Cerebral Small Vessel Disease Progression Dependent on Stroke Type (ZMA_BIO)

Biomarker-based Assessment of Cerebral Small Vessel Disease Progression After Lacunar and Territorial Stroke - a Prospective Cohort Study

The goal of this prospective, observational study is to understand if cerebral small vessel disease (CSVD) has different velocities and patterns of temporal development, dependent on a concurrent ischemic stroke. It focusses on adult patients with known or newly diagnosed CSVD on magnetic resonance imaging. The study will evaluate if blood based, in parts central nervous system specific protein markers, so called biomarkers, have an additional value reflecting the course of CSVD as defined per MRI assessments. Further patient-relevant endpoints include neuropsychological abilities, neurological functional outcomes, quality of life assessments, stroke recurrence risk.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Biomarkers; Cerebral Small Vessel Disease; Stroke Recurrence

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Mona E Laible, MD; Phone Number: +49(0)7311770; Email: mona.laible@uniklinik-ulm.de

Study Locations

• Germany
  • Baden-Wurttemberg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Recruiting
      • University Hospital Ulm, Department of Neurology, Germany
      • Contact: Mona E Laible, MD; Phone Number: +49(0)731 1770; Email: mona.laible@uniklinik-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with sporadic, non-genetic cerebral small vessel disease

Description

Inclusion Criteria:

• Age ≥ 18 years
• Evidence of cerebral small vessel disease on brain MRI, defined as white matter hyperintensities (Fazekas grade 1-3)
• Assignment to one of the following study groups based on MRI findings:
• cerebral small vessel disease without evidence of an acute ischemic stroke
• cerebral small vessel disease with acute lacunar ischemic stroke
• cerebral small vessel disease with acute territorial ischemic stroke
• Ability to provide written informed consent
• Sufficient German language skills to understand study procedures and assessments

Exclusion Criteria:

• Alternative plausible causes of white matter hyperintensities other than cerebral small vessel disease (e.g. inflammatory central nervous system disorders, leukodystrophies, brain tumors)
• Known neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's disease, other dementias)
• Acute or recent traumatic brain injury
• Contraindications to magnetic resonance imaging
• Pregnancy or breastfeeding
• Life expectancy of less than one year
• Inability to comply with study procedures or follow-up visits

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; cerebral small vessel disease without current stroke
Group 2; cerebral small vessel disease with acute lacunar stroke
Group 3; cerebral small vessel disease with acute territorial stroke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in White Matter Lesion Volume based on MRI measurements	MRI: White Matter Lesion volume will be measured and compared over the study trajectory (baseline upon study termination) in mm3	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Blood Biomarkers	Changes in blood biomarkers (e.g. NfL, GFAP, pTau in pg/ml)	1 year
Occurrence of Cerebrovascular Events	Cerebrovascular events during the follow-up period and their association with biomarker levels and MRI-based disease progression, defined as a binary outcome variable (e.g. for ischemic stroke, myocardial infarction, peripheral artery occlusion).	1 year
Changes in Neuropsychological Tests	Neuropsychological assessment focussing on attention, executive function, visual and verbal primary and working memory, as well as visuospatial function. For interpretation of results, z-scores will be applicable, as they are normalized according to age. A z-score of 0 equals the mean result of the normative population. A positive value indicates the data point is above the mean (a better performance than the mean results of the normatove population), while a negative value is below the mean. A score of -1.5 means the patient is 1.5 standard deviations below the mean, while a +1.0 is one SD above.	1 year
Neurological Functional Abilities	Using the modified Rankin Score (0-6, a higher score indicates a worse functional ability and an mRS of 6 indicates death)	1 year
Changes in Neurovascular Duplex/Dopplerultrasound	Neurovascular Duplex/Dopplerultrasound of extra-/intracranial brain-supplying arteries: changes in Plaque diameters (mm), Intima-Media-Thickness (IMT in mm, a higher IMT is associated with a more severe disease stage)	1 year
Stroke Severity	National Institutes of Stroke Health Scale (NIHSS, 0-42 points, a higher stroke indicates a more severe stroke)	1 year
Acitivies of Daily Living	ADL Score according to Katz (0-6)	1 year
EQ5D-5L	The EQ5D-5L ranges from a maximum of 1 (full health) to a minimum of roughly -0.661	1 year

Collaborators and Investigators

• Sponsor: Johannes Dorst
• Investigators: Study Chair: Mona E Laible, MD, University Hospital Ulm, Germany

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; biomarkers; cerebral small vessel disease
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Cerebral Small Vessel Diseases
• Other Study ID Numbers: ZMA_BIO; DRKS00038936 (Other Identifier: German Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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