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

NCT ID: NCT04115475

Last Updated: 2020-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-07
• Study Completion Date: 2020-01-30

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.

Conditions

Muscular Diseases; Spinal Muscular Atrophy

Keywords

Muscular Diseases, Spinal Muscular Atrophy (SMA), MSOT

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Multispectral Optoacoustic Tomography (MSOT)

Intervention Type: DEVICE

Non-invasive transcutaneous imaging of subcellular muscle components

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)

Group Type: EXPERIMENTAL

Multispectral Optoacoustic Tomography (MSOT)

Intervention Type: DEVICE

Non-invasive transcutaneous imaging of subcellular muscle components

Interventions

Multispectral Optoacoustic Tomography (MSOT)

Non-invasive transcutaneous imaging of subcellular muscle components

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• genetically proven SMA

Exclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ferdinand Knieling, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Erlangen, Department of Pediatric and Adolescent Medicine

Regina Trollmann, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Erlangen, Department of Pediatric and Adolescent Medicine

Locations

Department of Pediatrics and Adolescent Medicine

Erlangen, Bavaria, Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 38531362 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

168_19B

Identifier Type: -

Identifier Source: org_study_id