Neurometabolic Profile of Individuals With Primary Mitochondrial Disease

February 4, 2026 updated by: Children's Hospital of Philadelphia
Primary Mitochondrial Disease (PMD) is a genetic neurometabolic disorder, leading to central nervous system degeneration and increased risk of early mortality. There is a strong link between the pathophysiology of mitochondrial disease and biomarkers related to the biochemistry of redox imbalance, involving the levels of glutathione. Investigators will use Magnetic Resonance Imaging and Spectroscopy to non-invasively measure glutathione and other chemicals in the brain to identify redox imbalance in patients with PMD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Primary Mitochondrial Disease (PMD) is a genetic neurometabolic disorder, leading to the degeneration of the central nervous system (CNS) and increased risk of early mortality. PMD can be caused by mutations in several genes in the mitochondrial DNA as well as nuclear DNA. Although a rare disease, PMD can significantly impact quality of life, increasing healthcare costs and caregiver burden. There is a lack of non-invasive, validated, and objective markers of mitochondrial function. However, there is a strong link between the pathophysiology of mitochondrial disease and biomarkers related to the biochemistry of redox imbalance, involving the levels of glutathione (GSH). Redox imbalance can also result in the overgeneration of radicals, causing neuronal damage. With the advancement in magnetic resonance techniques, the investigators can measure the levels of GSH and other neurochemicals non-invasively in the brain. Investigators in this proposal will use Magnetic Resonance Spectroscopy and Imaging (MRS and MRI) to measure brain chemicals, structure, and function.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • The Children's Hospital of Philadelphia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

This is an observational study among two study population groups: genetically confirmed PMD patients and healthy volunteers.

Description

Inclusion Criteria:

  • Must be between 8 and 75 years, inclusive
  • Genetically confirmed primary mitochondrial disease
  • Receiving standard-of-care treatment including mitochondrial supplements that may include N-acetylcysteine (NAC), a precursor of glutathione

Inclusion Criteria for Healthy Controls:

  • Must be between 8 and 75 years, inclusive

Exclusion Criteria:

  • MRI contraindications
  • In the investigator's opinion, inability to fully comply with research procedures
  • Active self-reported alcohol and/or substance abuse, including tobacco-use
  • A pacemaker; any metal-based medical or non-medical devices/implants; any non-removable metal-based object (e.g., body piercings, jewelry, etc.) that cannot be cleared through radiologic evaluation
  • Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
  • Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
  • Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
  • At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
  • Any female participant with childbearing potential who is knowingly pregnant or suspects that she is pregnant will be removed from the study. (Although there are no known risks of MRI on pregnant females or fetuses, there is a possibility of yet undiscovered pregnancy-related risks. Since there is no direct benefit from participating in this protocol for pregnant females, they will be excluded to ensure their long-term safety and that of their unborn fetus.)
  • To note, for this protocol, participants are instructed to lie still in the MRI scanner; there is no contrast or sedation. Participants who do not possess the cognitive and / or physical abilities to perform these procedures will not be included.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Genetically Confirmed Primary Mitochondrial Disease
Individuals with Genetically Confirmed Primary Mitochondrial Disease
Healthy Controls
Individuals who have no history of Primary Mitochondrial Disease

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assess group differences in brain chemical levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time Frame: Approximately 1 day
Metabolite concentrations from H Magnetic Resonance Spectroscopy (MRS) will be processed in Osprey followed by linear combination modelling of MRS spectra. Water-scaled metabolite estimates will be calculated and corrected for tissue composition and relaxation effects to generate metabolite concentrations.
Approximately 1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Plasma glutathione levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time Frame: Approximately 1 day
Analyze and report plasma glutathione levels (µM) in affected cases versus healthy controls. Glutathione is an antioxidant that protects cells from oxidative stress and detoxification. Differences between the two groups is anticipated.
Approximately 1 day
Change in Corticol Thickness in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time Frame: Approximately 1 day
Morphometric analyses and reporting of cortical thickness, surface area, and volume in affected cases versus healthy controls. Reporting cortical thickness involves using structural magnetic resonance imaging (MRI) to measure the width of the gray matter of the cortex, typically in millimeters, and analyzing regional variations to asses brain structure and function.
Approximately 1 day
Change in Cerebral Blood Flow in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time Frame: Approximately 1 day
Cerebral blood flow imaging (using spin labeling or similar), analyses, and reporting in affected cases versus healthy controls. Studying blood flow in the brain can assess for cerebrovascular disease.
Approximately 1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Philadelphia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 25, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 19, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 24-022407

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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