Primary Mitochondrial DiseaseNCT06890520
Neurometabolic Profile of Individuals With Primary Mitochondrial Disease
An observational study of Primary Mitochondrial Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Mitochondrial Disease
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2025to 1 Jan 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 75 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: This is an observational study among two study population groups: genetically confirmed PMD patients and healthy volunteers.
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Zarazuela Zolkipli-Cunningham, 267-426-4961, mmfpclinicalresearch@chop.edu
About this study
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.
Read the 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Assess group differences in brain chemical levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
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.
Measured: Approximately 1 day
Secondary outcomes (3)
Change in Plasma glutathione levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
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.
Measured: Approximately 1 day
Change in Corticol Thickness in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
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.
Measured: Approximately 1 day
Change in Cerebral Blood Flow in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
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.
Measured: Approximately 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start25 Feb 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Mitochondrial DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06890520
- Sponsor's protocol ID
- 24-022407
- Status last verified
- Feb 2026
- First submitted
- 19 Feb 2025
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurometabolic Profile of Individuals With Primary Mitochondrial Disease
- ClinicalTrials.gov ID
- NCT06890520
- Acronym / sponsor ID
- 24-022407
- Conditions
- Primary Mitochondrial Disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- 25 Feb 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 24 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Genetically Confirmed Primary Mitochondrial Disease | – | –Individuals with Genetically Confirmed Primary Mitochondrial Disease |
| Healthy Controls | – | –Individuals who have no history of Primary Mitochondrial Disease |
Who may qualify
- Ages
- 8 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This is an observational study among two study population groups: genetically confirmed PMD patients and healthy volunteers.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
3 secondary outcomes
Change in Plasma glutathione levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time frame: 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
Change in Cerebral Blood Flow in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Time frame: Approximately 1 day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Primary Mitochondrial Disease
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 3
KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
Mitochondrial Diseases, Maternally Inherited Diabetes and Deafness (MIDD)
Not yet recruitingPhase 1/2
A Basket Clinical Study to Assess Glycerol Tributyrate in Patients With Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like Episodes (MELAS) or Leber's Hereditary Optic Neuropathy-Plus (LHON-Plus)
MELAS Syndrome, Lebers Hereditory Optic Neuropathy With Extra Ocular Symptoms (LHON-Plus)
Not yet recruitingObservational study
The Precision Mito- Mito Map COMPASS Study
Mitochondrial Diseases, Myalgic Encephalomyelitis Chronic Fatigue Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Mitochondrial Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zarazuela Zolkipli-Cunningham ((267) 426-4961, mmfpclinicalresearch@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.