Mitochondrial DiseasesNCT04734626
CrCest Study in Primary Mitochondrial Disease
An observational study of Mitochondrial Diseases, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
The purpose of this study is to perform a "muscle phenotyping" magnetic resonance imaging (MRI) assessment in patients receiving clinical care at the Children's Hospital of Philadelphia (CHOP) for mitochondrial disease that is either suspected (based on clinical presentation) or has a definite genetic diagnosis. Read more about this study
- Who is it for?
- Ages 7 to 75 years
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence
- How many people
- 230 participants
- Where
- 1 siteUnited States
- Study dates
- 25 May 2021to 31 Dec 2028
- 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 7 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population consists of suspected or definite mitochondrial disease patients who are receiving clinical care through the Mitochondrial Medicine Frontier Program
Who may be able to join
- Males and females, between the ages of 7 and 75, inclusive
- Suspected (based on clinical presentation) or definite genetic mitochondrial disease diagnosis (i.e., genetic mutations in the constituents of the mitochondrial respiratory chain and/or genetic mutations that are likely to affect mitochondrial function)
- Clinically eligible for an MRI of the lower leg. We are conducting clinical leg MRI scans of patients with definite mitochondrial disease for indications that include muscle weakness and muscle fatigue.
- Able to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
- Males and females, between the ages of 7 and 75 years, inclusive
- Able to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
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- Inclusion Criteria (Evaluable Healthy Controls and Cases for Data Analysis):
- To note, we will merge coded datasets from Institutional Review Board (IRB) #15-012445, IRB #16-013364, and IRB #08-006177 with data from this study as part of our data analysis plan.
- Complete and evaluable healthy control and cases from IRB #15-012445, IRB #16-013364, and IRB #08-006177
- Exclusion Criteria (Mitochondrial Disease Patients and Healthy Controls):
- In the investigator's opinion, inability to fully comply with research procedures
- Active 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)
- Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
- Any potentially interfering clinical MRI contrast agents, as reviewed with the radiology team
- 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 will be asked to perform a brief (< 2 minute) foot-pedal exercise. Investigators will ensure that total MRI scanning time (i.e., clinically indicated and study-specific scanning) does not exceed 120 minutes within a single day. Participants who do not possess the cognitive and/or physical abilities to perform these procedures will not be included.
Who cannot join
- Any history or genetic confirmation of mitochondrial disease
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
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Magnetic Resonance Imaging (MRI) Muscle Phenotyping in Mitochondrial Disease
The purpose of this study is to perform a "muscle phenotyping" magnetic resonance imaging (MRI) assessment in patients receiving clinical care at the Children's Hospital of Philadelphia (CHOP) for mitochondrial disease that is either suspected (based on clinical presentation) or has a definite genetic diagnosis. The MRI assessment quantifies skeletal muscle oxidative phosphorylation (OXPHOS) capacity.
Investigators hope that this study will contribute to our current knowledge of mitochondrial diseases and this study will help create a new diagnostic tool for use in both clinical care and in clinical trials.
Read the detailed description
This research study visit will occur on the same day as the participants clinically scheduled MRI. The clinically indicated and study-specific scanning time will not exceed 120 minutes.
During the study visits:
- A study team member will review inclusion and exclusion criteria with the participant
- A study team member will review medical history review with the participant
- A safety assessment will occur prior to study procedures
- Study MRI scan
- During which the participant will use an MRI-safe machine to stimulate exercise, similar to pressing a gas pedal
If eligible participants return to CHOP for future clinical imaging, we will also request a study-specific MRI assessment.
- Conditions
- Mitochondrial Diseases
- Being tested
- Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging SequenceDiagnostic test
CrCEST be used to assess creatine distribution and concentrations in muscle (lower extremity), both at rest and after recovery from a brief foot-pedal depression exercise
| Study group | Role | What they receive |
|---|---|---|
| Mitochondrial Disease | Individuals with suspected (based on clinical presentation) or definite genetic mitochondrial disease Receives: Diagnostic Test: Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence | |
| Healthy Controls/Volunteers | Individuals with no history of suspected (based on clinical presentation) or definite genetic mitochondrial disease Receives: Diagnostic Test: Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-exercise CrCEST recovery time (seconds)
The time it takes after the exercise occurs to recover CrCEST
Measured: During the MRI
Secondary outcomes (3)
Resting CrCEST
Amount of CrCEST prior to exercise
Measured: During the MRI
Muscle Lipid Content
Includes both Intramyocellular lipid (IMCL) and extramyocellular lipids (EMCL) content, both expressed in arbitrary units relative to water signal and relative to creatine
Measured: During the MRI
Fat-fraction
n-point Dixon, expressed as a percentage of the total area
Measured: During the MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start25 May 2021
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies 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
- Prospective
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Zarazuela Zolkipli Cunningham, MBChB MRCP, Principal investigator, Children's Hospital of Phiadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734626
- Sponsor's protocol ID
- 19-016520
- Other IDs
- 1R01AR083552-01A1
- Status last verified
- Jan 2026
- First submitted
- 25 Jan 2021
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Imaging (MRI) Muscle Phenotyping in Mitochondrial Disease
- ClinicalTrials.gov ID
- NCT04734626
- Acronym / sponsor ID
- 19-016520
- Conditions
- Mitochondrial Diseases
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 25 May 2021 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 2 Feb 2021 (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.
The purpose of this study is to perform a "muscle phenotyping" magnetic resonance imaging (MRI) assessment in patients receiving clinical care at the Children's Hospital of Philadelphia (CHOP) for mitochondrial disease that is either suspected (based on clinical presentation) or has a definite genetic diagnosis. The MRI assessment quantifies skeletal muscle oxidative phosphorylation (OXPHOS) capacity.
Investigators hope that this study will contribute to our current knowledge of mitochondrial diseases and this study will help create a new diagnostic tool for use in both clinical care and in clinical trials.
Detailed description
This research study visit will occur on the same day as the participants clinically scheduled MRI. The clinically indicated and study-specific scanning time will not exceed 120 minutes.
During the study visits:
- A study team member will review inclusion and exclusion criteria with the participant
- A study team member will review medical history review with the participant
- A safety assessment will occur prior to study procedures
- Study MRI scan
- During which the participant will use an MRI-safe machine to stimulate exercise, similar to pressing a gas pedal
If eligible participants return to CHOP for future clinical imaging, we will also request a study-specific MRI assessment.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitochondrial Disease | – | Diagnostic Test: Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging SequenceIndividuals with suspected (based on clinical presentation) or definite genetic mitochondrial disease |
| Healthy Controls/Volunteers | – | Diagnostic Test: Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging SequenceIndividuals with no history of suspected (based on clinical presentation) or definite genetic mitochondrial disease |
Who may qualify
- Ages
- 7 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population consists of suspected or definite mitochondrial disease patients who are receiving clinical care through the Mitochondrial Medicine Frontier Program
Key inclusion criteria (21 listed)
- Males and females, between the ages of 7 and 75, inclusive
- Suspected (based on clinical presentation) or definite genetic mitochondrial disease diagnosis (i.e., genetic mutations in the constituents of the mitochondrial respiratory chain and/or genetic mutations that are likely to affect mitochondrial function)
- Clinically eligible for an MRI of the lower leg. We are conducting clinical leg MRI scans of patients with definite mitochondrial disease for indications that include muscle weakness and muscle fatigue.
- Able to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
- Males and females, between the ages of 7 and 75 years, inclusive
Key exclusion criteria (1 listed)
- Any history or genetic confirmation of mitochondrial disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging SequenceCrCEST be used to assess creatine distribution and concentrations in muscle (lower extremity), both at rest and after recovery from a brief foot-pedal depression exercise | Diagnostic test | Healthy Controls/Volunteers, Mitochondrial Disease |
Primary outcome
Post-exercise CrCEST recovery time (seconds)
Time frame: During the MRI
The time it takes after the exercise occurs to recover CrCEST
3 secondary outcomes
Resting CrCEST
Time frame: During the MRI
Muscle Lipid Content
Time frame: During the MRI
Fat-fraction
Time frame: During the MRI
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 14 Jan 2026.
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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.
Zarazuela Zolkipli Cunningham, MBChB MRCP principal investigator
Children's Hospital of Phiadelphia
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 Mitochondrial Diseases, 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 21 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 14 Jan 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-exercise CrCEST recovery time (seconds) (time frame: During the MRI). 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 14 Jan 2026.