Cerebrolysin and Repetitive Transcranial Magnetic Stimulation (Rtms) in Patients with Traumatic Brain Injury
Traumatic Brain Injury (TBI) onset 30 days prior to screening
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 pre
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
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 vasectom