CERebrolysin In CADASIL

Study Overview
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Brief Summary
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The objective of this trial is the global risk-benefit assessment of Cerebrolysin as compared to Placebo in patients with genetically proven CADASIL. In addition, a traditional approach will be taken based on an evaluation of the separate risk and benefit domains in comparison with placebo.

Detailed Description
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Safety data area collected throughout the study (adverse events, vital signs and laboratory tests) and thereafter in case of ongoing serious adverse events (SAEs) at study endpoint. Optional secondary parameters include analyses of biomarkers (samples of blood, hair, urine, and saliva).

Official Title
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A Randomized, Double-blind, Single-centre, Two-period Cross-over, Placebo-controlled Trial on Safety and Efficacy in Patients With Genetically Proven CADASIL

Conditions
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Cadasil

Intervention / Treatment
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* Drug: Cerebrolysin
* Drug: 0.9 % NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of ≥18 years of age, all genders Diagnosis of CADASIL based on clinical symptoms, MRI, and genetic analysis MoCA >11 Adequate visual, auditory, and language skills (no language interpreter required) to follow study procedures Patient is not of childbearing potential (i.e. women are post-menopausal for two years, surgically sterile, or using adequate method of contraception) Patient participates voluntarily and gave written informed consent Exclusion Criteria: Any significant neurological disease/conditions other than CADASIL Focal lesions that may be responsible for the cognitive status of the patient (e.g. infectious disease, space-occupying lesion, normal pressure hydrocephalus) Any other diseases/conditions that may affect compliance with the protocol, such as: severe psychiatric disorders within the last three months delusional symptoms history of schizophrenia, schizoaffective disorder, bipolar affective disorder major depressive disorder newly identified within eight weeks before screening history of alcohol or substance abuse or dependence within the past two years Any circumstances that -in the investigator's opinion- may result in the patient's non-compliance with study procedures, e.g. fragile or thin veins that prevent many i.v. infusions Any other disease/conditions that may affect the safety assessment, such as: history of systemic cancer within the past two years history of myocardial infarction in the past year or unstable or severe cardiovascular disease (including uncontrolled hypertension and/or history of unstable hypertension not compensated by antihypertensive therapy) any clinically significant laboratory abnormalities at screening uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (HbA1c >87 mmol/mol) Use of concomitant medication with neuroprotective/neurotrophic/nootropic effects (e.g. ginkgo biloba, erythropoietin, citicoline, amantadine, piracetam) Any condition that would represent a contraindication for Cerebrolysin administration: hypersensitivity to one of the components of the drug epilepsy severe renal impairment (estimated Glomerular Filtration Rate [eGFR] <30 ml/min/1.73 m2 as assessed at local laboratory within one month before screening)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A two-period cross-over design, in which participants will be randomly allocated to either the Verum-Control sequence (sequence 1) or the Control-Verum sequence (sequence 2) in a 1:1 randomization.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Study group 1<br>Cerebrolysin - Placebo | Drug: Cerebrolysin<br>* 40 ml Cerebrolysin and 60 ml 0.9% NaCl per day for 4 days every month for 1 year<br>* Other names: Renacenz;Drug: 0.9 % NaCl<br>* 100 ml 0.9% NaCl per day for 4 days every month for 1 year<br>* Other names: Sodium Chloride;|
| Other: Study group 2<br>Placebo - Cerebrolysin | Drug: Cerebrolysin<br>* 40 ml Cerebrolysin and 60 ml 0.9% NaCl per day for 4 days every month for 1 year<br>* Other names: Renacenz;Drug: 0.9 % NaCl<br>* 100 ml 0.9% NaCl per day for 4 days every month for 1 year<br>* Other names: Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive battery (RAVLT) | - Rey Auditory Verbal Learning Test (AVLT) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (ROCF: Copy, immediate recall) | - Rey-Osterrieth Complex Figure Test (ROCF): Copy, immediate recall | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (Digit Symbol Coding, subscale of WAIS-PSI) | - Digit Symbol Coding (subscale of WAIS-PSI) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (Digit Span: Digit backward (subscale of WAIS-WMI) | - Digit Span: Digit backward (subscale of WAIS-WMI) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (Trail Making Test, Part B) | - Trail Making Test (Part B) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (ROCF: Delayed recall) | - Rey-Osterrieth Complex Figure Test (ROCF): Delayed recall | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (Stroop Color and Word Test - Prague Version) | - Stroop Color and Word Test - Prague Version (word/dots interference) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery (MoCA) | - Montreal Cognitive Assessment (MoCA) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in mood (Beck Depression Inventory-II) | - Beck Depression Inventory-II (BDI-II) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in imaging (White matter lesion volume) | - White matter lesion volume (MRI) | Baseline, Month 12, Month 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive battery, secondary outcome (Spatial Pattern Separation Task) | - Spatial Pattern Separation Task | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery, secondary outcome (Navigation Test Suite) | - Navigation Test Suite | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery, secondary outcome (Trail Making Test, Part A) | - Trail Making Test (Part A) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery, secondary outcome (Stroop Color and Word Test - Prague Version) | - Stroop Color and Word Test - Prague Version (color-word/dots interference) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery, secondary outcome (Symbol Search, subscale of WAIS-PSI) | - Symbol Search (subscale of WAIS-PSI) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in cognitive battery, secondary outcome (Digit Span: Digit forward, subscale of WAIS-WMI) | - Digit Span: Digit forward (subscale of WAIS-WMI) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in mood, secondary outcome (Beck Anxiety Inventory) | - Beck Anxiety Inventory | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in neurological deficits, secondary outcome (NIH stroke scale) | - NIH stroke scale (NIHSS) | Baseline, Month 6, Month 12, Month 21, Month 27 | 
| Change in imaging, secondary outcome (Index of general cortical thinning) | - Index of general cortical thinning (MRI) | Baseline, Month 12, Month 27 | 
| Change in imaging, secondary outcome (Post-stroke lacune volume) | - Post-stroke lacune volume (MRI) | Baseline, Month 12, Month 27 | 
| Change in biomarker analysis, secondary outcome (Neurofilament light chain) | - Neurofilament light chain (NFL) | Baseline, Month 12, Month 27 |