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

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ClinicalTrials.gov Identifier: NCT05012358
Recruitment Status : Recruiting
First Posted : August 19, 2021
Last Update Posted : December 30, 2021
Sponsor:
Collaborators:
Casimir, LLC
Astellas Pharma Inc
Information provided by (Responsible Party):
Ralitza Gavrilova, Mayo Clinic

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.

Condition or disease
Mitochondrial Myopathies Mitochondrial DNA Mutation Mitochondrial Diseases Chronic Progressive External Ophthalmoplegia With Myopathy Kearns-Sayre Syndrome

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.

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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genomic Profiling of Mitochondrial Disease - Imaging Analysis for Precise Mitochondrial
Estimated Study Start Date : January 3, 2022
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : December 30, 2023


Group/Cohort
Observational Cohort
no intervention



Primary Outcome Measures :
  1. Indicators of disease severity and progression - cardiac movement [ Time Frame: 2 years ]
    Establish the prevalence and severity of specific morbid indicators of disease severity through use of echocardiogram

  2. Indicators of disease severity and progression - cardiac function [ Time Frame: 2 years ]
    Establish the prevalence and severity of specific morbid indicators of disease severity through use of magnetic resonance imaging (MRI) of cardiac muscle

  3. Indicators of disease severity and progression - skeletal muscle function [ Time Frame: 2 years ]
    Establish the prevalence and severity of specific morbid indicators of disease severity through use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of skeletal muscle

  4. Indicators of disease severity and progression - skeletal muscle movement [ Time Frame: 2 years ]
    Establish the prevalence and severity of specific morbid indicators of disease severity through use of video scoring scale during exercise



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All participants in the study should have genetic confirmation or muslce biopsy confirmation along with supporting clinical features of mitochondrial disease with weakness in muscle.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05012358


Contacts
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Contact: Kaitlin Schwartz 507-293-9114 schwartz.kaitlin@mayo.edu
Contact: David Kveene 507-266-1920 kveene.david@mayo.edu

Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55901
Contact: Kaitlin Schwartz    507-293-9114    schwartz.kaitlin@mayo.edu   
Contact: David Kveene    507-266-6917    kveene.david@mayo.edu   
Principal Investigator: Ralitza Gavrilova, MD         
Sponsors and Collaborators
Mayo Clinic
Casimir, LLC
Astellas Pharma Inc
Investigators
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Principal Investigator: Ralitza Gavrilova, MD Mayo Clinic
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Responsible Party: Ralitza Gavrilova, Associate Professor of Medical Genetics and Neurology, College of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT05012358    
Other Study ID Numbers: 20-002721
First Posted: August 19, 2021    Key Record Dates
Last Update Posted: December 30, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ralitza Gavrilova, Mayo Clinic:
Mitochondrial DNA deletion
Additional relevant MeSH terms:
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Muscular Diseases
Mitochondrial Myopathies
Ophthalmoplegia, Chronic Progressive External
Kearns-Sayre Syndrome
Ophthalmoplegia
Mitochondrial Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Metabolic Diseases
Ocular Motility Disorders
Cranial Nerve Diseases
Paralysis
Neurologic Manifestations
Eye Diseases
Retinitis Pigmentosa
Retinal Dystrophies
Retinal Degeneration
Retinal Diseases
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases