Cerebrolysin in CADASIL

Phase 2

Recruiting

Conditions: Cerebral Autosomal Dominant Arteriopathy with subcortical Infarcts and Leukoencephalopathy (CADASIL)

Interventions: Drug: Cerebrolysin
Drug: 0.9 % NaCl

Registration Number: 2024-513828-42-00

Lead Sponsor: Ever Neuro Pharma GmbH

Brief Summary: The objective of this trial is the global risk-benefit assessment of Cerebrolysin as compared to Placebo in patients with genetically proven CADASIL.

Detailed Description: 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).

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 30

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 such as hormonal contraception in combination with a barrier method, the use of an intrauterine device or hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence)

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: a. severe psychiatric disorders within the last three months b. delusional symptoms c. history of schizophrenia, schizoaffective disorder, bipolar affective disorder d. major depressive disorder newly identified within eight weeks before screening e. 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: a. history of systemic cancer within the past two years b. 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) c. any clinically significant laboratory abnormalities at screening d. 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: a. hypersensitivity to one of the components of the drug b. epilepsy c. severe renal impairment (estimated Glomerular Filtration Rate [eGFR] <30 ml/min/1.73 m2 as assessed at local laboratory within one month before screening)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Study group 1	Cerebrolysin	Cerebrolysin - Placebo
Study group 1	0.9 % NaCl	Cerebrolysin - Placebo
Study group 2	Cerebrolysin	Placebo - Cerebrolysin
Study group 2	0.9 % NaCl	Placebo - Cerebrolysin

Primary Outcome Measures

Name	Time	Method
The primary multidimensional outcome ensemble comprises 10 single analysis variables of three dimensions (cognition, mood, imaging characteristics) assessed during and at the end of treatment phases I and II (at months 6, 12, 21, and 27). Month 12 (end of phase I) and Month 27 (end of phase II) are the primary endpoints of the formal cross-over analysis.		The primary multidimensional outcome ensemble comprises 10 single analysis variables of three dimensions (cognition, mood, imaging characteristics) assessed during and at the end of treatment phases I and II (at months 6, 12, 21, and 27). Month 12 (end of phase I) and Month 27 (end of phase II) are the primary endpoints of the formal cross-over analysis.

Secondary Outcome Measures

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

Trial Locations

Locations (1): Fakultni Nemocnice V Motole
🇨🇿
Prague, Czechia
Fakultni Nemocnice V Motole
🇨🇿Prague, Czechia
Aleš Tomek
Site contact
00420224436803
ales.tomek@gmail.com