Cerebrovascular AccidentPhase 1NCT00097318
Safety Study of Interferon Beta 1a to for Acute Stroke
A Phase 1 study testing Interferon beta-1a in people with Cerebrovascular Accident, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in United States.
Trial summary
This study will examine the safety of the drug interferon beta 1a in patients with acute ischemic stroke to determine the highest dose patients can tolerate without serious side effects and to determine the best way to give the medication. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Cerebrovascular Accident
- What is being tested?
- Interferon beta-1a
- How many people
- 60 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Nov 2004to 8 Apr 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female patients with confirmed acute ischemic stroke, presenting within 24 hours of symptom onset and meeting inclusion criteria at each of the study sites will be assessed for possible enrollment into the study.
- New focal neurologic deficit consistent with acute cerebral ischemia.
- Age greater than or equal to 18 and less than or equal to 85.
- Premorbid modified Rankin score 0-2 (functionally independent).
- Signed informed consent obtained from the patient or patient's legally authorized representative.
- Initiation of study drug within 24 hours of symptom onset.
Who cannot join
- Acute intracerebral hemorrhage.
- Major surgery planned within 30 days of symptom onset.
- Treatment with IV tPA or other recanalization therapy for current event.
- Pre-existing medical, neurological or psychiatric disease that would confound the outcome evaluations.
- Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
- Coma or altered level of consciousness (score of 1 or more on LOC items of NIHSS score).
Show all 17Show fewer
- Hemodynamic instability.
- Current participation in another experimental treatment protocol.
- Inadequate liver function, defined by a total bilirubin, AST or ALT or alkaline phosphatase greater than 2 times the upper limit of normal values.
- Renal impairment with serum creatinine greater than 2.0 mg/dl.
- NIHSS greater than 18.
- Prior use of interferon.
- Active major infection.
- Allergy to human serum albumin, mannitol.
- Seizure disorder or seizure at onset of stroke.
- Severe depressive disorder and/or suicidal ideation.
- Significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal) within 7 days prior to symptom onset.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Suburban Hospital
Bethesda, Maryland, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Recombinant Human Interferon Beta-1a in Acute Ischemic Stroke: A Dose Escalation and Safety Study
This study will examine the safety of the drug interferon beta 1a in patients with acute ischemic stroke to determine the highest dose patients can tolerate without serious side effects and to determine the best way to give the medication. Ischemic stroke is caused by a blood clot blocking the flow of blood to brain tissue, causing loss or impairment of bodily functions governed by the affected part of the brain. Interferon beta 1a is approved for use in patients with multiple sclerosis to prevent further brain injury caused by inflammation; the drug may also help prevent further brain injury in patients with acute stroke.
Patients between 18 and 85 years of age who have had a stroke and who can begin taking the study drug within 24 hours of onset of stroke symptoms may be eligible for this study. Candidates are screened with a medical history, physical examination and neurological examinations, blood tests, electrocardiogram, and brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) scans.
Read more
Participants are randomly assigned to receive either interferon beta 1a or placebo (an inactive substance). For every five patients enrolled, four receive the study drug and one receives placebo. The dose of interferon beta 1a is increased in successive groups of patients, so that the first group to enter the study receives 11 micrograms (mcg) of the drug, the next receives 22 mcg, then 44 mcg, 66 mcg, and 88 mcg. All patients receive their first dose intravenously (through a vein); additional doses are given subcutaneously (under the skin).
During their hospital stay all participants receive standard medical care for stroke, have neurological checks every 6 hours, and have continuous heart monitoring. To prevent fever, they receive medication, such as Tylenol, before each dose of interferon beta 1a or placebo and every 6 hours as needed while taking the study drug. Routine blood tests are done at 3 and 7 days after the first dose of study drug (or at discharge if the patient leaves the hospital before 7 days) and again at 14, 21, and 28 days. Neurological examinations are done 24 hours after starting the study medication, then every day for 14 days, and again on day 28.
After discharge from the hospital, patients are seen by a nurse every day foan 14 days after the first medication dose. They are contacted by phone on days 17 and 21. On day 28 they return to the hospital as an outpatient for a neurological assessment and blood tests.
Read the detailed description
Objectives: Recombinant human interferon beta-1a (IFN-Beta1a) is an FDA approved treatment for patients with relapsing remitting multiple sclerosis, in whom the safety profile is well characterized. The actions of IFN-Beta1a to inhibit pro-inflammatory cytokines and prevent blood brain barrier disruption suggest a therapeutic potential in ischemic stroke, and recent experimental evidence supports that effect. This study will be the first clinical trial exposure of patients with acute stroke to IFN-Beta1a. The purpose of this study is to investigate the safety of IFN-Beta1a (Rebif(Registered Trademark)) in patients with acute ischemic stroke.
Study Population: Patients age 18-85 years with probable or definite acute ischemic cerebrovascular syndrome within 24 hours of onset will be studied.
Design: This is a randomized double-blind placebo-controlled sequential dose escalation, phase 1 trial. Five dose cohorts of 5 patients (4:1 active: placebo) will be studied at 11 mcg, 22 mcg, 44 mcg, 66 mcg and 88 mcg administered daily for 7 days. The first dose will be administered intravenously and subsequent doses will be administered subcutaneously. Patients will be pre-medicated to prevent fevers, a common complication of interferon treatment, since fever may worsen stroke outcome. Patients will be monitored for adverse events and neurological outcomes up to 28 days from onset of treatment. Data will be reviewed in an ongoing fashion by a data safety monitoring board (DSMB). Dose escalation will be continuous unless drug-related toxicity reaches a predetermined level of one dose-limiting adverse event (1 of 4 treated) within a dose cohort, in which case a second cohort of 5 patients (4:1) will be treated at that dose. The study will be terminated at a dose level at which 2 of 4 or 3 of 8 patients on active treatment have a severe dose limiting toxicity or when all planned dose cohorts have been completed.
Outcome Measures: Expected, common toxicities with IFN-Beta1a treatment are flu-like symptoms (e.g., fevers, myalgias, headaches, fatigue) and injection site reactions. With long term administration liver function abnormalities and leukopenia may occur and these will also be monitored. Toxicity will be graded according to the NCI criteria as well as study specific criteria defined in section 7a. Dose limiting toxicities will be considered any serious adverse event or grade 3 toxicity judged to be probably or definitely related to study medication or grade 4 or 5 toxicity judged to be possibly, probably or definitely related to study medication or any of the predefined study specific criteria. Serum levels of IFN-Beta1a and serum markers of IFN-Beta1a activity will be measured to characterize the pharmacokinetics and pharmacodynamics of IFN-Beta 1a in acute stroke patients.
- Conditions
- Cerebrovascular Accident
- Being tested
- Interferon beta-1a
- Keywords
- Ischemic, Brain, Inflammation, Clinical Trial, Stroke
- Medical subject headings
- Stroke, Ischemia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon beta-1aDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2004 (estimated)
- Study start17 Nov 2004
- Study completion8 Apr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular AccidentStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00097318
- Sponsor's protocol ID
- 050036
- Other IDs
- 05-N-0036
- Status last verified
- 8 Apr 2011
- First submitted
- 20 Nov 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Hallenbeck JM, Dutka AJ. Background review and current concepts of reperfusion injury. Arch Neurol. 1990 Nov;47(11):1245-54. doi: 10.1001/archneur.1990.00530110107027.
PubMed 2241624Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke. 1992 Sep;23(9):1367-79. doi: 10.1161/01.str.23.9.1367.
PubMed 1519296Feuerstein GZ, Wang X, Barone FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation. 1998 May-Aug;5(3-4):143-59. doi: 10.1159/000026331.
PubMed 9730680
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recombinant Human Interferon Beta-1a in Acute Ischemic Stroke: A Dose Escalation and Safety Study
- ClinicalTrials.gov ID
- NCT00097318
- Acronym / sponsor ID
- 050036
- Conditions
- Cerebrovascular Accident
- Keywords
- Ischemic, Brain, Inflammation, Clinical Trial, Stroke
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 17 Nov 2004
- Study completion
- 8 Apr 2011 (actual)
- First posted
- 22 Nov 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety of the drug interferon beta 1a in patients with acute ischemic stroke to determine the highest dose patients can tolerate without serious side effects and to determine the best way to give the medication. Ischemic stroke is caused by a blood clot blocking the flow of blood to brain tissue, causing loss or impairment of bodily functions governed by the affected part of the brain. Interferon beta 1a is approved for use in patients with multiple sclerosis to prevent further brain injury caused by inflammation; the drug may also help prevent further brain injury in patients with acute stroke.
Patients between 18 and 85 years of age who have had a stroke and who can begin taking the study drug within 24 hours of onset of stroke symptoms may be eligible for this study. Candidates are screened with a medical history, physical examination and neurological examinations, blood tests, electrocardiogram, and brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) scans.
Participants are randomly assigned to receive either interferon beta 1a or placebo (an inactive substance). For every five patients enrolled, four receive the study drug and one receives placebo. The dose of interferon beta 1a is increased in successive groups of patients, so that the first group to enter the study receives 11 micrograms (mcg) of the drug, the next receives 22 mcg, then 44 mcg, 66 mcg, and 88 mcg. All patients receive their first dose intravenously (through a vein); additional doses are given subcutaneously (under the skin).
During their hospital stay all participants receive standard medical care for stroke, have neurological checks every 6 hours, and have continuous heart monitoring. To prevent fever, they receive medication, such as Tylenol, before each dose of interferon beta 1a or placebo and every 6 hours as needed while taking the study drug. Routine blood tests are done at 3 and 7 days after the first dose of study drug (or at discharge if the patient leaves the hospital before 7 days) and again at 14, 21, and 28 days. Neurological examinations are done 24 hours after starting the study medication, then every day for 14 days, and again on day 28.
After discharge from the hospital, patients are seen by a nurse every day foan 14 days after the first medication dose. They are contacted by phone on days 17 and 21. On day 28 they return to the hospital as an outpatient for a neurological assessment and blood tests.
Detailed description
Objectives: Recombinant human interferon beta-1a (IFN-Beta1a) is an FDA approved treatment for patients with relapsing remitting multiple sclerosis, in whom the safety profile is well characterized. The actions of IFN-Beta1a to inhibit pro-inflammatory cytokines and prevent blood brain barrier disruption suggest a therapeutic potential in ischemic stroke, and recent experimental evidence supports that effect. This study will be the first clinical trial exposure of patients with acute stroke to IFN-Beta1a. The purpose of this study is to investigate the safety of IFN-Beta1a (Rebif(Registered Trademark)) in patients with acute ischemic stroke.
Study Population: Patients age 18-85 years with probable or definite acute ischemic cerebrovascular syndrome within 24 hours of onset will be studied.
Design: This is a randomized double-blind placebo-controlled sequential dose escalation, phase 1 trial. Five dose cohorts of 5 patients (4:1 active: placebo) will be studied at 11 mcg, 22 mcg, 44 mcg, 66 mcg and 88 mcg administered daily for 7 days. The first dose will be administered intravenously and subsequent doses will be administered subcutaneously. Patients will be pre-medicated to prevent fevers, a common complication of interferon treatment, since fever may worsen stroke outcome. Patients will be monitored for adverse events and neurological outcomes up to 28 days from onset of treatment. Data will be reviewed in an ongoing fashion by a data safety monitoring board (DSMB). Dose escalation will be continuous unless drug-related toxicity reaches a predetermined level of one dose-limiting adverse event (1 of 4 treated) within a dose cohort, in which case a second cohort of 5 patients (4:1) will be treated at that dose. The study will be terminated at a dose level at which 2 of 4 or 3 of 8 patients on active treatment have a severe dose limiting toxicity or when all planned dose cohorts have been completed.
Outcome Measures: Expected, common toxicities with IFN-Beta1a treatment are flu-like symptoms (e.g., fevers, myalgias, headaches, fatigue) and injection site reactions. With long term administration liver function abnormalities and leukopenia may occur and these will also be monitored. Toxicity will be graded according to the NCI criteria as well as study specific criteria defined in section 7a. Dose limiting toxicities will be considered any serious adverse event or grade 3 toxicity judged to be probably or definitely related to study medication or grade 4 or 5 toxicity judged to be possibly, probably or definitely related to study medication or any of the predefined study specific criteria. Serum levels of IFN-Beta1a and serum markers of IFN-Beta1a activity will be measured to characterize the pharmacokinetics and pharmacodynamics of IFN-Beta 1a in acute stroke patients.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult male or female patients with confirmed acute ischemic stroke, presenting within 24 hours of symptom onset and meeting inclusion criteria at each of the study sites will be assessed for possible enrollment into the study.
- New focal neurologic deficit consistent with acute cerebral ischemia.
- Age greater than or equal to 18 and less than or equal to 85.
- Premorbid modified Rankin score 0-2 (functionally independent).
- Signed informed consent obtained from the patient or patient's legally authorized representative.
Key exclusion criteria (17 listed)
- Acute intracerebral hemorrhage.
- Major surgery planned within 30 days of symptom onset.
- Treatment with IV tPA or other recanalization therapy for current event.
- Pre-existing medical, neurological or psychiatric disease that would confound the outcome evaluations.
- Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon beta-1a | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 2241624Hallenbeck JM, Dutka AJ. Background review and current concepts of reperfusion injury. Arch Neurol. 1990 Nov;47(11):1245-54. doi: 10.1001/archneur.1990.00530110107027.
- Background: PubMed 1519296Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke. 1992 Sep;23(9):1367-79. doi: 10.1161/01.str.23.9.1367.
- Background: PubMed 9730680Feuerstein GZ, Wang X, Barone FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation. 1998 May-Aug;5(3-4):143-59. doi: 10.1159/000026331.
Related trials for Cerebrovascular Accident
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Interferon beta-1a in people with Cerebrovascular Accident, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00097318, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.