Non-invasive Molecular Imaging of Muscle Structure (MSOT_muscles) (MSOT_muscles)

Non-invasive Molecular Imaging to Determine Hemoglobin and Collagen Levels in Muscles Before and After Exercise, and Over Time

This study aims to determine hemoglobin and collagen levels in muscles before and after exercise, and over time, using Multispectral Optoacoustic Tomography (MSOT). During MSOT, a transducer is placed on the skin similar to a conventional sonography and instead of sound, energy is supplied to the tissue by means of light flashes. This leads to a constant change of minimal expansions and contractions (thermoelastic expansion) of individual tissue constituents or molecules. The resulting sound waves can then be detected by the same examination unit.

Study Overview

• Status: Completed
• Conditions: Muscular Diseases
• Intervention / Treatment: Device: Multispectral Optoacoustic Tomography

Detailed Description

Duchenne muscular dystrophy (DMD) is one of the most common progressive childhood muscle diseases with an incidence of 1 in 3500 male newborns and is associated primarily with decreased life expectancy. Pathogenetically, there is a deficiency of dystrophin, a structural protein of the sarcolemma, which is caused by mutations (usually deletions) of the dystrophin gene (Xp21.3-p21.2). The result of dystrophin deficiency is a necrosis of muscle cells that are replaced by connective tissue and adipose tissue. Clinical scores (6-minute walk test, 6MWT) and MRI studies to characterize the degenerative changes of skeletal muscle in the early stages are available for the quantitative assessment of the disease progression as well as therapy effects, the significance of which is controversially discussed. However, the highly sensitive assessment of gene therapy effects will become increasingly important in the future. Sensitive, non-invasive methods for the detection of early muscle degeneration and muscle function in the course are of great clinical and scientific importance.

MSOT has already been demonstrated to be a potential monitoring tool in different diseases. However, it has not yet been investigated to what extent 1) previous physical activity 2) different measuring ranges at the muscle, 3) longitudinal measurements and 4) intra- and interoperative variability influences the measured results. In particular, molecular changes immediately after the 6-MWT are relevant for studies in patients with DMD.

In this first pilot study, the investigators want to investigate in healthy adults, whether increased exercise changes the hemoglobin values, whether the collagen content remains constant and whether repeated measurements at different muscle positions by different investigators provide consistent results over time. This information is indispensable for future studies of children with muscular diseases in order to be able to make statements about disease progression or even therapy response.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • University Hospital Erlangen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• >18 years of age

Exclusion Criteria:

• any reference to a myopathy
• pregnancy
• tattoo in the scanning region

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy Volunteers; Multispectral Optoacoustic Tomography (MSOT) of proximal and distal leg muscles (total of 12 sites: left and right, 3 measurement points of Musculus quadriceps, and 3 measurement points of Musculus triceps surae) before and after the 6-Minute-Walk-Test by to independent investigators. Repetition of the same protocol after 14 days.	Device: Multispectral Optoacoustic Tomography; Non-invasive transcutaneous imaging of subcellular muscle components

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular collagen content	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT.	one time point ( 2 measurements on day 1)
Muscular myo-/hemoglobin content	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT.	one time point ( 2 measurements on day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular oxygenated and deoxygenated myo-/hemoglobin content	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared before and after 6-MWT and after 14 days.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Intraindividual collagen content	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Intraindividual myo-/hemoglobin content	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Intraindividual oxygenated and deoxygenated myo-/hemoglobin content	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) compared between three different points in one muscle of one healthy volunteer	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Muscular collagen content in men and women	Quantitative collagen signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Muscular myo-/hemoglobin content in men and women	Quantitative myo-/hemoglobin signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Muscular oxygenated and deoxygenated myo-/hemoglobin content in men and women	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal of muscles derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in healthy men compared to healthy women.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Correlation of collagen signal with the 6-MWT	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Correlation of myo-/hemoglobin signal with the 6-MWT	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Correlation of oxygenated and deoxygenated myo-/hemoglobin signal with the 6-MWT	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in Healthy volunteers before and after exercise correlated with the 6-MWT	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interrater reliability of collagen content	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interrater reliability of myo-/hemoglobin content	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interrater reliability of oxygenated and deoxygenated myo-/hemoglobin content	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to investigators	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interreader reliability of collagen content	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interreader reliability of myo-/hemoglobin content	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Interreader reliability of oxygenated and deoxygenated myo-/hemoglobin content	Quantitative oxygenated and deoxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers before and after 6-MWT and after 14 days compared between to readers	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Muscular collagen content over time period	Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared between day 1 and after 14 days.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)
Muscular myo-/hemoglobin content over time period	Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in muscles of healthy volunteers compared between day 1 and after 14 days.	multiple time points ( 2 measurements on day 1 and 2 measurements on day 15)

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Adrian Regensburger, Dr., Department of Pediatrics and Adolescent Medicine, University of Erlangen; Principal Investigator: Ferdinand Knieling, Dr., Department of Pediatrics and Adolescent Medicine, University of Erlangen

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2019
• Primary Completion (ACTUAL): November 11, 2019
• Study Completion (ACTUAL): June 23, 2020

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (ACTUAL): June 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Muscular Diseases; MSOT; Duchenne muscular disease
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases
• Other Study ID Numbers: 169_19B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:

• Individual participant data will not be available
• Study Protocol and Statistical Analysis Plan will be available
• The data will be available beginning 9 months and ending 36 months following article publication.
• The data will be available to researchers who provide a methodologically sound proposal.
• The data will be available for individual participant data for meta-analysis, only.
• Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de.

Restrictions may apply due to patient privacy and the General Data Protection Regulation.

• IPD Sharing Time Frame: 36 months after publication
• IPD Sharing Access Criteria: Resonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No