Nanosensor for Mitochondrial Myopathy

Overseen By Daniel McGinn, MS, LCGC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital of Philadelphia

Must not be taking: Aspirin, Immunosuppressants, Corticosteroids

Disqualifiers: Severe cardiac disease, Severe pulmonary disease, Bleeding disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: up to 4 hours

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new nanosensor (a diagnostic device) can effectively measure mitochondrial function in muscle tissue, potentially aiding in the diagnosis and treatment of mitochondrial myopathy, a condition causing muscle weakness and fatigue. The study compares results from individuals with this condition to those from healthy volunteers. It seeks participants diagnosed with mitochondrial myopathy who experience symptoms such as exercise intolerance and muscle weakness. Participants must be able to walk and perform activities like cycling. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on daily aspirin or anti-platelet therapy that can't be stopped temporarily, or if you are on chronic steroid treatment.

What prior data suggests that this nanosensor is safe for measuring mitochondrial function?

Research shows that specific safety information for the nanosensor treatment in humans is not yet available. This trial, in its early stages, primarily focuses on assessing safety and identifying any side effects. As a result, any known risks are likely minimal at this point.

Before human testing, researchers studied the nanosensor in labs, where it demonstrated the ability to measure oxygen levels in muscle tissues. These lab studies are crucial for predicting how the treatment might perform in people.

In this early phase study, safety remains a top priority. Researchers closely monitor participants for any issues. Although specific safety data is not yet available, the trial is designed to quickly identify and address any problems that may arise. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the nanosensor for mitochondrial myopathy because it offers a groundbreaking way to monitor the disease. Unlike traditional treatments that focus on managing symptoms like muscle weakness and fatigue, this nanosensor aims to detect changes at the cellular level, providing real-time insights into mitochondrial function. This could lead to more precise and personalized treatment plans, potentially improving outcomes for patients with mitochondrial myopathy.

What evidence suggests that this nanosensor is effective for mitochondrial myopathy?

Research shows that a new tiny sensor could offer a novel method to measure muscle function. Early studies have examined its ability to detect changes in oxygen levels, crucial for understanding mitochondrial myopathy, a condition affecting cellular energy production. In preclinical tests, the sensor successfully measured oxygen levels in muscles both at rest and post-exercise. Although the sensor is not a treatment, it could help monitor the effectiveness of potential treatments. This advancement might lead to improved diagnosis and treatment of mitochondrial diseases in the future. ^{1 2 6 7 8}

Who Is on the Research Team?

Zarazuela Zolkipli-Cunningham, MBChB, MRCP

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for healthy adults and those with genetically-confirmed mitochondrial myopathy (MM), aged 18 to 65, who can consent, understand the protocol, walk on their own, and do bicycle ergometry. Excluded are non-ambulatory individuals, pregnant women, immune-compromised persons or those on immunosuppressive drugs, people with severe skin infections or neutropenia, chronic steroid users, certain myopathy cases other than MM.

Inclusion Criteria

I am 18-65 with confirmed mitochondrial myopathy, can walk, and can do a bike test.

Exclusion Criteria

I cannot walk on my own.

Pregnant

Immune deficiency, use of immunosuppressive drugs, history of severe skin or soft tissue infections, history of neutropenia, chronic steroid treatment, hypertrophic scars and keloids, known inherited myopathy, allergy to lidocaine, cognitive impairment, inability to comply with study protocol, individuals from vulnerable populations, inability to speak and/or read English proficiently, employed by the U.S. Department of Defense

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 40 days

Treatment

Nanosensor muscle oxygen measurement in exercised forearm muscle during handgrip exercise

up to 4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including self-reported pain and fatigue assessments

up to 40 days

What Are the Treatments Tested in This Trial?

Interventions

• Nanosensor

Trial Overview The study tests an electrochemical oxygen nanosensor's ability to measure mitochondrial function in human muscle tissue of MM patients versus healthy volunteers. It aims to establish a reliable biomarker for disease severity and treatment response in mitochondrial diseases.

How Is the Trial Designed?

Group I: Affected Mitochondrial Myopathy (MM) Cases Experimental Treatment 1 Intervention

Key eligibility criteria for Mitochondrial Myopathy (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.

Group II: Healthy Controls Active Control 1 Intervention

Adult healthy volunteers will be individually matched with corresponding Mitochondrial Myopathy cases based on age, biological sex, and body mass index.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a phase-3 clinical trial involving 218 participants with primary mitochondrial myopathies, elamipretide did not show significant improvement in walking distance or fatigue levels compared to placebo after 24 weeks.

Despite the lack of efficacy in improving primary endpoints, elamipretide was well-tolerated, with most adverse events being mild to moderate, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Karaa, A., Bertini, E., Carelli, V., et al.[2023]

The new lab-on-a-chip device for mitochondrial functional assays requires significantly less mitochondrial protein—up to 1000 times less—than traditional methods, making it more accessible for research.

This second-generation system shows improved sensitivity and durability, allowing for better detection of changes in mitochondrial membrane potential, which is crucial for studying degenerative diseases and aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wafer-scale mitochondrial membrane potential assays. Lim, TS., Davila, A., Zand, K., et al.[2021]

Patients with mitochondrial myopathies (MM) commonly experience exercise intolerance, characterized by reduced maximal oxygen consumption (VO2max) and increased carbon dioxide production (VCO2), which can be assessed through standard exercise testing protocols.

Aerobic exercise testing, particularly with measurements of oxygen consumption, is effective for diagnosing and monitoring MM, showing good sensitivity (0.63-0.75) and specificity (0.70-0.90), and can be enhanced with additional techniques like near-infrared spectroscopy and magnetic resonance spectroscopy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise testing as a diagnostic entity in mitochondrial myopathies. Tarnopolsky, M.[2005]

In a study of 118 patients with primary mitochondrial myopathy (PMM), various functional tests and biomarkers were found to significantly differ from healthy controls, indicating their potential as reliable outcome measures for monitoring PMM.

Functional measures correlated with patients' reported fatigue and pain, suggesting that these assessments can help evaluate the impact of PMM on daily life and may be useful in clinical trials to track treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary mitochondrial myopathy: Clinical features and outcome measures in 118 cases from Italy. Montano, V., Gruosso, F., Carelli, V., et al.[2022]

A study of 27,140 reported cases of rhabdomyolysis identified 14 drugs, including fenofibrate and risperidone, that are linked to mitochondrial toxicity, suggesting a common mechanism for drug-induced muscle damage.

Using murine L6 cells and human skeletal muscle-derived cells, researchers confirmed that these drugs cause significant mitochondrial dysfunction, indicating that the L6 model could be a useful and cost-effective tool for screening potential myotoxic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing In Vitro Models to Define the Role of Direct Mitochondrial Toxicity in Frequently Reported Drug-Induced Rhabdomyolysis. Bin Dayel, FF., Alfirevic, A., Chadwick, AE.[2023]

In a study involving six patients with mitochondrial myopathy, bezafibrate was found to be safe with no significant adverse effects, and it improved mitochondrial function by reducing complex IV-immunodeficient muscle fibers and enhancing cardiac function over 12 weeks.

However, the treatment also led to increased serum biomarkers associated with mitochondrial disease and changes in fatty acid and amino acid metabolism, suggesting potential long-term risks that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic effects of bezafibrate in mitochondrial disease. Steele, H., Gomez-Duran, A., Pyle, A., et al.[2022]

In a study on D2.mdx mice with Duchenne muscular dystrophy, the compound Olesoxime was found to preserve mitochondrial creatine sensitivity in limb and respiratory muscles during early stages of the disease, suggesting it may help mitigate mitochondrial stress.

Olesoxime treatment led to reduced muscle damage (as indicated by lower serum creatine kinase levels) and improved muscle quality, including better recovery of diaphragm force and maintenance of lean muscle volume, although it did not significantly affect grip strength or voluntary activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondrial creatine sensitivity is lost in the D2.mdx model of Duchenne muscular dystrophy and rescued by the mitochondrial-enhancing compound Olesoxime. Bellissimo, CA., Delfinis, LJ., Hughes, MC., et al.[2023]

In a study of 10 patients with mitochondrial myopathies who underwent 8 weeks of moderate-intensity aerobic training, their estimated aerobic capacity increased by 30%, indicating significant improvement in physical fitness.

The training also led to a 30% reduction in blood lactate levels and over 60% improvement in muscle recovery after exercise, suggesting that aerobic training can enhance both biochemical and functional measures in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of aerobic training in patients with mitochondrial myopathies. Taivassalo, T., De Stefano, N., Argov, Z., et al.[2019]

Serum FGF21 (S-FGF21) levels are significantly elevated in patients with primary mitochondrial myopathy, particularly in those with mitochondrial translation defects or mtDNA deletions, making it a specific biomarker for these conditions.

While S-FGF21 shows high specificity (89.3%) for diagnosing mitochondrial myopathy, it does not rule out other types of mitochondrial defects, highlighting the need for comprehensive diagnostic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders. Lehtonen, JM., Forsström, S., Bottani, E., et al.[2022]

This study successfully demonstrated that mitochondria-based piezosensors can detect ion fluxes through mitochondrial K+-ion channels, which could be useful for drug development targeting these channels.

The research showed that these sensors can respond to changes in ion dynamics and mitochondrial behavior, even when using a polypyrrole binding film, indicating their potential for studying drug effects at very low concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria-based biosensors with piezometric and RELS transduction for potassium uptake and release investigations. Stobiecka, M., Jakiela, S., Chalupa, A., et al.[2017]

Oligomycin-inhibited mitochondria-modified electrodes can effectively sense nitroaromatics by decoupling the inhibition of pyruvate metabolism, showcasing a novel method for detecting these compounds.

These electrodes can function as both traditional electrochemical sensors and self-powered sensors in a pyruvate/air biofuel cell, indicating their versatility in practical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitroaromatic actuation of mitochondrial bioelectrocatalysis for self-powered explosive sensors. Germain, MN., Arechederra, RL., Minteer, SD.[2009]

The French network of mitochondrial disease diagnostic centers identified significant variability in respiratory chain spectrophotometric assay results due to differing protocols, which can complicate comparisons between centers.

To address this issue, the network standardized and optimized testing protocols, leading to improved consistency in diagnostic results across multiple centers, with experimental data and protocols made freely accessible online.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis. Medja, F., Allouche, S., Frachon, P., et al.[2019]

Citations

1. trialx.com trialx.com/clinical-trials/listings/229866/validation-of-oxygen-nanosensor-in-mitochondrial-myopathy/?&geo_lat=40.0&geo_lng=-75.276&radius=10&place=Wynnewood&user_country=United%20States

Validation of Oxygen Nanosensor in Mitochondrial Myopathy The purpose of the study is to measure the efficacy of an electrochemical oxygen nanosensor to measure in vivo mitochondrial function in human ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/partner/umdf/trial/574758

Validation of Nanosensor Oxygen Measurement 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, ...

3. withpower.com withpower.com/trial/phase-1-mitochondrial-myopathies-2025-c0767

Nanosensor for Mitochondrial Myopathy In a phase-3 clinical trial involving 218 participants with primary mitochondrial myopathies, elamipretide did not show significant improvement in walking ...

4. neurology.org neurology.org/doi/10.1212/WNL.92.15_supplement.S32.009

Development of a minimally invasive muscle O2 ... We report results of a pre-clinical study to test the safety and efficacy of a prototype O 2 sensor to quantify muscle O 2 levels at rest and after exercise in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12301291/

Therapies for Mitochondrial Disease: Past, Present, and Future A phase I/II clinical trial to evaluate the safety and efficacy of MAT in children with Pearson syndrome has been completed with results yet to ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/553796

Validation of Oxygen Nanosensor in Mitochondrial Myopathy The purpose of the study is to measure the efficacy of an electrochemical oxygen nanosensor to measure in vivo mitochondrial function in human ...

7. withpower.com withpower.com/trial/phase-mitochondrial-diseases-8-2021-0dd80

Oxygen Nanosensor for Mitochondrial Myopathy However, specific safety data for humans is not provided in the available studies. ... What data supports the effectiveness of the treatment Oxygen Nanosensor for ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0048969719349861

Mitochondrial toxicity of nanomaterials In this review, we have provided an overview of the multiple subcellular, cellular and in vivo toxic effects of NMs on mitochondria.