Muscular DiseasesMSOT_SMANCT04115475
New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy
A study testing Multispectral Optoacoustic Tomography (MSOT) in people with Muscular Diseases and Spinal Muscular Atrophy, run by University of Erlangen-Nürnberg Medical School at 1 site in Germany.
Trial 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). Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Muscular Diseases, Spinal Muscular Atrophy
- What is being tested?
- Multispectral Optoacoustic Tomography (MSOT)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 7 Nov 2019to 30 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- genetically proven SMA
Who cannot join
- Pregnancy
- Tattoo on skin to be examined
- For healthy volunteers only: suspected muscular disease/myopathia
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Pediatrics and Adolescent Medicine
Erlangen, Bavaria, 91054
About this study
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).
Read the 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.
- Conditions
- Muscular Diseases, Spinal Muscular Atrophy
- Being tested
- Multispectral Optoacoustic Tomography (MSOT)
- Keywords
- Muscular Diseases, Spinal Muscular Atrophy (SMA), MSOT
- Medical subject headings
- Muscular Diseases, Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multispectral Optoacoustic Tomography (MSOT)Device
Non-invasive transcutaneous imaging of subcellular muscle components
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteers (HV) | Active comparator | * 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) Receives: Device: Multispectral Optoacoustic Tomography (MSOT) |
| Spinal Muscular Atrophy (SMA) patients | Experimental | * 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) Receives: Device: Multispectral Optoacoustic Tomography (MSOT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spectral profile of muscle tissue
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.)
Measured: Single time point (1 day)
Secondary outcomes (14)
Muscular lipid content
Quantitative lipid signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)
Measured: Single time point (1 day)
Muscular collagen content
Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)
Measured: Single time point (1 day)
Muscular myo-/hemoglobin content
Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared to healthy control Units: arbitrary units (a.u.)
Measured: Single time point (1 day)
Muscular de-/oxygenated myo-/hemoglobin content
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.)
Measured: Single time point (1 day)
Correlation of lipid signal with clinical data (age/disease duration)
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))
Measured: Single time point (1 day)
Correlation of collagen signal with clinical data (age/disease duration)
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))
Measured: Single time point (1 day)
Correlation of myo-/hemoglobin signal with clinical data (age/disease duration)
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))
Measured: Single time point (1 day)
Correlation of de-/oxygenated myo-/hemoglobin signal with clinical data (age/disease duration)
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))
Measured: Single time point (1 day)
Correlation of lipid signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
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)
Measured: Single time point (1 day)
Correlation of collagen signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
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)
Measured: Single time point (1 day)
Correlation of myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
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)
Measured: Single time point (1 day)
Correlation of de-/oxygenated myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
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)
Measured: Single time point (1 day)
Side differences of MSOT signals
Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA compared between sides Units: arbitrary units (a.u.)
Measured: Single time point (1 day)
Correlation of RUCT and B-Mode Ultrasound
Quantitative grey scale signal derived by reflection mode ultrasound computed tomography (RUCT) correlated with grey scale B-Mode Ultrasound
Measured: Single time point (1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start7 Nov 2019
- Primary completion30 Jan 2020
- Study completion30 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscular DiseasesStudies of the same condition, open and under way.
- More trials run by University of Erlangen-Nürnberg Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ferdinand Knieling, MD, Principal investigator, University Hospital Erlangen, Department of Pediatric and Adolescent MedicineRegina Trollmann, MD, Principal investigator, University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04115475
- Sponsor's protocol ID
- 168_19B
- Acronym
- MSOT_SMA
- Status last verified
- Nov 2020
- First submitted
- 2 Oct 2019
- Last updated
- 18 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the primary publication, after deidentification (text, tables, figures, and appendices)
Publications
Nedoschill E, Wagner AL, Danko V, Buehler A, Raming R, Jungert J, Neurath MF, Waldner MJ, Rother U, Woelfle J, Trollmann R, Knieling F, Regensburger AP. Monitoring spinal muscular atrophy with three-dimensional optoacoustic imaging. Med. 2024 May 10;5(5):469-478.e3. doi: 10.1016/j.medj.2024.02.010. Epub 2024 Mar 25.
PubMed 38531362
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT04115475
- Acronym / sponsor ID
- MSOT_SMA / 168_19B
- Conditions
- Muscular Diseases, Spinal Muscular Atrophy
- Keywords
- Muscular Diseases, Spinal Muscular Atrophy (SMA), MSOT
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Erlangen-Nürnberg Medical SchoolUniversity, hospital or other
- Study start
- 7 Nov 2019 (actual)
- Primary completion
- 30 Jan 2020 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers (HV) | Active comparator | Device: Multispectral Optoacoustic Tomography (MSOT)* 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) |
| Spinal Muscular Atrophy (SMA) patients | Experimental | Device: Multispectral Optoacoustic Tomography (MSOT)* 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) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- genetically proven SMA
Key exclusion criteria (3 listed)
- Pregnancy
- Tattoo on skin to be examined
- For healthy volunteers only: suspected muscular disease/myopathia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multispectral Optoacoustic Tomography (MSOT)Non-invasive transcutaneous imaging of subcellular muscle components | Device | Healthy Volunteers (HV), Spinal Muscular Atrophy (SMA) patients |
Primary outcome
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.)
14 secondary outcomes
Muscular lipid content
Time frame: Single time point (1 day)
Muscular collagen content
Time frame: Single time point (1 day)
Muscular myo-/hemoglobin content
Time frame: Single time point (1 day)
Muscular de-/oxygenated myo-/hemoglobin content
Time frame: Single time point (1 day)
Correlation of lipid signal with clinical data (age/disease duration)
Time frame: Single time point (1 day)
Correlation of collagen signal with clinical data (age/disease duration)
Time frame: Single time point (1 day)
Correlation of myo-/hemoglobin signal with clinical data (age/disease duration)
Time frame: Single time point (1 day)
Correlation of de-/oxygenated myo-/hemoglobin signal with clinical data (age/disease duration)
Time frame: Single time point (1 day)
Correlation of lipid signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
Time frame: Single time point (1 day)
Correlation of collagen signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
Time frame: Single time point (1 day)
Correlation of myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
Time frame: Single time point (1 day)
Correlation of de-/oxygenated myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
Time frame: Single time point (1 day)
Side differences of MSOT signals
Time frame: Single time point (1 day)
Correlation of RUCT and B-Mode Ultrasound
Time frame: Single time point (1 day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2020.
- Derived from this study: PubMed 38531362Nedoschill E, Wagner AL, Danko V, Buehler A, Raming R, Jungert J, Neurath MF, Waldner MJ, Rother U, Woelfle J, Trollmann R, Knieling F, Regensburger AP. Monitoring spinal muscular atrophy with three-dimensional optoacoustic imaging. Med. 2024 May 10;5(5):469-478.e3. doi: 10.1016/j.medj.2024.02.010. Epub 2024 Mar 25.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the primary publication, after deidentification (text, tables, figures, and appendices)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ferdinand Knieling, MD principal investigator
University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
Regina Trollmann, MD principal investigator
University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multispectral Optoacoustic Tomography (MSOT) in people with Muscular Diseases and Spinal Muscular Atrophy, run by University of Erlangen-Nürnberg Medical School at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spectral profile of muscle tissue (time frame: Single time point (1 day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04115475, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020.