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

Spinal Muscular Atrophy Clinical Trial

— MSOT_SMA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04115475
• Other study ID #: 168_19B
• Status: Completed
• Phase: N/A
• Start date: November 7, 2019
• Est. completion date: January 30, 2020

Study information

• Verified date: November 2020
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 30, 2020
• Est. primary completion date: January 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• genetically proven SMA

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Muscular Diseases
• Spinal Muscular Atrophy

Intervention

Device:
• Multispectral Optoacoustic Tomography (MSOT)
Non-invasive transcutaneous imaging of subcellular muscle components

Locations

Country	Name	City	State
Germany	Department of Pediatrics and Adolescent Medicine	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)	Single time point (1 day)
Secondary	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.)	Single time point (1 day)
Secondary	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.)	Single time point (1 day)
Secondary	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.)	Single time point (1 day)
Secondary	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.)	Single time point (1 day)
Secondary	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))	Single time point (1 day)
Secondary	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))	Single time point (1 day)
Secondary	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))	Single time point (1 day)
Secondary	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))	Single time point (1 day)
Secondary	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)	Single time point (1 day)
Secondary	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)	Single time point (1 day)
Secondary	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)	Single time point (1 day)
Secondary	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)	Single time point (1 day)
Secondary	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.)	Single time point (1 day)
Secondary	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	Single time point (1 day)