CERebrolysin In CADASIL

Cadasil Clinical Trial

— CERICA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05755997
• Other study ID #: EVER-CZ-0421
• Secondary ID: 2022-002394-29
• Status: Recruiting
• Phase: Phase 2
• Start date: November 29, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2023
• Source: Ever Neuro Pharma GmbH
• Contact: Stefan Winter, Ph.D.
• Phone: +1143 7665 20555
• Email: Stefan.Winter[@]everpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cadasil
• Dementia, Multi-Infarct

Intervention

Drug:
• Cerebrolysin
40 ml Cerebrolysin and 60 ml 0.9% NaCl per day for 4 days every month for 1 year
• 0.9 % NaCl
100 ml 0.9% NaCl per day for 4 days every month for 1 year

Locations

Country	Name	City	State
Czechia	Motol University Hospital	Praha

Sponsors (3)

Lead Sponsor	Collaborator
Ever Neuro Pharma GmbH	idv Datenanalyse & Versuchsplanung, XClinical GmbH

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (hair, mean)	- mean over several weeks	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, mean)	- mean over several weeks	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (hair, mean)	- mean over several weeks	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (hair, greyish level)	- hair color (greyish level)	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, greyish level)	- hair color (greyish level)	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (hair, greyish level)	- hair color (greyish level)	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, day value)	- value of this time at this day	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, day value)	- value of this time at this day	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, day value)	- value of this time at this day	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, epigenetic age)	- epigenetic age	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, omega-3 fatty acids)	- omega-3 fatty acids	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, omega-3 fatty acids)	- omega-3 fatty acids	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, omega-3 fatty acids)	- omega-3 fatty acids	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (blood plasma)	- somascan	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (blood plasma)	- somascan	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (blood plasma)	- somascan	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (urine, alpha klotho)	- alpha klotho	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, alpha klotho)	- alpha klotho	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (urine, alpha klotho)	- alpha klotho	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Serotonin level (urine, epigenetic markers)	- epigenetic markers	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, epigenetic markers)	- epigenetic markers	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in Cortisol level (urine, epigenetic markers)	- epigenetic markers	Baseline, Month 12, Month 27
Other	Experimental (to be defined after study endpoint): Change in capillary permeability (Ktrans) in grey and white matter	Capillary permeability (Ktrans) in grey and white matter (MRI)	Baseline, Month 12, Month 27
Primary	Change in cognitive battery (RAVLT)	- Rey Auditory Verbal Learning Test (AVLT)	Baseline, Month 6, Month 12, Month 21, Month 27
Primary	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
Primary	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
Primary	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
Primary	Change in cognitive battery (Trail Making Test, Part B)	- Trail Making Test (Part B)	Baseline, Month 6, Month 12, Month 21, Month 27
Primary	Change in cognitive battery (ROCF: Delayed recall)	- Rey-Osterrieth Complex Figure Test (ROCF): Delayed recall	Baseline, Month 6, Month 12, Month 21, Month 27
Primary	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
Primary	Change in cognitive battery (MoCA)	- Montreal Cognitive Assessment (MoCA)	Baseline, Month 6, Month 12, Month 21, Month 27
Primary	Change in mood (Beck Depression Inventory-II)	- Beck Depression Inventory-II (BDI-II)	Baseline, Month 6, Month 12, Month 21, Month 27
Primary	Change in imaging (White matter lesion volume)	- White matter lesion volume (MRI)	Baseline, Month 12, Month 27
Secondary	Change in cognitive battery, secondary outcome (Spatial Pattern Separation Task)	- Spatial Pattern Separation Task	Baseline, Month 6, Month 12, Month 21, Month 27
Secondary	Change in cognitive battery, secondary outcome (Navigation Test Suite)	- Navigation Test Suite	Baseline, Month 6, Month 12, Month 21, Month 27
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in mood, secondary outcome (Beck Anxiety Inventory)	- Beck Anxiety Inventory	Baseline, Month 6, Month 12, Month 21, Month 27
Secondary	Change in neurological deficits, secondary outcome (NIH stroke scale)	- NIH stroke scale (NIHSS)	Baseline, Month 6, Month 12, Month 21, Month 27
Secondary	Change in imaging, secondary outcome (Index of general cortical thinning)	- Index of general cortical thinning (MRI)	Baseline, Month 12, Month 27
Secondary	Change in imaging, secondary outcome (Post-stroke lacune volume)	- Post-stroke lacune volume (MRI)	Baseline, Month 12, Month 27
Secondary	Change in biomarker analysis, secondary outcome (Neurofilament light chain)	- Neurofilament light chain (NFL)	Baseline, Month 12, Month 27