Stroke, AcutePhase 1/2MINOSNCT00630396

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

A Phase 1/2 study testing Minocycline in people with Stroke, Acute, run by David Hess, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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. Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Stroke, Acute
What is being tested?: Minocycline
Type of treatment: Injection or infusion
How many people: 60 participants
Where: 2 sitesUnited States
Study dates: May 2008to Jan 2010
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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)

Show all 13Show fewer

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Kentucky
Lexington, Kentucky, 40506-0057
Oregon Health & Science University
Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Minocycline to Improve Neurologic Outcome in Stroke (MINOS)

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.

Read the 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.

Conditions: Stroke, Acute
Being tested: Minocycline
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)
Medical subject headings: Stroke, Ischemia, cyclopia sequence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MinocyclineDrug
Also called Minomycin, Minocycline hydrochloride, Minocycline hydrochloride injection, Minomycin Intravenous (for drip use)
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

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 days

Secondary outcomes (2)

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.
Measured: 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
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.
Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Jan 2010

First posted7 Mar 2008 (estimated)
Study startMay 2008
Primary completionJan 2010
Study completionJan 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Stroke, AcuteStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00630396
Sponsor's protocol ID: R01NS055728-01A1
Other IDs: 07-02-202
Acronym: MINOS
Status last verified: Dec 2011
First submitted: 28 Feb 2008
Last updated: 13 Jan 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 20705929

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Stroke, Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Minocycline to Improve Neurologic Outcome in Stroke (MINOS)
ClinicalTrials.gov ID: NCT00630396
Acronym / sponsor ID: MINOS / R01NS055728-01A1
Conditions: Stroke, Acute
Keywords: stroke, ischemic, neuroprotection, minocycline, tissue plasminogen activator (tPA), biomarkers, pharmacokinetics, antiapoptotic
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: David Hess, MDUniversity, hospital or other
Collaborators: National Institute of Neurological Disorders and Stroke (NINDS), University of Kentucky, Oregon Health and Science University
Study start: May 2008
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 7 Mar 2008 (estimated)
Results: Posted 13 Jan 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (13 listed)

allergy to tetracycline antibiotics
women of child-bearing potential
known hepatic and/or renal insufficiency
Thrombocytopenia
history of intolerance to minocycline

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MinocyclineAlso: Minomycin, Minocycline hydrochloride, Minocycline hydrochloride injection, Minomycin Intravenous (for drip use)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	Drug	–

Primary outcome

Maximally Tolerated Dose of IV Minocycline
Time frame: 3 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.

2 secondary outcomes

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.
90 Day Modified Rankin Scale Score
Time frame: 3 months

Results and safety

Results posted to the registry on 13 Jan 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocycline	60	53

Primary outcome: Maximally Tolerated Dose of IV Minocycline

Time frame: 3 days. Number. Unit: mg/kg

Measure	Minocycline n = 60
Value	10

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected for one year and seven months. This time period started when the first subject was enrolled and lasted until the 90 day follow-up was completed for the last subject enrolled.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocycline	29 of 60 (48.3%)	50 of 60 (83.3%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 20705929Fagan 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.

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RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
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Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David C Hess, MD principal investigator

Augusta University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Minocycline in people with Stroke, Acute, run by David Hess, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximally Tolerated Dose of IV Minocycline (time frame: 3 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00630396, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2012.