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Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke

Phase 1
Completed
Conditions
Stroke, Acute
Registration Number
NCT00630396
Lead Sponsor
David Hess, MD
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Maximally Tolerated Dose of IV Minocycline3 days

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
NameTimeMethod
Half-life of IV MinocyclineFor 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.

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 Score3 months

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.

Trial Locations

Locations (2)

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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