Clinical trial NCT05755997: CERebrolysin In CADASIL
Official title: A Randomized, Double-blind, Single-centre, Two-period Cross-over, Placebo-controlled Trial on Safety and Efficacy in Patients With Genetically Proven CADASIL
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cadasil
Lead sponsor: Ever Neuro Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: idv Datenanalyse & Versuchsplanung
name: XClinical GmbH
First posted: 2023-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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. 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Patients of ≥18 years of age, all genders
2. Diagnosis of CADASIL based on clinical symptoms, MRI, and genetic analysis
3. MoCA \>11
4. Adequate visual, auditory, and language skills (no language interpreter required) to follow study procedures
5. Patient is not of childbearing potential (i.e. women are post-menopausal for two years, surgically sterile, or using adequate method of contraception)
6. Patient participates voluntarily and gave written informed consent

Exclusion Criteria:

1. Any significant neurological disease/conditions other than CADASIL
2. Focal lesions that may be responsible for the cognitive status of the patient (e.g.

   infectious disease, space-occupying lesion, normal pressure hydrocephalus)
3. Any other diseases/conditions that may affect compliance with the protocol, such as:

   1. severe psychiatric disorders within the last three months
   2. delusional symptoms
   3. history of schizophrenia, schizoaffective disorder, bipolar affective disorder
   4. major depressive disorder newly identified within eight weeks before screening
   5. history of alcohol or substance abuse or dependence within the past two years
4. 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
5. Any other disease/conditions that may affect the safety assessment, such as:

   1. history of systemic cancer within the past two years
   2. 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)
   3. any clinically significant laboratory abnormalities at screening
   4. uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (HbA1c \>87 mmol/mol)
6. Use of concomitant medication with neuroprotective/neurotrophic/nootropic effects (e.g. ginkgo biloba, erythropoietin, citicoline, amantadine, piracetam)
7. Any condition that would represent a contraindication for Cerebrolysin administration:

   1. hypersensitivity to one of the components of the drug
   2. epilepsy
   3. severe renal impairment (estimated Glomerular Filtration Rate \[eGFR\] \<30 ml/min/1.73 m2 as assessed at local laboratory within one month before screening)

Primary outcomes:
measure: Change in cognitive battery (RAVLT)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (ROCF: Copy, immediate recall)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (Digit Symbol Coding, subscale of WAIS-PSI)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (Digit Span: Digit backward (subscale of WAIS-WMI)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (Trail Making Test, Part B)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (ROCF: Delayed recall)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (Stroop Color and Word Test - Prague Version)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery (MoCA)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in mood (Beck Depression Inventory-II)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in imaging (White matter lesion volume)
timeFrame: Baseline, Month 12, Month 27
Secondary outcomes:
measure: Change in cognitive battery, secondary outcome (Spatial Pattern Separation Task)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery, secondary outcome (Navigation Test Suite)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery, secondary outcome (Trail Making Test, Part A)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery, secondary outcome (Stroop Color and Word Test - Prague Version)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery, secondary outcome (Symbol Search, subscale of WAIS-PSI)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in cognitive battery, secondary outcome (Digit Span: Digit forward, subscale of WAIS-WMI)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in mood, secondary outcome (Beck Anxiety Inventory)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in neurological deficits, secondary outcome (NIH stroke scale)
timeFrame: Baseline, Month 6, Month 12, Month 21, Month 27
measure: Change in imaging, secondary outcome (Index of general cortical thinning)
timeFrame: Baseline, Month 12, Month 27
measure: Change in imaging, secondary outcome (Post-stroke lacune volume)
timeFrame: Baseline, Month 12, Month 27
measure: Change in biomarker analysis, secondary outcome (Neurofilament light chain)
timeFrame: Baseline, Month 12, Month 27
Other outcomes:
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (hair, mean)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, mean)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (hair, mean)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (hair, greyish level)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, greyish level)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (hair, greyish level)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, day value)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, day value)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, day value)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, epigenetic age)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, omega-3 fatty acids)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, omega-3 fatty acids)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, omega-3 fatty acids)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (blood plasma)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (blood plasma)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (blood plasma)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (urine, alpha klotho)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, alpha klotho)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (urine, alpha klotho)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Serotonin level (urine, epigenetic markers)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, epigenetic markers)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in Cortisol level (urine, epigenetic markers)
timeFrame: Baseline, Month 12, Month 27
measure: Experimental (to be defined after study endpoint): Change in capillary permeability (Ktrans) in grey and white matter
timeFrame: Baseline, Month 12, Month 27
Locations:
city: Praha
country: Czechia
facility: Motol University Hospital
Study officials:
affiliation: Motol University Hospital
name: Aleš Tomek, MUDr., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: