Back to resultsStudy of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke (MINOS)
Primary Purpose
Stroke, Acute
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Minocycline
Sponsored by
About this trial
This is an interventional treatment trial for Stroke, Acute focused on measuring stroke, ischemic, neuroprotection, minocycline, tissue plasminogen activator (tPA), biomarkers, pharmacokinetics, antiapoptotic, anti-inflammatory, treatment, matrix metalloproteinase-9 (MMP-9), thrombolysis, Minocycline to Improve Neurologic Outcome in Stroke (MINOS), cerebrovascular stroke, cerebrovascular accident, cerebral stroke, cerebrovascular accident (CVA)
Eligibility Criteria
Inclusion Criteria:
- over 18 years of age
- acute onset focal neurologic deficit consistent with acute ischemic stroke, or computed tomographic scan consistent with acute cerebral ischemia
- onset of symptoms less than 6 hours
- measurable neurologic deficit (National Institutes of Health [NIH] Stroke Scale >/= 1)
Exclusion Criteria:
- allergy to tetracycline antibiotics
- women of child-bearing potential
- known hepatic and/or renal insufficiency
- Thrombocytopenia
- history of intolerance to minocycline
- dizziness at the time of stroke or in the past month (by self-report)
- aphasia likely to interfere with patients ability to report adverse effects
- previous functional disability
- stuporous or comatose
- presence of another serious illness likely to confound the study
- unlikely to be available for 90 day follow-up
- severe stroke (National Institutes of Health [NIH] Stroke Scale >22)
- undergoing an interventional neuro-radiological intervention in first 12 hour
Sites / Locations
- University of Kentucky
- Oregon Health & Science University
Outcomes
Primary Outcome Measures
Maximally Tolerated Dose of IV Minocycline
Investigators closely monitored each subject for evidence of minocycline intolerance. All adverse events were immediately reported for a decision whether to discontinue the study medication and/or reduce the dose. A computer program was used to determine the maximum tolerated dose. After entering information regarding doses and expected toxicities, results for each subject as they were collected were entered. The computer program informed as to (de)escalation, or maintenance of the same dose in the subsequent cohort of enrolled patients.
Secondary Outcome Measures
Half-life of IV Minocycline
In eligible patients enrolled at Georgia Health Sciences University, blood samples were drawn for quantification of minocycline serum concentrations. This enabled the study team to determine the half life of the study drug.
90 Day Modified Rankin Scale Score
The modified Rankin Scale (mRS) was performed in person at the 90 day clinic follow-up appointment. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6. 0 represents no symptoms. 1 represents no significant disability. 2 represents slight disability. 3 represents moderate disability. 4 represents moderately severe disability. 5 represents severe disability. 6 represents death.
Full Information
NCT ID
NCT00630396
First Posted
February 28, 2008
Last Updated
December 9, 2011
Sponsor
David Hess, MD
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of Kentucky, Oregon Health and Science University
1. Study Identification
Unique Protocol Identification Number
NCT00630396
Brief Title
Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke
Acronym
MINOS
Official Title
Minocycline to Improve Neurologic Outcome in Stroke (MINOS)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David Hess, MD
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of Kentucky, Oregon Health and Science University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary aim of this study is to find out which of 4 different doses of minocycline are safe and well tolerated so that we will know the optimal dose to test in future patients.
Detailed Description
Minocycline is a widely used antibiotic and is approved by the Food and Drug Administration (FDA) for treatment of infections and acne. However, doctors do not know whether minocycline will work in stroke patients. Its use in stroke patients is experimental. There is a lot of information from experimental stroke studies in animals that minocycline lessens the damage from a stroke and the animals recover better. Since minocycline is generally a very safe drug in humans and does not have a lot of side effects, investigators at Georgia Health Sciences University (formerly the Medical College of Georgia) believe that it might be a safe and effective drug to improve the outcome in patients with stroke.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Acute
Keywords
stroke, ischemic, neuroprotection, minocycline, tissue plasminogen activator (tPA), biomarkers, pharmacokinetics, antiapoptotic, anti-inflammatory, treatment, matrix metalloproteinase-9 (MMP-9), thrombolysis, Minocycline to Improve Neurologic Outcome in Stroke (MINOS), cerebrovascular stroke, cerebrovascular accident, cerebral stroke, cerebrovascular accident (CVA)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Minomycin, Minocycline hydrochloride, Minocycline hydrochloride injection, Minomycin Intravenous (for drip use), Minomycin Intravenous, MINO
Intervention Description
Dose level 1 = 3mg/kg intravenous (IV) initial dose, followed by 1.5mg/kg every 12 hours times 5 more doses.
Dose level 2 = 4.5mg/kg intravenous (IV) initial dose, followed by 2.25mg/kg every 12 hours times 5 more doses.
Dose level 3 = 6 mg/kg intravenous (IV) initial dose, followed by 3 mg/kg every 12 hours times 5 more doses.
Dose level 4 = 10 mg/kg intravenous (IV) initial dose, followed by 5 mg/kg every 12 hours times 5 more doses
Primary Outcome Measure Information:
Title
Maximally Tolerated Dose of IV Minocycline
Description
Investigators closely monitored each subject for evidence of minocycline intolerance. All adverse events were immediately reported for a decision whether to discontinue the study medication and/or reduce the dose. A computer program was used to determine the maximum tolerated dose. After entering information regarding doses and expected toxicities, results for each subject as they were collected were entered. The computer program informed as to (de)escalation, or maintenance of the same dose in the subsequent cohort of enrolled patients.
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Half-life of IV Minocycline
Description
In eligible patients enrolled at Georgia Health Sciences University, blood samples were drawn for quantification of minocycline serum concentrations. This enabled the study team to determine the half life of the study drug.
Time Frame
For each subject blood samples were drawn before dose #1 and one hour after starting dose #1. Additional blood was drawn 1, 6, 12, 24, 48, and 72 hours after starting dose #6, which lasted approximately 6 days.
Title
90 Day Modified Rankin Scale Score
Description
The modified Rankin Scale (mRS) was performed in person at the 90 day clinic follow-up appointment. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6. 0 represents no symptoms. 1 represents no significant disability. 2 represents slight disability. 3 represents moderate disability. 4 represents moderately severe disability. 5 represents severe disability. 6 represents death.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
over 18 years of age
acute onset focal neurologic deficit consistent with acute ischemic stroke, or computed tomographic scan consistent with acute cerebral ischemia
onset of symptoms less than 6 hours
measurable neurologic deficit (National Institutes of Health [NIH] Stroke Scale >/= 1)
Exclusion Criteria:
allergy to tetracycline antibiotics
women of child-bearing potential
known hepatic and/or renal insufficiency
Thrombocytopenia
history of intolerance to minocycline
dizziness at the time of stroke or in the past month (by self-report)
aphasia likely to interfere with patients ability to report adverse effects
previous functional disability
stuporous or comatose
presence of another serious illness likely to confound the study
unlikely to be available for 90 day follow-up
severe stroke (National Institutes of Health [NIH] Stroke Scale >22)
undergoing an interventional neuro-radiological intervention in first 12 hour
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David C Hess, MD
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40506-0057
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20705929
Citation
Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, Hall CE, Switzer JA, Ergul A, Hess DC. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010 Oct;41(10):2283-7. doi: 10.1161/STROKEAHA.110.582601. Epub 2010 Aug 12.
Results Reference
result
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Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke
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