Clinical trial NCT06221631: BrainAgeMS - a Comparative Study of Brain Aging in Healthy and Patients With Multiple Sclerosis
Official title: Brain Aging - a Comparative Study in Healthy and Patients With Multiple Sclerosis as Model of a Chronic Neuroinflammatory Disorder (BrainAgeMS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Brain Aging
Multiple Sclerosis
Neurodegeneration
Quantitative MRI
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Schweizerische Multiple Sklerose Gesellschaft
name: University of Bern
First posted: 2024-01-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Brain Age Gap in patients with MS
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Secondary outcomes:
measure: Relationship of brain age gaps with disease severity
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with gait speed
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with upper extremity function
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with sitting-to-raise time
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with cognitive symptoms
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with depression symptoms
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with fatigue
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
measure: Relationship of brain age gaps with quality of life
timeFrame: Up to 2 months after recruitment or finalization of MRI-visit, whichever came first.
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
affiliation: Head of the MS outpatient clinic
name: Robert Hoepner, PD Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.