Establishment of Clinical Basis for Hematopoietic Growth Factors Therapy in Brain Injury

Study Overview
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Brief Summary
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The purpose of our study is to determine the safety and efficacy of the combination of erythropoietin (EPO) and granulocyte-colony stimulating factors (G-CSF) in patients with neurological diseases. To be specific, our clinical study is expected that the combination injection of EPO and G-CSF shows neurotrophic and neuroprotective effects by facilitating endogenous repair process in patients with neurological diseases including stroke, cerebral palsy, or atypical parkinsonism. Therefore, we will apply our original treatment technique in patients with neurological diseases, which is expected to overcome current ethical and technical limitations of less evidenced functional recovery, hematological changes, and side effects. Eventually, We will establish a comprehensive clinical background about neurotrophic and neuroprotective effects of this hematopoietic growth factors therapy.

Conditions
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Neurological Diseases, Ischemic Stroke, Hemorrhagic Stroke, Cerebral Palsy, Atypical Parkinson Disease

Intervention / Treatment
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* Drug: Combination injection of EPO and G-CSF
* Drug: Injection of normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 20 years old Voluntary participants Neurological diseases including stroke, cerebral palsy, or atypical parkinsonism, at least 3 months after their onset Participants who got previous EPO+GCSF injection at least 6 months ago. Exclusion Criteria: Under 20 years old Participants who can not voluntarily consent Encephalopathy including brain tumor and infection Warfarin (coumadin) medications Leukopenia, Thrombocytopenia, Polycythemia Malignant diseases, Malignant hypertension, Myeloproliferative disorder, Septic embolism, Hyperkalemia Hepatic or Renal dysfunction, Serum creatinine>3mg/dl Allergic reactions against to exogenous EPO and G-CSF Involved in a exclusion criteria for MRI test A women who is pregnant or on breast feeding Body temperature over 38°C Blood pressure over 140/90 mmHg at pre-treatment Blood pressure over 160/100 mmHg during intervention Hb > 15 g/dL at pre-treatment Hb > 17 g/dL during intervention Pneumonia detected by X-ray test Recurrent history of aspiration pneumonia

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention Group | Drug: Combination injection of EPO and G-CSF<br>* Subcutaneous EPO(300 U/kg)+G-CSF(10 μg/kg) injection once a day, 5 times a cycle (a week), total 3 cycles for 3 months.<br>|
| Placebo Comparator: Control<br>Control Group | Drug: Injection of normal saline<br>* Subcutaneous normal saline injection once a day, 5 times a cycle (a week), total 3 cycles for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital Sign | (1) Value of Systolic and Diastolic Blood Pressure, (2) Value of Pulse Rate, (3) Value of Respiratory Rate, (4) Value of Body Temperature. Vital Sign is tested to confirm the safety of the combination of EPO and G-CSF. | 5th day, 30th day during a cycle, and 6 months after pretest | 
| Hematological Test | (1) Value of Complete Blood Cells at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest, (2) Value of Reticulocyte at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest, (3) Value of Erythrocyte Sedimentation Rate at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest, (4) Value of C-Reactive Protein at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest, (5) Value of Electrolyte and Routine Chemistry at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest, (6) Value of Prothrombin Time and Activated Partial Thromboplastin Time at pre-treatment, 5th day, 30th day during a cycle (total three cycles), and 6 months after pretest. Hematological Test is tested to confirm the safety of the combination of EPO and G-CSF. | 5th day, 30th day during a cycle, and 6 months after pretest | 
| Chest and Heart Evaluation | (1) Chest X-ray finding at pre-treatment and 6 months after pretest, (2) Electrocardiography finding at pre-treatment and 6 months after pretest. Chest and Heart Evaluation is tested to confirm the safety of the combination of EPO and G-CSF. | at pre-treatment and 6 months after pretest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological Test | (1) Value of Erythropoietin Level, (2) Value of CD34+ cells. Value of Erythropoietin Level and CD 34+ Cells are tested to demonstrate the hematological changes and effectiveness of the combination of EPO and G-CSF. | 5th day, 30th day during a cycle, and 6 months after pretest | 
| Physical Assessment | (1) Score of Muscle Strength with Manual Muscle Testing, (2) Score of Joint Mobility with Range of Motion Test, (3) Score of Muscle Spasticity with Modified Ashworth Scale. Physical Assessment is tested to identify functional recovery of patients by neurotrophic and neuroprotective effects of the combination of EPO and G-CSF. | at pre-treatment, 3 months, and 6 months after pretest | 
| Occupational Assessment | Score of Activities of Daily Living with Modified Barthel Index, Functional Independence Measure. Occupational Assessments is tested to identify functional recovery of patients by neurotrophic and neuroprotective effects of the combination of EPO and G-CSF. | at pre-treatment, 3 months, and 6 months after pretest | 
| Psychological Assessment | Score of Psychological Status with Mini-Mental Status Examination, Memory Quotient, Geriatric Depression Scale, if necessary Psychological Assessments are tested to identify functional recovery of patients by neurotrophic and neuroprotective effects of the combination of EPO and G-CSF. | at pre-treatment and 6 months after pretest | 
| Verbal Assessment | Score of Verbal Function with Aphasia Quotient, Boston Naming Test, Multi-dimensional Voice Performance, if necessary. Verbal Assessments are tested to identify functional recovery of patients by neurotrophic and neuroprotective effects of the combination of EPO and G-CSF. | at pre-treatment and 6 months after pretest | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Growth Factors (EPO, G-CSF),, Neurological Diseases,, Neurorehabilitation,, Neurotrophic and Neuroprotective Effects