Condition category
Injury, Occupational Diseases, Poisoning
Date applied
11/02/2019
Date assigned
19/02/2019
Last edited
28/02/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Traumatic brain injury (TBI) represents a major cause of injury-related death and disability, especially in the young population. Long term outcome includes many possible complications, including impaired thinking ability and emotional, behavioral, and personality disturbances.
This study is combining Cerebrolysin (CRB) treatment with repetitive transcranial magnetic stimulation (rTMS), in order to improve health outcomes in patients with moderate-severe TBI.

Who can participate?
Adults between 18 and 70-years old with a traumatic brain injury onset 30 days prior to screening.

What does the study involve?
Participants are invited to join this study at 30 days post TBI. After informing patients about study procedures, benefits and potential risks, consent is sought. All participants included in the study must pass the screening criteria and baseline evaluations. Individuals are then randomly allocated to one of three groups. The first group is administered Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS), the second group receives Cerebrolysin and sham rTMS, while the third group receives a placebo (saline solution) and sham rTMS.

What are the possible benefits and risks of participating?
Potential benefit of Cerebrolysin and repetitive transcranial magnetic stimulation administration in patients with TBI is improved mental and physical health. The main risk for patients is developing adverse events (AE). The severity of AEs 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?
The CAPTAIN-rTMS is a single centre trial run from Cluj-Napoca, Romania.

When has the study started and how long is it expected to run for?
April 2018 to May 2022

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

Who is the main contact?
1. Prof. Dr. Dafin Fior Muresanu, dafinm@ssnn.ro
2. Stefan Strilciuc, MPH, stefan.strilciuc@ssnn.ro

Trial website

Contact information

Type

Scientific

Primary contact

Prof Dafin Muresanu

ORCID ID

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

Contact details

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740066761
dafinm@ssnn.ro

Type

Public

Additional contact

Mr Stefan Strilciuc

ORCID ID

http://orcid.org/0000-0001-6112-0223

Contact details

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740066761
stefan.strilciuc@ssnn.ro

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

FSNN040418

Study information

Scientific title

Cerebrolysin and Repetitive Transcranial Magnetic Stimulation (Rtms) in Patients with Traumatic Brain Injury

Acronym

CAPTAIN-rTMS

Study hypothesis

Combining the repetitive transcranial magnetic stimulation with Cerebrolysin in cognitive rehabilitation of patients with traumatic brain injuries will improve cognitive function better than either treatment alone or placebo treatment.

Ethics approval

Approved 01/02/2018, Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy (8 Babeş Street, 400012 Cluj-Napoca, Romania; +40-264-597-256; contact@umfcluj.ro), ref: 2/08.01.2018. Amended 171/02.04.2018 (ref: 133/15.03.2018)

Amended 30/05/2019 (ref. 118/23.04.2019)

Study design

Monocentric randomized double-blind phase II study

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

Traumatic Brain Injury (TBI) onset 30 days prior to screening

Intervention

The synopsis of the study is organised in 3 visits:
1. Screening and Baseline - Study Day 30
2. Visit 1 - Study Day 101
3. Visit 2 - Study Day 180

No follow-up was performed after the 180-day evaluation. The study arms were administered the following treatment courses:

1. Treatment Group CRB + rTMS:
Days 31-40: 30 ml Cerebrolysin IV + rTMS
Days 61-70: 30 ml Cerebrolysin IV + rTMS
Days 91-100: 30 ml Cerebrolysin IV + rTMS
Cerebrolysin - diluted in 0.9% saline solution up to 250 ml
rTMS - stimulation parameters for left DLPFC: 10 Hz, 1,200 stimuli/day, intensity of 120% of resting motor threshold.

2. Treatment Group CRB + sham rTMS:
Days 31-40: 30 ml Cerebrolysin IV + sham rTMS
Days 61-70: 30 ml Cerebrolysin IV + sham rTMS
Days 91-100: 30 ml Cerebrolysin IV + sham rTMS
Cerebrolysin - diluted in 0.9% saline solution up to 250 ml

3. Treatment Group placebo + sham rTMS:
Days 31-40: Placebo IV + sham rTMS
Days 61-70: Placebo IV + sham rTMS
Days 91-100: Placebo IV + sham rTMS
Placebo: 250 ml 0.9% saline solution

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.
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 sponsor.
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.
Sham stimulation will be performed with a sham-coil (MCF-P-B 65, Magventure) which has a mechanical outline and sound level identical to MCF-B65, and also provides the same level of cutaneous discofort and muscle twiching as real stimulation. The rTMS (both sham and real) administration will be provided by two rTMS technicians which will not be involved in any further study-related procedures and will not be allowed to disclose any information about treatment procedure.

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 Sponsor 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 II

Drug names

Cerebrolysin

Primary outcome measure

1. Cognitive function assessed using Stroop Color-Word Test (Stroop, 1935) at days 30, 101, 180
2. Cognitive function assessed using Montreal Cognitive Assessment (MoCA) (Nasreddine, 2005) at days 30, 101, 180
3. Cognitive function assessed using PSI (Processing Speed Index, Wechsler adult intelligence scale – third edition) (Wechsler, 1997) at days 30, 101, 180
4. Cognitive function assessed using Digit Span (Wechsler adult intelligence scale – third edition) (Wechsler, 1997) at days 30, 101, 180
5. Cognitive function assessed using Trail Making Test (Reitan, 1958) at days 30, 101, 180
6. Emotional status assessed using Hamilton Anxiety Rating Scale (Hamilton, 1959) at days 30, 101, 180
7. Emotional status assessed using Hamilton Rating Scale for Depression (Hamilton, 1960) at days 30, 101, 180
8. Cognitive function assessed using One Touch Stockings of Cambridge at days 30, 101, 180
9. Cognitive function assessed using The Multitasking Test at days 30, 101, 180
10. Cognitive function assessed using Reaction Time at days 30, 101, 180

Secondary outcome measures

1. Eye movements assessed using a Tobii Pro TX300 eye-tracking device and analyzed using Tobii Studio software at 30, 101 and 180 days.
2. Brain electrical activity assessed using electoencephalography (EEG) and analyzed quantitatively using BrainAnalyzer software at 30, 101 and 180 days.
3. Adverse events of magnetic stimulation of the brain recorded using a tailored safety report form based on patient self-reports during the entire duration of the trial.

Overall trial start date

01/09/2017

Overall trial end date

31/05/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Traumatic brain injury onset 30 days prior to screening
2. CT/MRI – focal and/or diffuse lesions
3. Age: 18-70 years, inclusive (updated 28/02/2020: 18-80 years, inclusive)
4. Pre-Trauma Karnofsky Index 100
5. Willing and able to comply with the protocol requirements for the duration of the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

90

Participant exclusion criteria

1. Metal implant in the head or within the stimulation area
2. Medical implanted devices (cardiac pacemaker, cochlea implant or medication pumps)
3. History of intracranial interventions as well as ischemic or hemorrhagic stroke
4. Evidence of pre-existing major health problems (e.g., cancer, haematological, renal, hepatic, or coronary disease, psychiatric disorder, diabetes, myocardial infarction or other known heart diseases, disabling or musculoskeletal problems like rheumatoid arthritis, epilepsy, evidence of degenerative or inflammatory diseases affecting nervous system [e.g., Alzheimer, Parkinson]). Patients with well-controlled diabetes and hypertension can be included if there is no evidence of secondary damage to major organs.
5. Any neurological or non-neurological condition independent from TBI that might influence the functional outcome or other efficacy outcome measures.
6. Injury of writing hand influencing cognitive or other outcome measures, in the investigator’s judgment.
7. Clear clinical signs of intoxication influencing the evaluation, in the investigator’s judgment.
8. Major drug dependency including alcohol, in the investigator’s judgment.
9. Chronic treatment with steroids, Ca2+-channel blockers or major anticoagulants (e.g., warfarin and other coumarin derivates), monoamine oxidase inhibitors, antipsychotic drugs or nootropic molecules.
10. Patient with penetrating brain injury.
11. Females who are pregnant or lactating.
12. Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. Females of child bearing potential taking acceptable contraceptive precautions can be included. A highly effective method of birth control and one which is acceptable for this study, is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.

Recruitment start date

19/03/2018

Recruitment end date

31/12/2021

Locations

Countries of recruitment

Romania

Trial participating centre

“RoNeuro” Institute for Neurological Research and Diagnostic
No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Sponsor information

Organisation

EN: The foundation for the study of neuroscience and neuroregeneration (RO: Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)

Sponsor details

No. 37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740150076
office@ssnn.ro

Sponsor type

Research organisation

Website

http://www.ssnn.ro

Funders

Funder type

Research organisation

Funder name

EN: The foundation for the study of neuroscience and neuroregeneration (RO: Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)

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 current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

31/12/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

28/02/2020: The following changes were made to the trial record: 1. Ethics approval and inclusion criteria were updated. 2. The recruitment end date was changed from 31/12/2020 to 31/12/2021. 3. The overall trial end date was changed from 31/12/2020 to 31/05/2022. 4. The intention to publish date was changed from 31/12/2021 to 31/12/2022. 22/02/2019: Internal review.