Neurometabolic Profile of Individuals With Primary Mitochondrial Disease

NCT ID: NCT06890520

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-25
• Study Completion Date: 2026-01-01

Brief Summary

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.

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.

Conditions

Primary Mitochondrial Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Genetically Confirmed Primary Mitochondrial Disease

Individuals with Genetically Confirmed Primary Mitochondrial Disease

No interventions assigned to this group

Healthy Controls

Individuals who have no history of Primary Mitochondrial Disease

No interventions assigned to this group

Eligibility Criteria

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

• 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.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zarazuela Zolkipli-Cunningham

Role: CONTACT

mmfpclinicalresearch@chop.edu

(267) 426-4961

Facility Contacts

Zarazuela Zolkipli-Cunningham

Role: primary

mmfpclinicalresearch@chop.edu

267-426-4961

Other Identifiers

24-022407

Identifier Type: -

Identifier Source: org_study_id