Evaluation of Therapeutic Response in Spinal Muscular Atrophy Using Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)

February 26, 2020 updated by: University of Erlangen-Nürnberg Medical School
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: SMA patients (therapy arm)
  • Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 4 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors;
  • Magnetic Resonance Imaging (MRI) of lower leg
  • Physical assessment/milestones: expanded Hammersmith functional motor scale (HFMSE)/ Revised Upper Limb Module (RULM)/ 6-minute-walking-test (6-MWT)
Device: Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)
Non-invasive transcutaneous imaging of molecular muscle components
ACTIVE_COMPARATOR: SMA patients (control arm)
  • Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 4 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors;
  • Magnetic Resonance Imaging (MRI) of lower leg
  • Physical assessment/milestones: expanded Hammersmith functional motor scale (HFMSE)/ Revised Upper Limb Module (RULM)/ 6-minute-walking-test (6-MWT)
Device: Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)
Non-invasive transcutaneous imaging of molecular muscle components

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluation of muscle structure under therapy and change from baseline over time
Time Frame: 3 time points (at 0,2, and 12 months)
Comparison of the molecular muscle structure determined by MSOT and MRI in patients with SMA with and without treatment and evaluation of changes from baseline over time
3 time points (at 0,2, and 12 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Muscular lipid content
Time Frame: 3 time points (at 0,2, and 12 months)
Quantitative lipid signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA with and without therapy and change over time Units: arbitrary units (a.u.)
3 time points (at 0,2, and 12 months)
Muscular collagen content
Time Frame: 3 time points (at 0,2, and 12 months)
Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA with and without therapy and change over time Units: arbitrary units (a.u.)
3 time points (at 0,2, and 12 months)
Muscular hemo-/myoglobin content
Time Frame: 3 time points (at 0,2, and 12 months)
Quantitative hemo/myoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA with and without therapy and change over time Units: arbitrary units (a.u.)
3 time points (at 0,2, and 12 months)
Muscular de-/oxygenated hemo-/myoglobin content
Time Frame: 3 time points (at 0,2, and 12 months)
Quantitative de-/oxygenated hemo-/myoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA with and without therapy and change over time Units: arbitrary units (a.u.)
3 time points (at 0,2, and 12 months)
Ratio of lipid to hemo/myoglobin signal or collagen to hemo/myoglobin signal
Time Frame: 3 time points (at 0,2, and 12 months)
Ratio of quantitative lipid signal to hemo/myoglobin signal or collagen signal to hemo/myoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with SMA with and without therapy and change over time
3 time points (at 0,2, and 12 months)
T1 relaxation time
Time Frame: 3 time points (at 0,2, and 12 months)
T1 relaxation time determined by Magnetic Resonance Imaging (MRI) in patients with SMA with and without therapy and change over time
3 time points (at 0,2, and 12 months)
T2 relaxation time
Time Frame: 3 time points (at 0,2, and 12 months)
T2 relaxation time determined by Magnetic Resonance Imaging (MRI) in patients with SMA with and without therapy and change over time
3 time points (at 0,2, and 12 months)
Fat-water percentage
Time Frame: 3 time points (at 0,2, and 12 months)
Fat-water percentage determined by Magnetic Resonance Imaging (MRI) in patients with SMA with and without therapy and change over time
3 time points (at 0,2, and 12 months)
Sodium concentration
Time Frame: 3 time points (at 0,2, and 12 months)
Sodium concentration determined by Magnetic Resonance Imaging (MRI) in patients with SMA with and without therapy and change over time
3 time points (at 0,2, and 12 months)
Correlation of MSOT data with therapy status
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of the quantitative lipid/collagen/hemo/myoglobin and de-/oxygenated hemo-/myoglobin content determined by MSOT in patients with and without therapy and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MSOT data with clinical data (age/disease duration)
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of lipid/collagen/haemo/myoglobin and de-/oxygenated hemo-/myoglobin content determined by MSOT with disease duration/patient age and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MSOT data with physical assessment (HFMSE/RULM/6-MWT)
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of lipid/collagen/haemo/myoglobin and de-/oxygenated hemo-/myoglobin content determined by MSOT with HFMSE/Revised Upper Limb Module/6-MWT and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MRI data with therapy status
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of T1 relaxation time/T2 relaxation time/fat water portion/sodium concentration in patients with and without therapy and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MRI data with clinical data (age/disease duration)
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of T1 relaxation time/T2 relaxation time/fat water portion/sodium concentration with disease duration and patient age and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MRI data with physical assessment (HFMSE/RULM/6-MWT)
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of T1 relaxation time/T2 relaxation time/fat water portion/sodium concentration with HFMSE/Revised Upper Limb Module/6-MWT and evaluation of change over time
3 time points (at 0,2, and 12 months)
Correlation of MSOT data and MRI data
Time Frame: 3 time points (at 0,2, and 12 months)
Correlation of MSOT determined lipid/collagen/haemo/myoglobin and de-/oxygenated hemo-/myoglobin content and MRI derived T1 relaxation time/T2 relaxation time/fat water portion/sodium concentration and evaluation of change over time
3 time points (at 0,2, and 12 months)
Side differences
Time Frame: 3 time points (at 0,2, and 12 months)
Measurement of the signal differences in right / left comparison derived by Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI) and evaluation of change over time
3 time points (at 0,2, and 12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Erlangen-Nürnberg Medical School

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthias Türk, MD, University Hospital Erlangen, Department of Neurology
  • Principal Investigator: Armin Nagel, MD, University Hospital Erlangen, Department of Radiology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 25, 2020

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2021

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 453_19B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in the primary publication, after deidentification (text, tables, figures, and appendices)

IPD Sharing Time Frame

Beginning 9 months and ending 36 months following article publication.

IPD Sharing Access Criteria

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:

  • Individual participant data will not be available
  • Study Protocol and Statistical Analysis Plan will be available
  • The data will be available beginning 9 months and ending 36 months following article publication.
  • The data will be available to researchers who provide a methodologically sound proposal.
  • The data will be available for individual participant data meta-analysis, only.
  • Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de.

Restrictions may apply due to patient privacy and the General Data Protection Regulation.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings