Genomic Profiling of Mitochondrial Disease - Imaging Analysis for Precise Mitochondrial Medicine

NCT ID: NCT05012358

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 9 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2024-01-22

Brief Summary

This study is an observational longitudinal study involving the use of MRIs and video recordings taken at home of patients completing basic tasks. Once consent is obtained, subjects will be asked to schedule an appointment with radiology to undergo the listed MRIs of the heart and/or muscle. Subjects will also be given instructions on how to use the video recording app on their personal devices, or study provided device. The subjects will be followed regularly over the course of two years, submitting video recordings of their movements and reporting to Mayo Clinic for MRIs as scheduled.

Detailed Description

Mitochondrial myopathy follows a slowly progressive disease course of gradual worsening of muscle weakness and fatigability. Progressive mitochondrial dysfunction is thought to result in structural muscle deterioration (eventually muscle fiber atrophy/necrosis) and underlie these symptoms. Therefore, the study hypothesis is that longitudinal imaging of muscle will capture mitochondrial (using muscle MRS) and structural (using muscle MRI) abnormalities to inform objectively disease progression by capturing structural and biochemical changes in muscle over time.

Conventional multivariate analysis tools such as partial least squares-discriminant analysis (PLS-DA) and principal component analysis (PCA) will be used to assess variables of importance in discrimination of 3 subgroups based on underlying molecular defect (mitochondrial DNA (mtDNA) mutations and deletions, and nuclear gene mutations (nDNA)).

This will be followed by implementation of Collaborative Laboratory Integrated Reports (CLIR) software, a multivariate pattern recognition software that generates post-analytical interpretive tools. This study proposes to quantitatively measure MRS analytes (i.e. lactate, adenosine triphosphate (ATP), etc.) and structural muscle changes by MRI (edema, fat content, etc.). The capability for interactive data analysis would be necessary because of the nature of mitochondrial myopathy (MM) progression. One of the functionalities of CLIR is the creation of post-analytical tools applicable to either diagnosis of one condition - single condition tool; or differential diagnosis between two conditions with overlapping phenotypes (mtDNA deletions, mtDNA mutations, nDNA mutations) - dual scatter plots. The advantages of CLIR are (1) integration of primary markers with all informative permutations of ratios/biomarkers. Ratios calculated between markers not directly related at the biochemical level are particularly helpful to correct for pre-analytical factors and potential analytical bias (2) adjusted for multiple covariates (age, sex) (3) generating individual plots of disease progression.

This study is an observational longitudinal study involving the use of MRIs and video recordings taken at home of patients completing basic tasks. Subjects will be approached at outpatient appointments, or via phone/mail. Once consent is obtained, subjects will be asked to schedule an appointment with radiology to undergo the listed MRIs of the heart and/or muscle. Subjects will also be given instructions on how to use the video recording app on their personal devices, or study provided device. The subjects will be followed regularly over the course of two years, submitting video recordings of their movements and reporting to Mayo Clinic for MRIs as scheduled. Patients may withdraw from the study at any time without repercussion.

Conditions

Mitochondrial Myopathies; Mitochondrial DNA Mutation; Mitochondrial Diseases; Chronic Progressive External Ophthalmoplegia With Myopathy; Kearns-Sayre Syndrome

Study Design

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

Study Groups

Observational Cohort

no intervention

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Confirmed or suspected primary mitochondrial disorder *Suspected mitochondrial disorder would mean that the patient meets clinical criteria and has either biopsy or biochemical testing that supports the diagnosis.

Exclusion Criteria

• Pregnant, breastfeeding
• Severe cardiac disease who are unable to undergo all the required testing
• Requiring anesthesia for MRIs
• Has severe claustrophobia
• Has implanted devices

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Casimir, LLC

UNKNOWN

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Ralitza Gavrilova

Associate Professor of Medical Genetics and Neurology, College of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ralitza Gavrilova, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

20-002721

Identifier Type: -

Identifier Source: org_study_id