Validation of Oxygen Nanosensor in Mitochondrial Myopathy
Primary Purpose
Mitochondrial Myopathies, Mitochondrial Diseases
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Nanosensor
Sponsored by
About this trial
This is an interventional diagnostic trial for Mitochondrial Myopathies
Eligibility Criteria
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)
Sites / Locations
- The Children's Hospital of PhiladelphiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Affected MM Cases
Healthy Controls
Arm Description
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.
Adult healthy volunteers will be individually matched with corresponding MM cases based on age, biological sex, and body mass index.
Outcomes
Primary Outcome Measures
Nanosensor-muscle oxygen (Torr) levels
Nanosensor measured muscle O2 levels at baseline, during handgrip exercise and after exercise
Secondary Outcome Measures
Pain and tolerability
Full Information
NCT ID
NCT04086329
First Posted
September 6, 2019
Last Updated
February 20, 2023
Sponsor
Children's Hospital of Philadelphia
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT04086329
Brief Title
Validation of Oxygen Nanosensor in Mitochondrial Myopathy
Official Title
The Development of Minimally Invasive Nanosensor Technology to Quantify Mitochondrial Function in Human Muscle
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 17, 2023 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
National Institutes of Health (NIH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Myopathies, Mitochondrial Diseases
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Affected MM Cases
Arm Type
Other
Arm Description
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.
Arm Title
Healthy Controls
Arm Type
Other
Arm Description
Adult healthy volunteers will be individually matched with corresponding MM cases based on age, biological sex, and body mass index.
Intervention Type
Device
Intervention Name(s)
Nanosensor
Intervention Description
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.
Primary Outcome Measure Information:
Title
Nanosensor-muscle oxygen (Torr) levels
Description
Nanosensor measured muscle O2 levels at baseline, during handgrip exercise and after exercise
Time Frame
60 minutes for data collection at each 2 study visits, up to 6 months.
Secondary Outcome Measure Information:
Title
Pain and tolerability
Time Frame
At each 2 study visits, up to 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zarazuela Zolkipli-Cunningham
Phone
(267) 331-1365
Email
zolkipliz@chop.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Nguyen
Phone
(267) 426-1986
Email
nguyens2@chop.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zarazuela Zolkipli-Cunningham
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zarazuela Zolkipli-Cunningham, MBChB, MRCP
Email
zolkipliz@chop.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Validation of Oxygen Nanosensor in Mitochondrial Myopathy
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