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New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy (MSOT_SMA)

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ClinicalTrials.gov Identifier: NCT04115475
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : November 12, 2019
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Brief Summary:
This study aims to refine the capability of MSOT to characterise muscle tissue and to determine non-invasive, quantitative biomarkers for the disease assessment in patients with spinal muscular atrophy (SMA) using Multispectral Optoacoustic Tomography (MSOT).

Condition or disease Intervention/treatment Phase
Muscular Diseases Spinal Muscular Atrophy Device: Multispectral Optoacoustic Tomography (MSOT) Not Applicable

Detailed Description:
SMA is an autosomal-recessive disorder, characterized by progressive muscle weakness and atrophy with an incidence of 1/10,000. The condition is caused by a homozygous deletion or mutation in the survival motor neuron 1 (SMN1), resulting in reduced expression of the survival motor neuron (SMN) protein. This leads to the degeneration of motor neurons in the spinal cord and brain stem. A nearby related gene, survival motor neuron 2 (SMN2), could partially compensate the loss of SMN1. Individuals with a higher copy number of SMN2 do in general have a milder phenotype. New therapeutic approaches, e.g. nusinersen (spinraza©), an antisense oligonucleotide medication that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene, are promising to help the formerly incurable children. However, most clinical trials lack primary outcomes other than clinical testing. At the moment there are no prospective, quantitative biomarkers available to detect muscle atrophy at an early age, and to follow up disease progression. As a new imaging modality, optoacoustic imaging (OAI) combines benefits of optical (high contrast) and acoustic (high resolution) imaging. Multispectral optoacoustic tomography (MSOT) is therefore capable of visualizing the distribution of endogenous absorbers by initiating laser-induced thermoelastic expansion and detection of resulting pressure waves. This imaging technique enables the label-free detection and quantification of different endogenous chromophores, such as melanin, hemoglobin, deoxyhemoglobin and lipids. Previously, it was demonstrated that MSOT is capable to monitor disease severity in Crohn's disease by detecting different signal levels of hemoglobin as markers of intestinal inflammatory activity. In this study we want to refine the capability of MSOT to characterize muscle tissue and to determine a non-invasive, quantitative biomarker for the disease assessment in SMA patients from birth using MSOT.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy
Actual Study Start Date : November 7, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020


Arm Intervention/treatment
Active Comparator: Healthy Volunteers (HV)
  • Multispectral Optoacoustic Tomography (MSOT) and B-Mode Ultrasound of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors;
  • physical assessment/milestones: Hammersmith Infant Neurological Examination (HINE)/ expanded Hammersmith functional motor scale (HFMSE)/ The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP Intend)/ Upper Limb Module (ULM)
Device: Multispectral Optoacoustic Tomography (MSOT)
Non-invasive transcutaneous imaging of subcellular muscle components

Experimental: Spinal Muscular Atrophy (SMA) patients
  • Multispectral Optoacoustic Tomography (MSOT) and B-Mode Ultrasound of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors;
  • physical assessment/milestones: Hammersmith Infant Neurological Examination (HINE)/ expanded Hammersmith functional motor scale (HFMSE)/ The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP Intend)/ Upper Limb Module (ULM)
Device: Multispectral Optoacoustic Tomography (MSOT)
Non-invasive transcutaneous imaging of subcellular muscle components




Primary Outcome Measures :
  1. Spectral profile of muscle tissue [ Time Frame: Single time point (1 day) ]
    Spectral profile of muscle tissue determined by multispectral optoacoustic tomography (MSOT) of patients with spinal muscular atrophy compared to healthy volunteers units: arbitrary units (a.u.)


Secondary Outcome Measures :
  1. Muscular lipid content [ Time Frame: Single time point (1 day) ]
    Quantitative lipid signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)

  2. Muscular collagen content [ Time Frame: Single time point (1 day) ]
    Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)

  3. Muscular myo-/hemoglobin content [ Time Frame: Single time point (1 day) ]
    Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)

  4. Muscular de-/oxygenated myo-/hemoglobin content [ Time Frame: Single time point (1 day) ]
    Quantitative de-/oxygenated myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)

  5. Correlation of lipid signal with clinical data (age/disease duration) [ Time Frame: Single time point (1 day) ]
    Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual clinical data (disease duration/age (in month))

  6. Correlation of collagen signal with clinical data (age/disease duration) [ Time Frame: Single time point (1 day) ]
    Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual clinical data (disease duration/age (in month))

  7. Correlation of myo-/hemoglobin signal with clinical data (age/disease duration) [ Time Frame: Single time point (1 day) ]
    Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual clinical data (disease duration/age (in month))

  8. Correlation of de-/oxygenated myo-/hemoglobin signal with clinical data (age/disease duration) [ Time Frame: Single time point (1 day) ]
    Quantitative de-/oxygenated myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual clinical data (disease duration/age (in month))

  9. Correlation of lipid signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM) [ Time Frame: Single time point (1 day) ]
    Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual physical assessment (HINE/HFMSE/CHOP INTEND/ULM)

  10. Correlation of collagen signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM) [ Time Frame: Single time point (1 day) ]
    Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual physical assessment (HINE/HFMSE/CHOP INTEND/ULM)

  11. Correlation of myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM) [ Time Frame: Single time point (1 day) ]
    Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual physical assessment (HINE/HFMSE/CHOP INTEND/ULM)

  12. Correlation of de-/oxygenated myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM) [ Time Frame: Single time point (1 day) ]
    Quantitative de-/oxygenated myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA correlated with individual physical assessment (HINE/HFMSE/CHOP INTEND/ULM)

  13. Side differences of MSOT signals [ Time Frame: Single time point (1 day) ]
    Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared between sides Units: arbitrary units (a.u.)

  14. Correlation of RUCT and B-Mode Ultrasound [ Time Frame: Single time point (1 day) ]
    Quantitative grey scale signal derived by reflection mode ultrasound computed tomography (RUCT) correlated with grey scale B-Mode Ultrasound



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • genetically proven SMA

Exclusion Criteria:

  • Pregnancy
  • Tattoo on skin to be examined
  • For healthy volunteers only: suspected muscular disease/myopathia

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): NCT04115475


Contacts
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Contact: Alexandra Wagner, MD +49 9131 85 33118 alexandra.l.wagner@uk-erlangen.de
Contact: Adrian Regensburger, MD +49 9131 85 33118 adrian.regensburger@uk-erlangen.de

Locations
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Germany
Department of Pediatrics and Adolescent Medicine Recruiting
Erlangen, Bavaria, Germany, 91054
Contact: Alexandra L Wagner, MD    +49 9131 8533118    alexandra.l.wagner@uk-erlangen.de   
Contact: Ferdinand Knieling, MD    +49 9131 8533118    ferdinand.knieling@uk-erlangen.de   
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
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Principal Investigator: Ferdinand Knieling, MD University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
Principal Investigator: Regina Trollmann, MD University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
  Study Documents (Full-Text)

Documents provided by University of Erlangen-Nürnberg Medical School:
Study Protocol  [PDF] November 7, 2019
Statistical Analysis Plan  [PDF] November 7, 2019


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Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT04115475    
Other Study ID Numbers: 168_19B
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: November 12, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in the primary publication, after deidentification (text, tables, figures, and appendices)
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication.
Access Criteria:

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 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.


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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 University of Erlangen-Nürnberg Medical School:
Muscular Diseases, Spinal Muscular Atrophy (SMA), MSOT
Additional relevant MeSH terms:
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Motor Neuron Disease
Muscular Diseases
Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Musculoskeletal Diseases