot be temporarily discontinued for medical reasons a) Have known or suspected congenital or acquired immune deficiency; b) concurrent use of immunosuppressive drugs, including corticosteroids; c) past history of recurrent (more than 6 times per year) severe (required hospitalization) skin or soft tissue infections; d) history of infection or delayed wound healing after surgery or biopsy; e) known history of neutropenia with absolute neutrophil count less than 500/mm3 Undergo chronic steroid treatment as defined by daily oral intake (for more than 1 month) or have existing untreated endocrinopathies, such as hypothyroidism that caused acquired myopathy Prone to hypertrophic scars and keloids Have any other known inherited myopathy, such as Duchenne muscular dystrophy or congenital myopathy Known allergy to lidocaine Have a cognitive impairment that may prevent the ability to complete study procedures Unable to comply with the requirements of the study protocol and/or unsuitable for the study for any reason, in the opinion of the principal investigator Individuals from vulnerable populations (e.g., prisoners/detainees) Participants who are unable to speak and/or read English (as participants will be required to be proficient to complete study procedures)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Affected MM Cases<br>Key eligibility criteria for MM cases includes physically-capable adults (male and females, ages 18 to 65 years, inclusive) with genetically-confirmed MM with predominant symptoms of myopathy as expressed by exercise intolerance and muscle weakness and fatigue. | Device: Nanosensor<br>* The purpose of the study is to test a device called a nanosensor, which measures oxygen levels (a proxy of mitochondrial function) in muscle. The nanosensor has not been tested in humans nor has it been approved by the FDA. The study nanosensor measures 1.8 mm width x 6 mm length x 0.3 mm depth. Placement of the sterilized nanosensor involves a small incision for manual placement of the nanosensor in muscle forearm tissue.<br>|
| Other: Healthy Controls<br>Adult healthy volunteers will be individually matched with corresponding MM cases based on age, biological sex, and body mass index. | Device: Nanosensor<br>* The purpose of the study is to test a device called a nanosensor, which measures oxygen levels (a proxy of mitochondrial function) in muscle. The nanosensor has not been tested in humans nor has it been approved by the FDA. The study nanosensor measures 1.8 mm width x 6 mm length x 0.3 mm depth. Placement of the sterilized nanosensor involves a small incision for manual placement of the nanosensor in muscle forearm tissue.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nanosensor-muscle oxygen (Torr) levels | Nanosensor measured muscle O2 levels at baseline, during handgrip exercise and after exercise | 60 minutes for data collection at each 2 study visits, up to 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain and tolerability |  | At each 2 study visits, up to 6 months. |