Beta-hCG + Erythropoietin in Acute Stroke (BETAS)

• ClinicalTrials.gov Identifier: NCT00362414
• Recruitment Status: Completed
• First Posted: August 10, 2006
• Results First Posted: August 29, 2016
• Last Update Posted: August 29, 2016
• Sponsor: University of California, Irvine
• Collaborators: Stem Cell Therapeutics Corp.; Hoag Memorial Hospital Presbyterian
• Information provided by (Responsible Party): Steven C. Cramer, MD, University of California, Irvine

Study Description

Brief Summary:

The purpose of this study is to assess the safety of Beta-hCG + Erythropoietin in patients with acute ischemic stroke.

Condition or disease	Intervention/treatment	Phase
Acute Stroke	Drug: Dual Growth Factor	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Beta-hCG + Erythropoietin in Acute Stroke
• Study Start Date: August 2006
• Actual Primary Completion Date: March 2008
• Actual Study Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dual Growth Factor; All patients received erythropoietin and beta-hCG. This was the only treatment arm in the study, i.e., all enrollees received active therapy.	Drug: Dual 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

Outcome Measures

Primary Outcome Measures :

1. Safety [ Time Frame: 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.
2. Morbidity [ Time Frame: 3 mo ]
   attributable to experimental intervention
3. Mortality [ Time Frame: 3 mo ]
   attributable to experimental intervention

Secondary Outcome Measures :

1. Action Research Arm Test [ Time Frame: 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".
2. Fugl-Meyer Arm Scale [ Time Frame: 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.
3. Fugl-Meyer Leg Scale [ Time Frame: 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".
4. Boston Naming Test [ Time Frame: 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.
5. Line Cancellation Test [ Time Frame: 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.
6. NIH Stroke Scale [ Time Frame: 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.
7. Geriatric Depression Scale Short Form [ Time Frame: 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.
8. Barthel Index [ Time Frame: 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.
9. Infarct Volume Using Anatomical MRI [ Time Frame: 3 mo ]
   Measurement of infarct volume and percent change from baseline to Day 90.
10. Trail Making A Test [ Time Frame: 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.
11. Trail Making B Test [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, Irvine Medical Center

Orange, California, United States, 92868-4280

Sponsors and Collaborators

University of California, Irvine

Stem Cell Therapeutics Corp.

Hoag Memorial Hospital Presbyterian

Investigators

• Principal Investigator: Steven C. Cramer, MD, MMSc; University of California, Irvine

More Information

• Responsible Party: Steven C. Cramer, MD, Professor, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT00362414
• Other Study ID Numbers: HS#2005-4800
• First Posted: August 10, 2006
• Results First Posted: August 29, 2016
• Last Update Posted: August 29, 2016
• Last Verified: August 2016

Keywords provided by Steven C. Cramer, MD, University of California, Irvine:

Stroke

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mitogens; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action