CrCest Study in Primary Mitochondrial Disease

NCT04734626 | Enrolling By Invitation

• 2 other identifiers: 19-0165201R01AR083552-01A1
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 1

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.

Conditions

Mitochondrial Diseases

Outcome Measures

Primary Outcomes (1)

• Post-exercise CrCEST recovery time (seconds)

  The time it takes after the exercise occurs to recover CrCEST

  During the MRI

Secondary Outcomes (3)

• Resting CrCEST

  During the MRI

• Muscle Lipid Content

  During the MRI

• Fat-fraction

  During the MRI

Study Arms (2)

Mitochondrial Disease

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

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

Diagnostic Test: Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence

Interventions

Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging Sequence 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; Mitochondrial Disease

Eligibility Criteria

• Age: 7 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of suspected or definite mitochondrial disease patients who are receiving clinical care through the Mitochondrial Medicine Frontier Program

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• Children's Hospital of Philadelphia: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Zarazuela Zolkipli Cunningham, MBChB MRCP

  Children's Hospital of Phiadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: February 2, 2021
• Study Start: May 25, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (1)