Comprehensive Reparative Therapy in Ischemic Stroke COMplex Repair in Ischemic Stroke-Arm

Phase 4

• Conditions: Ischemic Stroke
• Interventions: Drug: Cerebrolysin infusion; Other: Placebo infusion

• Registration Number: NCT02581371
• Lead Sponsor: Clinical Institute of the Brain, Russia

Brief Summary

The aim of the present clinical phase IV study is to estimate the influence of Cerebrolysin in combination with standard therapy on the dynamics of recovery of the paretic upper limb in patients with acute ischemic stroke.

Each patient participates in the study for 176-190 days (approximately 6 months). The estimated duration of the study is 2 years.

Detailed Description

Rehabilitation programs and drug therapy in a stroke aimed, primarily, to the stimulation of the processes of neuroplasticity.

After the screening procedures the eligible patients get randomized in 1 of the 2 groups: either the group of a standard therapy in combination with Cerebrolysin infusions, or the group of a standard therapy in combination with placebo infusions.

The therapy consists of the 3 consecutive periods:

1. st - 10 days of daily infusions of Cerebrolysin / placebo;

2. nd - 7 days break;

3. d - 10 days of daily infusions of Cerebrolysin / placebo.

All participants will attend 7 Visits of the study (Visits 0, 1-6) at 2 sites respectively:

1. st - clinical center #1 - Sverdlovsk Regional Clinical Hospital #1, Ekaterinburg

2. nd - clinical center #2 - Clinical Institute of Brain, Ekaterinburg.

Patients will be transferred from the 1st site to the 2nd one at the moment of time between Visit 2 and Visit 3.

Patients will undergo traditional laboratory and clinical examination procedures and several specific ones such as scale NIHSS, modified Rankin scale, Barthel index, hand Frenchy assessments. All hand Frenchy assessments will be videotaped for later evaluation by an authorized researcher.

All participants will undergo the procedure of navigational transcranial magnetic stimulation of the brain NBS eXimia Nexstim with the use of an individual 3D brain model created on the Visit 0 MRI results basis.

Neither the patient nor the doctor will know whether they receive an investigational drug or placebo.

Study Timeline

• Study Start: 2015-02
• Status Verified: 2015-10
• Study First Submitted: 2015-10-19
• Study First Submitted QC: 2015-10-19
• Last Update Submitted: 2015-10-19
• Study First Posted: 2015-10-21
• Last Update Posted: 2015-10-21
• Primary Completion: 2017-02
• Study Completion: 2017-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

1. The age of 45 years or older than 75 years;
2. Known intolerance (including allergic reactions) Cerebrolysin, excipients of the investigational medication;
3. Thrombolytic therapy;
4. Signs of a hemorrhagic stroke;
5. Impairment of consciousness (≥ 2 points during the evaluation under item 1A NIHSS);
6. The presence of elements allowing to predict the resolution of neurological symptoms within 24 hours from the first symptoms;
7. Stroke or transient ischemic attack in history;
8. The score on the modified Rankin scale to a stroke more than 0 points;
9. Concomitant therapy or neuroprotective nootropic drugs;
10. New-onset seizures or epilepsy;
11. Planned carotid endarterectomy or other operations for secondary prevention of stroke;
12. Neurological disease or pathology of the neuromuscular system or any other disease that may affect the interpretation of study results;
13. Systemic therapy with biological drugs, including interferon, inductors and/or cytokine/anti-cytokine (e.g., anti-TNF, anti-CD4, IL-10, IL-1, etc.) within 1 month prior to screening;
14. Severe concomitant diseases, including cancer, which, in the opinion of the investigator, may affect the estimated parameters;
15. Uncontrolled hypertension (SBP ≥ 220 mm Hg. CL. and/or DBP ≥ 120 mm Hg. article in repeated measurements at the screening visit);
16. Uncontrolled angina, congestive heart failure or severe arrhythmia;
17. The presence of chronic infection (hepatitis B, C or AIDS) in the active form.
18. Severely impaired renal function or hepatic impairment (total bilirubin no more than 1.5 hvgn, the level of serum creatinine no more than 2.5 hugn and the levels of ALT, AST, GGT is not higher than 2.5 hvgn);
19. Diseases of the blood;
20. Mental illness, severe depression or suicide attempts in history;
21. The a history of drug addiction, alcoholism and abuse of drugs;
22. Contraindications to MRI: metal body, splinters, ferromagnetic implants (pacemakers, automatic dosing of drugs, implanted insulin pumps, artificial anus with a magnetic closure, artificial heart valves with metal elements), steel implants (clamps/clips on blood vessels, artificial joints, metal osteosynthesis devices), hearing AIDS;
23. Participation in any other clinical study within 30 days prior to screening or simultaneous participation in other clinical studies;
24. Pregnancy, breastfeeding or planning a pregnancy;
25. Women and men with preserved reproductive potential who refuse to use effective methods of contraception throughout the study;
26. Life expectancy less than 1 year;
27. Any disease or circumstances that, in the opinion of the investigator, may interfere with the subject participating in the study or in relation to which participation in the study may be dangerous for the subject;

Premature withdrowal criteria:

1. The research subject may discontinue participation at any time without giving a reason;
2. The researcher ahead of time to exclude the patient from the study in the following cases;
3. The refusal of the subject from further participation in the study;
4. Failure to comply with the subject rules of participation in the study;
5. The reasons that emerged during the study and threatening the security of the subject, including those associated with taking study medication adverse events;
6. The entities with during the study pregnancy;
7. The application of the patient in the study period of any additional neuroprotective and nootropic drugs, drugs from the group of correctors of cerebral blood flow;
8. Other reasons arising in the course of the study and prevent the realization of the study according to the Protocol;
9. Repeated stroke in the course of the study;
10. Subjects who are lost to observation, also belong to prematurely withdrawn from the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cerebrolysin infusion	Cerebrolysin infusion	Cerebrolysin, solution for injection, 10 ml vials. Two 10-day courses of 50 ml of investigational drug + 50 ml of sodium chloride 0.9% iv slowly drip infusions daily, separated with a 7-day interval
Placebo infusion	Placebo infusion	Sodium chloride 0.9%, solution for infusion, 100 ml. Two 10-day courses of 100 ml of sodium chloride 0.9% iv slowly drip daily, separated with a 7-day interval.

Primary Outcome Measures

Name	Time	Method
Overall dynamics of the hand function assessed by the Frenchay Arm Test	6 months	Visit 5 data comparison with Visit 0 data

Secondary Outcome Measures

Name	Time	Method
Dynamics of the hand function assessed by the Frenchay Arm Test	6 months	Visits 2,3,4 data comparison with Visit 0 data
Dynamics of the grades on the NIHSS scale	6 months	Visits 2,3,4,5 data comparison with Visit 0 data
Dynamics of the grades on the modified Rankin scale	6 months	Visits 2,3,4,5 data comparison with Visit 0 data
Dynamics of the Barthel index changes	6 months	Visits 2,3,4,5 data comparison with Visit 0 data
Dynamics of the cerebral infarction volume decrease according the 3D MRI data	6 months
Dynamics of the hemispheres cortex topology of palms motor centers according to navigated transcranial stimulation of the brain (NBS)	6 months	Visit 4, 5 data comparison with Visit 3 data
Dynamics of motor response threshold based on the results of navigated transcranial stimulation of the brain (NBS)	6 months
Dynamics of the amplitude of motor responses	6 months
Dynamics of the latency of motor responses	6 months
Frequency, nature and severity of adverse events.	6 months

Trial Locations

Locations (2)

Clinical Institute of Brain; 🇷🇺 Beryozovsky, Sverdlovsk region, Russian Federation

Sverdlovsk Regional Clinical Hospital #1; 🇷🇺 Ekaterinburg, Sverdlovsk region, Russian Federation