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Beta-hCG + Erythropoietin in Acute Stroke (BETAS)

Primary Purpose

Acute Stroke

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dual Growth Factor
Sponsored by
University of California, Irvine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Stroke focused on measuring Stroke

Eligibility Criteria

21 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 21-85 NIHSS score 6-24 at time of enrollment, ensuring that stroke is neither mild nor devastating Stroke is ischemic in origin, supratentorial, and radiologically confirmed 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. Reasonable expectation of availability to receive the full 9 day B-E therapy course Reasonable expectation that patient will receive standard post-stroke physical, occupational, speech, and cognitive therapy as indicated Exclusion Criteria: Pre-existing and active major psychiatric or other neurological disease History of significant alcohol or drug abuse in the prior 3 years 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 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 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. Contraindication to study participation on the basis of any of the following: Allergy or other contraindication to initiating either beta-hCG or Erythropoietin Known hypersensitivity to mammalian cell-derived products or hypersensitivity to albumin 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 Dysuria of unexplained origin Uncontrolled hypertension, defined in the context of acute stroke as blood pressure persistently above 220 mm Hg systolic or 120 diastolic despite antihypertensive therapy Current use of either beta-hCG or Erythropoietin Other condition known to elevate beta-hCG, active in the prior 24 months, e.g., choriocarcinoma or germ cell tumor Terminal medical diagnosis consistent with survival < 1 year 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.

Sites / Locations

  • University of California, Irvine Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dual Growth Factor

Arm Description

All patients received erythropoietin and beta-hCG. This was the only treatment arm in the study, i.e., all enrollees received active therapy.

Outcomes

Primary Outcome Measures

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.
Morbidity
attributable to experimental intervention
Mortality
attributable to experimental intervention

Secondary Outcome Measures

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".
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.
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".
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.
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.
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.
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.
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.
Infarct Volume Using Anatomical MRI
Measurement of infarct volume and percent change from baseline to Day 90.
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.
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.

Full Information

First Posted
August 9, 2006
Last Updated
August 16, 2016
Sponsor
University of California, Irvine
Collaborators
Stem Cell Therapeutics Corp., Hoag Memorial Hospital Presbyterian
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1. Study Identification

Unique Protocol Identification Number
NCT00362414
Brief Title
Beta-hCG + Erythropoietin in Acute Stroke
Acronym
BETAS
Official Title
Safety of Beta-hCG + Erythropoietin in Acute Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Irvine
Collaborators
Stem Cell Therapeutics Corp., Hoag Memorial Hospital Presbyterian

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Stroke
Keywords
Stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dual Growth Factor
Arm Type
Experimental
Arm Description
All patients received erythropoietin and beta-hCG. This was the only treatment arm in the study, i.e., all enrollees received active therapy.
Intervention Type
Drug
Intervention Name(s)
Dual Growth Factor
Intervention Description
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
Primary Outcome Measure Information:
Title
Safety
Description
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
Title
Morbidity
Description
attributable to experimental intervention
Time Frame
3 mo
Title
Mortality
Description
attributable to experimental intervention
Time Frame
3 mo
Secondary Outcome Measure Information:
Title
Action Research Arm Test
Description
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
Title
Fugl-Meyer Arm Scale
Description
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
Title
Fugl-Meyer Leg Scale
Description
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.
Title
Boston Naming Test
Description
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
Title
Line Cancellation Test
Description
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
Title
NIH Stroke Scale
Description
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
Title
Geriatric Depression Scale Short Form
Description
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
Title
Barthel Index
Description
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
Title
Infarct Volume Using Anatomical MRI
Description
Measurement of infarct volume and percent change from baseline to Day 90.
Time Frame
3 mo
Title
Trail Making A Test
Description
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
Title
Trail Making B Test
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 21-85 NIHSS score 6-24 at time of enrollment, ensuring that stroke is neither mild nor devastating Stroke is ischemic in origin, supratentorial, and radiologically confirmed 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. Reasonable expectation of availability to receive the full 9 day B-E therapy course Reasonable expectation that patient will receive standard post-stroke physical, occupational, speech, and cognitive therapy as indicated Exclusion Criteria: Pre-existing and active major psychiatric or other neurological disease History of significant alcohol or drug abuse in the prior 3 years 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 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 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. Contraindication to study participation on the basis of any of the following: Allergy or other contraindication to initiating either beta-hCG or Erythropoietin Known hypersensitivity to mammalian cell-derived products or hypersensitivity to albumin 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 Dysuria of unexplained origin Uncontrolled hypertension, defined in the context of acute stroke as blood pressure persistently above 220 mm Hg systolic or 120 diastolic despite antihypertensive therapy Current use of either beta-hCG or Erythropoietin Other condition known to elevate beta-hCG, active in the prior 24 months, e.g., choriocarcinoma or germ cell tumor Terminal medical diagnosis consistent with survival < 1 year 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven C. Cramer, MD, MMSc
Organizational Affiliation
University of California, Irvine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868-4280
Country
United States

12. IPD Sharing Statement

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Beta-hCG + Erythropoietin in Acute Stroke

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