Imaging the Interplay Between Axonal Damage and Repair in Multiple Sclerosis

NCT05177523 | Recruiting

• 1 other identifier: 2018-01174; me18Granziera
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This project is to:

1. 1.Quantify differences in axonal integrity and organization in aMS versus naPMS patients.
2. 2.Quantify changes in axonal integrity and organization in aMS versus naPMS patients over a two-year period.
3. 3.Validate the combination of imaging parameters that best differentiate aMS versus naPMS patients using histopathology.

Conditions

Multiple Sclerosis (MS); Relapsing-remitting Multiple Sclerosis (RRMS); Secondary-progressive Multiple Sclerosis (SPMS); Primary Progressive Multiple Sclerosis (PPMS)

Keywords

axonal damage; axonal demyelination; axonal degeneration; axonal loss; axonal disorganization; axonal repair; axonal remyelination; axonal reorganization; Advanced MRI (aMRI); Neurite Orientation Dispersion and Density Imaging (NODDI); Diffusion Kurtosis (DK); Magnetization Transfer Imaging (MTI); Multi-echo Susceptibility-Based imaging (SBI); Myelin Water Imaging (MWI); T1 relaxometry (quantitative T1, qT1); machine learning technique

Outcome Measures

Primary Outcomes (1)

• MRI- change in axonal integrity and organization over 2 years in aMS, naPMS and HC, by using machine learning techniques

  After magnetic resonance (MR) data preprocessing (image denoising, standardization, bias field correction) classical machine learning techniques will be used to classify a number of MRI metrics which will be averaged over a number of regions of interest (ROIs) including (i) normal-appearing white and brain matter in brain lobes and cervical spinal cord, (ii) basal ganglia, (iii) thalamus, (vi) cerebellum, MS lesions. Complex input data (voxels/patches) will be generated to learn from, then a deep learning model for supervised classification will be defined to identify the combination of aMRI parameters that characterize aMS, naPMS and HC.

  at baseline and 2 years (+/- 3 months) after baseline

Secondary Outcomes (5)

• Change in MUSIC Test

  at baseline and 2 years (+/- 3 months) after baseline

• Change in auditory verbal learning and memory test/ Verbaler Lern- und Merkfähigkeitstest (VLMT)

  at baseline and 2 years (+/- 3 months) after baseline

• Change in Symbol Digital Modalities Test (SDMT)

  at baseline and 2 years (+/- 3 months) after baseline

• Change in Brief Visuospatial Memory Test (BVMT)

  at baseline and 2 years (+/- 3 months) after baseline

• Change in Hospital Anxiety and Depression Scale (HADS)

  at baseline and 2 years (+/- 3 months) after baseline

Study Arms (2)

MS patient group

Recruitment of 200 MS patients at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel)

Diagnostic Test: MRI; Other: blood sampling

control group (HC)

Recruitment of 100 healthy controls (HC) by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board.

Diagnostic Test: MRI; Other: Neurocognitive examination for healthy subjects; Other: blood sampling

Interventions

MRI DIAGNOSTIC_TEST

Each enrolled subject will undergo a MRI at baseline and a second MRI at 2 years (+/- 3 months) follow-up.

MS patient group; control group (HC)

Neurocognitive examination for healthy subjects OTHER

Neurocognitive examination for healthy subjects will be performed at both baseline and follow-up

control group (HC)

blood sampling OTHER

Each enrolled subject will undergo a blood sampling (10 ml) at baseline

MS patient group; control group (HC)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The recruitment of MS patients will take place at the MS Clinic of the Department of Neurology (Neurologische Klinik und Poliklinik), University Hospital Basel (Universitätsspital Basel). Healthy subjects will be recruited by public announcements (i.e. advertisement/flyer) on the University Hospital's and the University's notice board.

You may qualify if:

• Patients may be diagnosed with:
• active RRMS (n=100): Relapsing-remitting course and \> 1 clinical relapse and/or signs of MRI activity (\> 1 Gd enhancing lesion) during the last year before study enrollment.
• non-active PMS (n=100): Progressive course (PPMS or SPMS) and no clinical relapses and/or signs of MRI activity during the last year before study enrollment.
• Age 18-80 years old
• No other neurological or psychiatric disorder
• Age 18-80 years old
• No other neurological or psychiatric disorder

You may not qualify if:

• Pregnancy
• Contraindication to MRI (eg, claustrophobia, metallic implants, pacemaker etc).
• Inability to give consent

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (1)

University Hospital Basel, Department of Neurology

Basel, 4031, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be coded at acquisition and then aliquoted and stored at - 75 C

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Cristina Granziera, Prof. Dr. med.

  Department of Neurology, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Granziera, Prof. Dr. med.

CONTACT

+41 61-32 85 665; cristina.granziera@usb.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 4, 2022
• Study Start: September 4, 2018
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

CH (1)