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

Stroke, Acute Clinical Trial

— MINOS  

Official title:

Minocycline to Improve Neurologic Outcome in Stroke (MINOS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00630396
• Other study ID #: RO1 NS055728-01A1
• Secondary ID: 07-02-202
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 28, 2008
• Last updated: December 9, 2011
• Start date: May 2008
• Est. completion date: January 2010

Study information

• Verified date: December 2011
• Source: Georgia Regents University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke
• Stroke, Acute

Intervention

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

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (4)

Lead Sponsor	Collaborator
David Hess, MD	National Institute of Neurological Disorders and Stroke (NINDS), Oregon Health and Science University, University of Kentucky

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.110.58260 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 days	Yes
Secondary	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.	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.	No
Secondary	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.	3 months	No