NCT00630396

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2008

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 28, 2008

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 7, 2008

Completed
2 months until next milestone

Study Start

First participant enrolled

May 1, 2008

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2010

Completed
2 years until next milestone

Results Posted

Study results publicly available

January 13, 2012

Completed
Last Updated

January 13, 2012

Status Verified

December 1, 2011

Enrollment Period

1.7 years

First QC Date

February 28, 2008

Results QC Date

August 1, 2011

Last Update Submit

December 9, 2011

Conditions

Keywords

strokeischemicneuroprotectionminocyclinetissue plasminogen activator (tPA)biomarkerspharmacokineticsantiapoptoticanti-inflammatorytreatmentmatrix metalloproteinase-9 (MMP-9)thrombolysisMinocycline to Improve Neurologic Outcome in Stroke (MINOS)cerebrovascular strokecerebrovascular accidentcerebral strokecerebrovascular accident (CVA)

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (2)

  • Half-life of IV Minocycline

    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.

  • 90 Day Modified Rankin Scale Score

    3 months

Interventions

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

Also known as: Minomycin, Minocycline hydrochloride, Minocycline hydrochloride injection, Minomycin Intravenous (for drip use), Minomycin Intravenous, MINO

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40506-0057, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related 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.110.582601. Epub 2010 Aug 12.

MeSH Terms

Conditions

StrokeIschemiacyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Limitations and Caveats

Some statistical tests could not be performed due to small sample size in the 4.5 and 6mg/kg dose tiers. The modified continual reassessment method (CRM) failed to identify the maximum tolerated dose of intravenous minocycline.

Results Point of Contact

Title
David Hess, MD
Organization
Georgia Health Sciences University

Study Officials

  • David C Hess, MD

    Augusta University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor and Chairman

Study Record Dates

First Submitted

February 28, 2008

First Posted

March 7, 2008

Study Start

May 1, 2008

Primary Completion

January 1, 2010

Study Completion

January 1, 2010

Last Updated

January 13, 2012

Results First Posted

January 13, 2012

Record last verified: 2011-12

Locations