CrCest Study in Primary Mitochondrial Disease

NCT ID: NCT04734626

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 230 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-25
• Study Completion Date: 2028-12-31

Brief 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. 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.

Conditions

Mitochondrial Diseases

Study Design

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

Study Groups

Mitochondrial Disease

Individuals with suspected (based on clinical presentation) or definite genetic mitochondrial disease

Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence

Intervention Type: DIAGNOSTIC_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

Healthy Controls/Volunteers

Individuals with no history of suspected (based on clinical presentation) or definite genetic mitochondrial disease

Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence

Intervention Type: DIAGNOSTIC_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

Interventions

Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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.

• Any history or genetic confirmation of mitochondrial disease

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zarazuela Zolkipli Cunningham, MBChB MRCP

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Phiadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

1R01AR083552-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-016520

Identifier Type: -

Identifier Source: org_study_id