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CERebrolysin In CADASIL (CERICA)

Primary Purpose

Cadasil

Status
Not yet recruiting
Phase
Phase 2
Locations
Czechia
Study Type
Interventional
Intervention
Cerebrolysin
0.9 % NaCl
Sponsored by
Ever Neuro Pharma GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cadasil

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Motol University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Study group 1

Study group 2

Arm Description

Cerebrolysin - Placebo

Placebo - Cerebrolysin

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
February 14, 2023
Last Updated
September 28, 2023
Sponsor
Ever Neuro Pharma GmbH
Collaborators
idv Datenanalyse & Versuchsplanung, XClinical GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT05755997
Brief Title
CERebrolysin In CADASIL
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
March 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ever Neuro Pharma GmbH
Collaborators
idv Datenanalyse & Versuchsplanung, XClinical GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cadasil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study group 1
Arm Type
Other
Arm Description
Cerebrolysin - Placebo
Arm Title
Study group 2
Arm Type
Other
Arm Description
Placebo - Cerebrolysin
Intervention Type
Drug
Intervention Name(s)
Cerebrolysin
Other Intervention Name(s)
Renacenz
Intervention Description
40 ml Cerebrolysin and 60 ml 0.9% NaCl per day for 4 days every month for 1 year
Intervention Type
Drug
Intervention Name(s)
0.9 % NaCl
Other Intervention Name(s)
Sodium Chloride
Intervention Description
100 ml 0.9% NaCl per day for 4 days every month for 1 year
Primary Outcome Measure Information:
Title
Change in cognitive battery (RAVLT)
Description
- Rey Auditory Verbal Learning Test (AVLT)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (ROCF: Copy, immediate recall)
Description
- Rey-Osterrieth Complex Figure Test (ROCF): Copy, immediate recall
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (Digit Symbol Coding, subscale of WAIS-PSI)
Description
- Digit Symbol Coding (subscale of WAIS-PSI)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (Digit Span: Digit backward (subscale of WAIS-WMI)
Description
- Digit Span: Digit backward (subscale of WAIS-WMI)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (Trail Making Test, Part B)
Description
- Trail Making Test (Part B)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (ROCF: Delayed recall)
Description
- Rey-Osterrieth Complex Figure Test (ROCF): Delayed recall
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (Stroop Color and Word Test - Prague Version)
Description
- Stroop Color and Word Test - Prague Version (word/dots interference)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery (MoCA)
Description
- Montreal Cognitive Assessment (MoCA)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in mood (Beck Depression Inventory-II)
Description
- Beck Depression Inventory-II (BDI-II)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in imaging (White matter lesion volume)
Description
- White matter lesion volume (MRI)
Time Frame
Baseline, Month 12, Month 27
Secondary Outcome Measure Information:
Title
Change in cognitive battery, secondary outcome (Spatial Pattern Separation Task)
Description
- Spatial Pattern Separation Task
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery, secondary outcome (Navigation Test Suite)
Description
- Navigation Test Suite
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery, secondary outcome (Trail Making Test, Part A)
Description
- Trail Making Test (Part A)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery, secondary outcome (Stroop Color and Word Test - Prague Version)
Description
- Stroop Color and Word Test - Prague Version (color-word/dots interference)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery, secondary outcome (Symbol Search, subscale of WAIS-PSI)
Description
- Symbol Search (subscale of WAIS-PSI)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in cognitive battery, secondary outcome (Digit Span: Digit forward, subscale of WAIS-WMI)
Description
- Digit Span: Digit forward (subscale of WAIS-WMI)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in mood, secondary outcome (Beck Anxiety Inventory)
Description
- Beck Anxiety Inventory
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in neurological deficits, secondary outcome (NIH stroke scale)
Description
- NIH stroke scale (NIHSS)
Time Frame
Baseline, Month 6, Month 12, Month 21, Month 27
Title
Change in imaging, secondary outcome (Index of general cortical thinning)
Description
- Index of general cortical thinning (MRI)
Time Frame
Baseline, Month 12, Month 27
Title
Change in imaging, secondary outcome (Post-stroke lacune volume)
Description
- Post-stroke lacune volume (MRI)
Time Frame
Baseline, Month 12, Month 27
Title
Change in biomarker analysis, secondary outcome (Neurofilament light chain)
Description
- Neurofilament light chain (NFL)
Time Frame
Baseline, Month 12, Month 27
Other Pre-specified Outcome Measures:
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (hair, mean)
Description
- mean over several weeks
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, mean)
Description
- mean over several weeks
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (hair, mean)
Description
- mean over several weeks
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (hair, greyish level)
Description
- hair color (greyish level)
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (hair, greyish level)
Description
- hair color (greyish level)
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (hair, greyish level)
Description
- hair color (greyish level)
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, day value)
Description
- value of this time at this day
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, day value)
Description
- value of this time at this day
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, day value)
Description
- value of this time at this day
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (saliva, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (saliva, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (saliva, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, epigenetic age)
Description
- epigenetic age
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (blood pellet, omega-3 fatty acids)
Description
- omega-3 fatty acids
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (blood pellet, omega-3 fatty acids)
Description
- omega-3 fatty acids
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (blood pellet, omega-3 fatty acids)
Description
- omega-3 fatty acids
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (blood plasma)
Description
- somascan
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (blood plasma)
Description
- somascan
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (blood plasma)
Description
- somascan
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (urine, alpha klotho)
Description
- alpha klotho
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, alpha klotho)
Description
- alpha klotho
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (urine, alpha klotho)
Description
- alpha klotho
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Serotonin level (urine, epigenetic markers)
Description
- epigenetic markers
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Oxytocin level (urine, epigenetic markers)
Description
- epigenetic markers
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in Cortisol level (urine, epigenetic markers)
Description
- epigenetic markers
Time Frame
Baseline, Month 12, Month 27
Title
Experimental (to be defined after study endpoint): Change in capillary permeability (Ktrans) in grey and white matter
Description
Capillary permeability (Ktrans) in grey and white matter (MRI)
Time Frame
Baseline, Month 12, Month 27

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stefan Winter, Ph.D.
Phone
+1143 7665 20555
Ext
422
Email
Stefan.Winter@everpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aleš Tomek, MUDr., Ph.D.
Organizational Affiliation
Motol University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Motol University Hospital
City
Praha
ZIP/Postal Code
150 06
Country
Czechia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aleš Tomek, MUDr., Ph.D.
First Name & Middle Initial & Last Name & Degree
Aleš Tomek, MUDr., Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
No

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CERebrolysin In CADASIL

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