Clinical trial NCT04262570: Evaluation of Therapeutic Response in Spinal Muscular Atrophy Using Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)
Official title: Evaluation of Therapeutic Response in Spinal Muscular Atrophy Using Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Muscular Diseases
Spinal Muscular Atrophy
Keywords: Muscular Diseases
Spinal Muscular Atrophy (SMA)
Multispectral Optoacoustic Tomography (MSOT)
Magnetic Resonance Imaging (MRI)
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2020-02-10
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This study aims to refine the capability of Multispectral Optoacoustic Tomography (MSOT) and Magnet Resonance Imaging (MRI) to characterise the molecular composition of muscle tissue non-invasively and to evaluate the therapeutic response in patients with spinal muscular atrophy (SMA) over time.

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 disease. However, most clinical trials lack primary outcomes other than clinical testing. Preliminary work shows that new methods such as multispectral optoacoustic tomography (MSOT) and magnetic resonance imaging (MRI) detect tissue changes very sensitively. Multispectral optoacoustic tomography (MSOT) is 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. In addition to this technology, MRI imaging has advanced in the field of muscle diseases, with 23Na-MRI being the first example. With both methods, the molecular composition of muscle tissue can be determined non-invasively and quantitatively at the same time. In this first pilot study on patients with SMA, the investigators will now assess whether the differences in the muscle composition of SMA patients with or without therapy can be quantified and whether they can be used simultaneously as markers during therapy with nusinersen (spinraza©) . Ideally, both techniques can complement or validate each other. In the future, this could generate a completely new, non-invasive method for evaluating endogenous biomarkers for therapy response.

Eligibility criteria: Inclusion Criteria:

* Genetically confirmed SMA type III
* From age 14
* Willingness and ability to participate, sufficient knowledge of the german language to understand the declaration of consent, or if not possible, information of the patient in his/her mother tongue or English
* High probability that the patients will be able to fully participate in the study (defined by the ability to lie still for about 1 hour and follow any breathing commands) For therapy arm: • Medical indication for Spinraza® therapy; start of study before first administration Spinraza® administration For control arm: • No medical indication for Spinraza® therapy

Exclusion Criteria:

* Pregnancy
* Tattoo on the skin area to be examined
* General contraindications for MRT examinations
* Electrical implants like pacemakers or perfusion pumps
* Pronounced claustrophobia
* Study participants with ferromagnetic or electrically conductive implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, heart valves with metal parts, metal splinters, tattoos next to the eye, symmetrical tattoos on the extremities or steel implants must consult the study physician; they may not be able to be examined (relative contraindications for MRI).
* Non-approved concomitant medication: strongly sedating medication must be excluded, as intensive monitoring of bodily functions during ongoing imaging cannot be guaranteed and the active participation of the test person might be necessary.

Primary outcomes:
measure: Evaluation of muscle structure under therapy and change from baseline over time
timeFrame: 3 time points (at 0,2, and 12 months)
Secondary outcomes:
measure: Muscular lipid content
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Muscular collagen content
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Muscular hemo-/myoglobin content
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Muscular de-/oxygenated hemo-/myoglobin content
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Ratio of lipid to hemo/myoglobin signal or collagen to hemo/myoglobin signal
timeFrame: 3 time points (at 0,2, and 12 months)
measure: T1 relaxation time
timeFrame: 3 time points (at 0,2, and 12 months)
measure: T2 relaxation time
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Fat-water percentage
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Sodium concentration
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MSOT data with therapy status
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MSOT data with clinical data (age/disease duration)
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MSOT data with physical assessment (HFMSE/RULM/6-MWT)
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MRI data with therapy status
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MRI data with clinical data (age/disease duration)
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MRI data with physical assessment (HFMSE/RULM/6-MWT)
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Correlation of MSOT data and MRI data
timeFrame: 3 time points (at 0,2, and 12 months)
measure: Side differences
timeFrame: 3 time points (at 0,2, and 12 months)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University Hospital Erlangen
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 Neurology
name: Matthias Türk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Erlangen, Department of Radiology
name: Armin Nagel, MD
role: PRINCIPAL_INVESTIGATOR
References: