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

This study has been completed.
Sponsor:
Collaborators:
University of Kentucky
Oregon Health and Science University
Information provided by (Responsible Party):
David Hess, MD, Georgia Health Sciences University
ClinicalTrials.gov Identifier:
NCT00630396
First received: February 28, 2008
Last updated: December 9, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Stroke, Acute
Drug: Minocycline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Minocycline to Improve Neurologic Outcome in Stroke (MINOS)

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Maximally Tolerated Dose of IV Minocycline [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    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 [ 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 60
Study Start Date: May 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Minocycline

    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

    Other Names:
    • Minomycin
    • Minocycline hydrochloride
    • Minocycline hydrochloride injection
    • Minomycin Intravenous (for drip use)
    • Minomycin Intravenous
    • MINO
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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00630396

Locations
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40506-0057
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
David Hess, MD
University of Kentucky
Oregon Health and Science University
Investigators
Principal Investigator: David C Hess, MD Georgia Regents University
  More Information

Publications:
Responsible Party: David Hess, MD, Professor and Chairman, Georgia Health Sciences University
ClinicalTrials.gov Identifier: NCT00630396     History of Changes
Other Study ID Numbers: RO1 NS055728-01A1, 07-02-202
Study First Received: February 28, 2008
Results First Received: August 1, 2011
Last Updated: December 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgia Regents University:
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)

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Minocycline
Tissue Plasminogen Activator
Neuroprotective Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Protective Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 16, 2014