Acute Stroke
Conditions
Keywords
Stroke
Brief summary
The purpose of this study is to assess the safety of Beta-hCG + Erythropoietin in patients with acute ischemic stroke.
Detailed description
Patients with a new stroke will be evaluated at the University of California Irvine Medical Center (UCIMC), a JCAHO-certified Stroke Center, and at Hoag Memorial Hospital Presbyterian. Standard stroke pathways will be used to identify such patients and to initiate standard of care therapy. Patients potentially eligible for study enrollment will be identified, screened, then consented and enrolled. Those meeting all entry criteria, and no exclusion criteria, will undergo additional baseline testing including brain MRI. A 9-day course of B-E therapy will then begin, always within 48 hours after stroke onset. This therapy will consist of hCG (3 once-daily IM doses at 10,000 IU per dose, one day apart, on days 1, 3 and 5 of study participation), followed by a one day washout period (day 6), followed by Epo (three once-daily i.v. doses at 30,000 IU per dose on days 7, 8, and 9 of study participation). Patients will be examined at several time points during therapy, as well as 6 weeks and 3 months after stroke onset. The primary outcome measures are related to safety, while secondary outcome measures are related to disability, neurological status, and MRI measures.
Interventions
DRUGDual Growth Factor
10,000 IU Beta-hCG IV on days 1, 3, and 5 of study participation 30,000 IU Erythropoietin IV on days 7, 8 and 9 of study participation
Sponsors
Stem Cell Therapeutics Corp.
Hoag Memorial Hospital Presbyterian
University of California, Irvine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age 21-85 2. NIHSS score 6-24 at time of enrollment, ensuring that stroke is neither mild nor devastating 3. Stroke is ischemic in origin, supratentorial, and radiologically confirmed 4. Patient is 24-48 hours from time of stroke onset at time that first dose of B-E therapy is administered. Time of onset is when symptoms began, and stroke occurred during sleep, time of onset is when patient was last seen to be normal. 5. Reasonable expectation of availability to receive the full 9 day B-E therapy course 6. Reasonable expectation that patient will receive standard post-stroke physical, occupational, speech, and cognitive therapy as indicated
Exclusion criteria
1. Pre-existing and active major psychiatric or other neurological disease 2. History of significant alcohol or drug abuse in the prior 3 years 3. Serum hemoglobin \> 16 g/dL in a male patient or \> 14 g/dL in a female patient; or a platelet count \> 400,000/mm3 in either a male or female patient 4. Advanced liver, kidney, cardiac, or pulmonary disease; the former will be operationally defined as a serum bilirubin \> 4 mg/dL, alkaline phosphatase \> 250 U/L, SGOT \> 150 U/L, SGPT \>150 U/L, or creatinine \> 3.5 mg/dL 5. Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female in reproductive years, using a test that reliably detects beta-hCG levels \> 25 with normal levels being \< 8 IU/L. 6. Contraindication to study participation on the basis of any of the following: 1. Allergy or other contraindication to initiating either beta-hCG or Erythropoietin 2. Known hypersensitivity to mammalian cell-derived products or hypersensitivity to albumin 3. A known diagnosis of prostatic cancer; note that prostate specific antigen will be collected for retrospective assessment of safety, but will not be used to ascertain study eligibility 4. Dysuria of unexplained origin 5. Uncontrolled hypertension, defined in the context of acute stroke as blood pressure persistently above 220 mm Hg systolic or 120 diastolic despite antihypertensive therapy 7. Current use of either beta-hCG or Erythropoietin 8. Other condition known to elevate beta-hCG, active in the prior 24 months, e.g., choriocarcinoma or germ cell tumor 9. Terminal medical diagnosis consistent with survival \< 1 year 10. Known hypercoagulable state, which for the purposes of this study will deficiency of proteins C, S, or antithrombin III; activated protein C resistance; prothrombin gene mutation; or an anti-phospholipid antibody syndrome as based on clinical and laboratory measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 3 mo | Safety through Day 90 was assessed through adverse event reporting, serial examinations, blood testing, and a leg vein Doppler at Day 42. Number of participants who experienced adverse events, had abnormality in serial examinations, blood testing, and a leg vein Doppler at Day 42. |
| Morbidity | 3 mo | attributable to experimental intervention |
| Mortality | 3 mo | attributable to experimental intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fugl-Meyer Leg Scale | 3 mo. | Measure of leg motor impairment with three subsections which are Proximal, Hip/Knee, and Speed/Coordination. The scale ranges from 0-34 with a higher score being better. A score of 34 is considered normal. |
| Boston Naming Test | 3 mo | Measure of aphasia or other language disturbance caused by stroke or other dementing disorders. It consists of 60 line drawings graded in difficulty in which patients are to name each picture. |
| Line Cancellation Test | 3 mo | Measure of spatial neglect where patients must cross out lines placed in a random orientation. Missed lines may indicate areas of spatial neglect. |
| Geriatric Depression Scale Short Form | 3 mo | Measure of depression done as a self-report. It is a series of 15 questions designed to be a screen for depression. The scores range from 0-15 with a higher score being more indicative of depression. |
| NIH Stroke Scale | 3 mo | Measure of global impairment post stroke. It includes 11 items to examine levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. The scoring scale is between 0-42 where a higher score is indicative of a more severe stroke. |
| Infarct Volume Using Anatomical MRI | 3 mo | Measurement of infarct volume and percent change from baseline to Day 90. |
| Trail Making A Test | 3 mo | Measure of memory and executive function where one is asked to connect dots consecutively based on the number of the dot. Test taker is allowed 2 minutes to connect the dots with a maximum score of 25 for all dots connected correctly. |
| Trail Making B Test | 3 mo. | Measure of memory and executive function where one is asked to connect dots with letters and numbers alternating between number and letter and connecting dots consecutively. Test taker is allowed 4 minutes to connect the dots with a maximum score of 25 for all dots connected correctly. |
| Barthel Index | 3 mo | Measure of disability in terms of performance of activities of daily living (ADL). The scores range from 0-100 with a higher score being associated with a higher level of independence. |
| Action Research Arm Test | 3 mo | The Action Research Arm Test is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale ranging from: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. Total scores range from 0-57 points, a higher score being better with 57 being considered normal. |
| Fugl-Meyer Arm Scale | 3 mo | Fugl-Meyer arm scale is a measurement scale of the upper body with three sections being Proximal, Wrist/Hand, and Coordination/Speed. The scores can range from 0-66 with a higher score being better. A score of 66 is considered normal with no impairments. |
Countries
United States
Participant flow
Recruitment details
Subjects were consented and enrolled from September 2006 to February 2008 in accordance with local Institutional Review Boards at 3 North American sites: University of California Irvine Medical Center (n=11), Hoag Memorial Hospital Presbyterian (n=1), and the Foothills Hospital at University of Calgary (n=3).
Participants by arm
| Arm | Count |
|---|---|
| Beta-hCG + Erythropoietin Subjects received a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation) | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Beta-hCG + Erythropoietin |
|---|---|
| Age, Continuous | 72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of Atrial Fibrillation No | 11 participants |
| History of Atrial Fibrillation Yes | 4 participants |
| History of Diabetes Mellitus No | 9 participants |
| History of Diabetes Mellitus Yes | 6 participants |
| History of Hyperlipidemia No | 6 participants |
| History of Hyperlipidemia Yes | 9 participants |
| History of Hypertension No | 3 participants |
| History of Hypertension Yes | 12 participants |
| History of Prior Stroke No | 10 participants |
| History of Prior Stroke Yes | 5 participants |
| Region of Enrollment Canada | 3 participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 6 / 15 |
Outcome results
Primary
Morbidity
attributable to experimental intervention
Time frame: 3 mo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dual Growth Factor | Morbidity | 0 participants |
Primary
Mortality
attributable to experimental intervention
Time frame: 3 mo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dual Growth Factor | Mortality | 0 participants |
Primary
Safety
Safety through Day 90 was assessed through adverse event reporting, serial examinations, blood testing, and a leg vein Doppler at Day 42. Number of participants who experienced adverse events, had abnormality in serial examinations, blood testing, and a leg vein Doppler at Day 42.
Time frame: 3 mo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dual Growth Factor | Safety | 0 participants |
Secondary
Action Research Arm Test
The Action Research Arm Test is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale ranging from: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. Total scores range from 0-57 points, a higher score being better with 57 being considered normal.
Time frame: 3 mo
Population: This number (9) is the total # subjects who could complete the test at all study time points; some subjects were unable to complete this test at one of the time points, especially the acute stroke assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Action Research Arm Test | 23 Units on a scale |
Secondary
Barthel Index
Measure of disability in terms of performance of activities of daily living (ADL). The scores range from 0-100 with a higher score being associated with a higher level of independence.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Barthel Index | 25 Units on a scale |
Secondary
Boston Naming Test
Measure of aphasia or other language disturbance caused by stroke or other dementing disorders. It consists of 60 line drawings graded in difficulty in which patients are to name each picture.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Boston Naming Test | 2 Units on a scale |
Secondary
Fugl-Meyer Arm Scale
Fugl-Meyer arm scale is a measurement scale of the upper body with three sections being Proximal, Wrist/Hand, and Coordination/Speed. The scores can range from 0-66 with a higher score being better. A score of 66 is considered normal with no impairments.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Fugl-Meyer Arm Scale | 32 Units on a scale |
Secondary
Fugl-Meyer Leg Scale
Measure of leg motor impairment with three subsections which are Proximal, Hip/Knee, and Speed/Coordination. The scale ranges from 0-34 with a higher score being better. A score of 34 is considered normal.
Time frame: 3 mo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Fugl-Meyer Leg Scale | 20 Units on a scale |
Secondary
Geriatric Depression Scale Short Form
Measure of depression done as a self-report. It is a series of 15 questions designed to be a screen for depression. The scores range from 0-15 with a higher score being more indicative of depression.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Geriatric Depression Scale Short Form | 5 Units on a scale |
Secondary
Infarct Volume Using Anatomical MRI
Measurement of infarct volume and percent change from baseline to Day 90.
Time frame: 3 mo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dual Growth Factor | Infarct Volume Using Anatomical MRI | -22 percent change | Standard Error 34 |
Secondary
Line Cancellation Test
Measure of spatial neglect where patients must cross out lines placed in a random orientation. Missed lines may indicate areas of spatial neglect.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Line Cancellation Test | 96 ratio of canceled lines on each side |
Secondary
NIH Stroke Scale
Measure of global impairment post stroke. It includes 11 items to examine levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. The scoring scale is between 0-42 where a higher score is indicative of a more severe stroke.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | NIH Stroke Scale | 10 Units on a scale |
Secondary
Trail Making A Test
Measure of memory and executive function where one is asked to connect dots consecutively based on the number of the dot. Test taker is allowed 2 minutes to connect the dots with a maximum score of 25 for all dots connected correctly.
Time frame: 3 mo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Trail Making A Test | 8 correct connections |
Secondary
Trail Making B Test
Measure of memory and executive function where one is asked to connect dots with letters and numbers alternating between number and letter and connecting dots consecutively. Test taker is allowed 4 minutes to connect the dots with a maximum score of 25 for all dots connected correctly.
Time frame: 3 mo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dual Growth Factor | Trail Making B Test | 3 correct connections |