Condition category
Circulatory System
Date applied
10/04/2020
Date assigned
29/04/2020
Last edited
04/06/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Aphasia, a disorder that affects the ability to speak, understand, read or write, is a common symptom of acute ischemic stroke. In addition to speech therapy, this study investigates the effect of Cerebrolysin treatment on the recovery of post-stroke aphasia. Cerebrolysin is used in the treatment of ischemic strokes, brain trauma, organic, metabolic and neurodegenerative brain dysfunction. Previous research has suggested that Cerebrolysin acts by stimulating the brain's strengthening capacity, by promoting the survival of nervous system cells, neuronal communication and neurogenesis (the process by which neurons are born).

Who can participate?
Adults with speech disturbances post radiologically and clinically confirmed acute ischemic stroke with onset 3-5 days prior to screening

What does the study involve?
Participants are invited to join this study at 3-5 days after stroke onset. After informing patients about study procedures, benefits and potential risks, they sign a consent form. All participants included in the study must pass the screening criteria and baseline evaluations. Individuals are then allocated to one of two groups. The first group is administered 40 days of IV infusion of Cerebrolysin along with 1 hour/day speech therapy for 30 days, while the second group is administered placebo along with speech therapy.

What are the possible benefits and risks of participating?
By participating in this study, patients receive a free comprehensive evaluation and treatment program for post-ischemic stroke recovery. They will benefit from speech therapy sessions and may also benefit from Cerebrolysin treatment. The main risk for patients is developing adverse events (AE). Their severity and the causality to study medication is carefully assessed in order to establish a detailed safety profile of the intervention.

Where is the study run from?
ESCAS is a trial run from Cluj-Napoca (Romania)

When has the study started and how long is it expected to run for?
May 2020 to May 2022.

Who is funding the study?
The Society for the Study of Neuroprotection and Neuroplasticity (SSNN) (Romania)

Who is the main contact?
Dr Olivia Verisezan Rosu
olivia.rosu@ssnn.ro

Trial website

Contact information

Type

Scientific

Primary contact

Prof Dafin Fior Muresanu

ORCID ID

http://orcid.org/0000-0002-9536-1153

Contact details

37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740066761
dafinm@ssnn.ro

Type

Public

Additional contact

Dr Olivia Verisezan Rosu

ORCID ID

Contact details

37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40744820493
olivia.rosu@ssnn.ro

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

FSNN20200215

Study information

Scientific title

Efficacy and safety of Cerebrolysin in the treatment of aphasia after acute ischemic stroke

Acronym

ESCAS

Study hypothesis

Combining speech therapy with Cerebrolysin in rehabilitation of patients with acute ischemic stroke will improve aphasia better than speech therapy alone.

Ethics approval

Approved 27.03.2020, Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy (8 Babeş Street, 400012 Cluj-Napoca, Romania; +40 (0)264 597 256; contact@umfcluj.ro), ref: 122/24.03.2020.

Study design

Exploratory prospective randomized-controlled double-blinded trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Patients with Broca or mixed non-fluent aphasia post ischemic stroke with onset 3-5 days prior to inclusion

Intervention

The synopsis of the study is organised in 4 visits:
1. Screening and Baseline - Study Day 0 (3-5 days post stroke)
2. Visit 1 - Study Day 30
3. Visit 2 - Study Day 60
4. Visit 3 - Study Day 90

No follow-up is performed after the 90-day evaluation.

The study arms were administered the following treatment courses:

Previous interventions:
1. Control group:
1.1. 250 ml 0.9% saline solution administered by IV infusion as procedural placebo and speech therapy for 1h per day during the study period (40 treatment days)
2. Treatment group:
2.1. 30ml Cerebrolysin/day, diluted with 0.9% saline solution to a total solution of 250 ml, administered by IV infusion and speech therapy (1 h/day), 30 days during the study period
2.2. 10ml Cerebrolysin/day, diluted with 0.9% saline solution to a total solution of 250 ml, administered by IV infusion and speech therapy (1 h/day), 5 days/week, for 2 weeks (10 days) during the study period

Updated 04/06/2020:
1. Control group:
1.1. 250 ml 0.9% saline solution administered by IV infusion as procedural placebo and speech therapy for 1h per day during the study period (30 treatment days) – days 1-14, 29-42, 57-70
2. Treatment group:
2.1. 30ml Cerebrolysin/day, diluted with 0.9% saline solution to a total solution of 250 ml, administered by IV infusion and speech therapy (1 h/day), 30 treatment days – 1-14, 29-42, 57-70

Randomisation, Blinding, and Unblinding:
This study will be performed under double-blind conditions to keep investigators, other study personnel and patients blinded to treatment allocation. Cerebrolysin is an amber-colored solution; therefore, colored infusion lines will be used for drug administration.

A set of envelopes for each patient enrolled should be distributed to the study nurse preparing the ready-to-use-infusion solution. These nurses are only responsible for the preparation and administration of infusion solutions, and they should not be involved in any further study-related procedures. This person should not be allowed to disclose any information about treatment allocation. A treatment envelope should not be opened until the patient’s first ready-to-use-infusion has been prepared.

Patients meeting inclusion and exclusion criteria will obtain a random number corresponding to the random list generated in advance by a biometrician selected by the Coordinator. Based on the random list sealed, opaque randomization/emergency envelops will be provided as follows:
1. To the study center to break blinding if reasonable suspicion of harm to the patient exists
2. To the person assigned to prepare the ready-to-use-infusion
3. To the study coordinator

On opening, the randomization/emergency envelopes are dated (date, hour) and signed by the person who has opened the envelope. The Investigator should promptly document and explain to the Coordinator any premature unblinding of the Investigational Product(s). The whole study will be unblinded after closure of the database and determination of the analysis populations.


Intervention type

Drug

Phase

Phase IV

Drug names

Cerebrolysin

Primary outcome measure

Language function assessed by Western Aphasia Battery (Kertesz, 1979) at days 0, 30, 60, 90

Secondary outcome measures

1. Stroke severity assessed by NIH Stroke Scale (http://www.nihstrokescale.org/) at days 0, 30, 60, 90
2. Functional outcome assessed by Modified Rankin Score (van Swieten J et al., 1988) at days 0, 30, 60, 90
3. Activities of Daily Living assessed by Barthel Index (Mahoney et al., 1965) at days 0, 30, 60, 90

Overall trial start date

15/02/2020

Overall trial end date

31/08/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 04/06/2020:
1. Radiologically (CT or MRI) and clinically confirmed diagnosis of acute ischemic stroke in the left MCA territory
2. Broca or mixed non-fluent aphasia
3. Inclusion in the study between 3 and 5 days post-stroke
4. Right-handedness
5. Romanian as language of daily use
6. Signed informed consent

Previous inclusion criteria:
1. Radiologically (CT or MRI) and clinically confirmed diagnosis of acute ischemic stroke in the left MCA territory
2. Broca or mixed non-fluent aphasia
3. Inclusion in the study between 5 and 30 days post-stroke
4. Right-handedness
5. Romanian as language of daily use
6. Signed informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120

Participant exclusion criteria

1. Prior symptomatic ischemic or hemorrhagic stroke
2. Severe comprehension deficit that may compromise informed consent or understanding of instructions such as fluent aphasias (ex. Wernicke aphasia), or global aphasias
3. Contraindications to MRI
4. Preexisting neurodegenerative or psychiatric disease
5. Epilepsy or EEG-documented epileptic discharges
6. Severe chronic renal or liver failure; (AST, ALT > 4 times normal values, creatinine > 4)
7. Life-threatening diseases
8. Auditory or visual deficits that cannot be corrected and might impair testing

Recruitment start date

01/06/2020

Recruitment end date

31/05/2022

Locations

Countries of recruitment

Romania

Trial participating centre

County Emergency Hospital Cluj-Napoca
3-5 Clinicilor Street
Cluj-Napoca
400000
Romania

Trial participating centre

“RoNeuro” Institute for Neurological Research and Diagnostic
37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Sponsor information

Organisation

The foundation for the study of neuroscience and neuroregeneration (SSNN)

Sponsor details

(RO: Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)
37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740150076
office@ssnn.ro

Sponsor type

Research organisation

Website

https://www.ssnn.ro/

Funders

Funder type

Research organisation

Funder name

The foundation for the study of neuroscience and neuroregeneration

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/03/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

04/06/2020: The inclusion criteria, condition, interventions, and Plain English summary were updated to change "5-30 days post stroke onset" to "3-5 days post stroke onset". 16/04/2020: Trial’s existence confirmed by the Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy.