Clinical trial NCT04115475: New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy
Official title: New Imaging Biomarkers for Muscular Diseases - Multispectral Optoacoustic Imaging in Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscular Diseases
Spinal Muscular Atrophy
Keywords: Muscular Diseases, Spinal Muscular Atrophy (SMA), MSOT
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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).

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.

Eligibility criteria: Inclusion Criteria:

* genetically proven SMA

Exclusion Criteria:

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

Primary outcomes:
measure: Spectral profile of muscle tissue
timeFrame: Single time point (1 day)
Secondary outcomes:
measure: Muscular lipid content
timeFrame: Single time point (1 day)
measure: Muscular collagen content
timeFrame: Single time point (1 day)
measure: Muscular myo-/hemoglobin content
timeFrame: Single time point (1 day)
measure: Muscular de-/oxygenated myo-/hemoglobin content
timeFrame: Single time point (1 day)
measure: Correlation of lipid signal with clinical data (age/disease duration)
timeFrame: Single time point (1 day)
measure: Correlation of collagen signal with clinical data (age/disease duration)
timeFrame: Single time point (1 day)
measure: Correlation of myo-/hemoglobin signal with clinical data (age/disease duration)
timeFrame: Single time point (1 day)
measure: Correlation of de-/oxygenated myo-/hemoglobin signal with clinical data (age/disease duration)
timeFrame: Single time point (1 day)
measure: Correlation of lipid signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
timeFrame: Single time point (1 day)
measure: Correlation of collagen signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
timeFrame: Single time point (1 day)
measure: Correlation of myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
timeFrame: Single time point (1 day)
measure: Correlation of de-/oxygenated myo-/hemoglobin signal with physical assessment (HINE/HFMSE/CHOP INTEND/ULM)
timeFrame: Single time point (1 day)
measure: Side differences of MSOT signals
timeFrame: Single time point (1 day)
measure: Correlation of RUCT and B-Mode Ultrasound
timeFrame: Single time point (1 day)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Pediatrics and Adolescent Medicine
state: Bavaria
Study officials:
affiliation: University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
name: Ferdinand Knieling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Erlangen, Department of Pediatric and Adolescent Medicine
name: Regina Trollmann, MD
role: PRINCIPAL_INVESTIGATOR
References: