BrainAgeMS - a Comparative Study of Brain Aging in Healthy and Patients With Multiple Sclerosis (BrainAgeMS)

Brain Aging - a Comparative Study in Healthy and Patients With Multiple Sclerosis as Model of a Chronic Neuroinflammatory Disorder (BrainAgeMS)

The purpose of this study is to investigate new quantitative MRI-sequences for assessment of age-specific data for the prediction of brain aging.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis

Detailed Description

After being informed about the study, healthy controls and patients with multiple sclerosis giving written informed consent will undergo blood examination (for determination of the biological age using the publicly available R-package algorithm BioAge), clinical examination (for motor, cognitive and psychological parameters) as well as an MRI-investigation with chemical exchange saturation transfer (CEST) and T1-relaxometry on a 7 Tesla MRI. Data from the healthy controls will be used to set up a normative brain age data set, that could be used for example to train a model for brain age prediction.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Alejandro X. León Betancourt, Dr.med.; Phone Number: +41316326093; Email: alejandro.betancourt@insel.ch
• Study Contact Backup: Name: Piotr Radojewski, Dr.med.; Phone Number: +41316326093; Email: piotr.radojewski@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
    • Contact: Alejandro X. León Betancourt, Dr.med.; Phone Number: +41 31 632 60 93; Email: alejandro.betancourt@insel.ch
    • Sub-Investigator: Alejandro X. León Betancourt, Dr.med.
    • Principal Investigator: Robert Hoepner, PD Dr.med.
    • Sub-Investigator: Piotr Radojewski, Dr.med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Group 1: recruitment from the general population through advertisement Group 2: recruitment primarily from the outpatient MS consultation in Inselspital

Description

Inclusion Criteria:

Informed Consent signed by the subject

• Group 1: Any healthy individual between 18 and 65 years of age
• Group 2: Any individuals with any diagnosis of Multiple Sclerosis between 18 and 65 years of age and EDSS ≤6.0.

Exclusion Criteria:

• Group 1 and 2: Any other neurological disease except primary headaches: insufficient language skills in German or French; pregnancy, lactation, any contraindication for MRI (active implants, passive ferromagnetic implants, passive non-ferromagnetic metallic implants >4cm in the region covered by the active RF coils, large tattoos inside a region covered by the active radiofrequency (RF) coils, claustrophobia or suspected/known non-compliance), smoking within the last 10 years prior recruitment, any other drug consumption except moderate alcohol intake (less than a standard drink containing 10 grams of alcohol per day) or use of medical cannabis, any previous head trauma (with known/suspected intracranial consequences), Body Mass Index (BMI) >30, and any other chronic progressive disease.

  • Specific Criteria for group 1: The calculated biological age (BioAge R Package algorithm) differs by > +/- 3 years from the chronological age. These patients will not be further invited for a study visit with clinical examination and MRI.
  • Specific Criteria for group 2: EDSS > 6.0 as this impacts physical testing; clinical relapse within the last 6 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group 1: Healthy Controls; Healthy individuals with a predefined healthy lifestyle (s. inclusion/exclusion criteria), without any progressive disease or any neurological disorder (aside from primary headaches)
Group 2: Patients with Multiple Sclerosis; Patients with MS with a similar healthy lifestyle (s. inclusion/exclusion criteria), who are able to walk without more than one-sided walking aid (max. EDSS of 6 points), no relapse activity in the last 6 months, without any other progressive disease or other neurological disorder (aside from primary headaches)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Age Gap in patients with MS	Difference between estimated brain age and (A) biological as well as (B) chronological age.	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship of brain age gaps with disease severity	Relationship of brain age gaps with disease severity as measured by the expanded disability and severity scale (EDSS; min.-max. according to eligibility criteria: 0-6 points, with a higher score meaning a higher degree of disease severity)	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with gait speed	Relationship of brain age gaps with gait speed as measured by the 25-foot walking test	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with upper extremity function	Relationship of brain age gaps with upper extremity function as measured by the 9-hole Peg Test	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with sitting-to-raise time	Relationship of brain age gaps with a raising test using the sitting-to-raise time	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with cognitive symptoms	Relationship of brain age gaps with cognitive (brief international cognitive assessment in multiple sclerosis (BICAMS))	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with depression symptoms	Relationship of brain age gaps with depression symptoms as assessed with the brief depression inventory (BDI)	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with fatigue	Relationship of brain age gaps with fatigue as assessed with the fatigue severity score (FSS)	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Relationship of brain age gaps with quality of life	Relationship of brain age gaps with experienced quality of life as assessed with the Multiple Sclerosis Impact Scale (MSIS)-29	Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: University of Bern; Schweizerische Multiple Sklerose Gesellschaft
• Investigators: Principal Investigator: Robert Hoepner, PD Dr.med., Head of the MS outpatient clinic

Publications and helpful links

General Publications

• Piredda GF, Caneschi S, Hilbert T, Bonanno G, Joseph A, Egger K, Peter J, Kloppel S, Jehli E, Grieder M, Slotboom J, Seiffge D, Goeldlin M, Hoepner R, Willems T, Vulliemoz S, Seeck M, Venkategowda PB, Corredor Jerez RA, Marechal B, Thiran JP, Wiest R, Kober T, Radojewski P. Submillimeter T1 atlas for subject-specific abnormality detection at 7T. Magn Reson Med. 2023 Apr;89(4):1601-1616. doi: 10.1002/mrm.29540. Epub 2022 Dec 7.
• Mennecke A, Khakzar KM, German A, Herz K, Fabian MS, Liebert A, Blumcke I, Kasper BS, Nagel AM, Laun FB, Schmidt M, Winkler J, Dorfler A, Zaiss M. 7 tricks for 7 T CEST: Improving the reproducibility of multipool evaluation provides insights into the effects of age and the early stages of Parkinson's disease. NMR Biomed. 2023 Jun;36(6):e4717. doi: 10.1002/nbm.4717. Epub 2022 Mar 17.
• Kwon D, Belsky DW. A toolkit for quantification of biological age from blood chemistry and organ function test data: BioAge. Geroscience. 2021 Dec;43(6):2795-2808. doi: 10.1007/s11357-021-00480-5. Epub 2021 Nov 2.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 14, 2024
• First Posted (Estimated): January 24, 2024

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 14, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Neurodegeneration; Quantitative MRI; Brain Aging
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: ethic number 2023-D0110; 10001315 (Other Identifier: Swissmedic); CIV-23-12-045014 (Other Identifier: EUDAMED)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participants data that underlie results in a publication, after deidentification
• IPD Sharing Time Frame: Starting 9 months and ending 48 months after publication

IPD Sharing Access Criteria

Encoded data will be provided only to investigators who provide a methodologically sound proposal to achieve the aims in the approved proposal.

Proposals should be directed to brainage@ikmail.com. To gain access, data requestors will need to sign a data access agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No