Minocycline for Stroke

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Disqualifiers: Allergy to tetracycline, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Minocycline for stroke?

Research shows that Minocycline, an antibiotic, has potential neuroprotective effects in stroke patients. It has been found to reduce brain damage and improve outcomes in animal models and early human trials, making it a promising candidate for stroke treatment. ^{1 2 3 4 5}

What makes minocycline unique for treating stroke?

Minocycline is unique for stroke treatment because it is an antibiotic that also offers neuroprotective benefits, reducing brain cell damage and inflammation, which is not typical for standard stroke treatments. Unlike traditional therapies that focus on dissolving clots, minocycline targets multiple pathways to protect brain tissue and improve recovery. ^{1 2 3 6 7}

What is the purpose of this trial?

Previous work has demonstrated patients presenting with ruptured aneurysms that develop radiographic and clinical vasospasm have a higher permeability of the blood brain membrane. Matrix metalloproteinase 9 (MMP9) has been studied and recently implicated in both the pathogenesis of the blood brain barrier breakdown and vasogenic edema of ischemia strokes, and is suggested to be an accurate biomarker to predict the onset of cerebral vasospasm after subarachnoid hemorrhage. The therapeutic benefit of minocycline, an MMP9 inhibitor, has been investigated in ischemic stroke population, however its role in the treatment of cerebral vasospasm from ruptured aneurysms remains unknown. Our project has two main goals: to further confirm MMP9 has a reliable biomarker for the onset of cerebral vasospasm, and secondarily to investigate any possible therapeutic benefit that minocycline has in the vasospasm population. Vasospasm continues to be one of the major contributors of morbidity and mortality in the ruptured aneurysm population, and close monitoring of the neurologic exam during the 'vasospasm window' usually requires two weeks in the intensive care unit in most academic settings. As such, if we are better able to predict which patients are at risk of developing vasospasm based on MMP9 levels, we will be better able to anticipate the need for intervention and therefore mitigate the risk of vasospasm induced ischemic strokes, ultimately resulting in better outcomes in the ruptured aneurysm population. Further, if we are able to identify minocycline as a therapeutic agent to deter, or lessen the severity of vasospasm, we can possibly improve neurologic outcomes, decrease hospital stays, ultimately providing an improved and more cost-effective treatment strategy to our patients.

Eligibility Criteria

This trial is for adults aged 18 to 85 who have had a ruptured cerebral aneurysm and can start the trial within 24 hours of the rupture. It's not suitable for those allergic to tetracycline, pregnant individuals, or people with liver or kidney failure.

Inclusion Criteria

I have had a ruptured brain aneurysm.

I was enrolled in the study within a day of my rupture.

Exclusion Criteria

I have kidney failure.

My liver is not working properly.

You are allergic to tetracycline.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose intravenous Minocycline treatment to assess its effect on BBB permeability and serum MMP9 levels

2 weeks

Daily monitoring in the intensive care unit

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on clinical vasospasm and safety profile

4 weeks

Treatment Details

Interventions

• Minocycline

Trial Overview The MASH trial is testing whether minocycline, which inhibits MMP9 (a molecule involved in brain damage after bleeding), can predict and reduce complications from blood vessel spasms after a brain hemorrhage due to aneurysm rupture.

Minocycline is already approved in United States, European Union, Japan, India for the following indications:

Approved in United States as Minocin for:

• Acne
• Bacterial infections
• Periodontal disease
• Rosacea

Approved in European Union as Minostad for:

• Acne

Approved in Japan as Minopen for:

• Bacterial infections

Approved in India as Minoz for:

• Bacterial infections

Approved in United States as Amzeeq for:

• Acne

Approved in United States as Zilxi for:

• Rosacea

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Findings from Research

Minocycline, a tetracycline antibiotic, shows potential as a neuroprotective agent in acute ischemic stroke, demonstrating effects on reducing cell death, inflammation, and injury in both animal models and early human trials.

Current systemic thrombolytic therapies for stroke are limited by strict eligibility criteria and risks of bleeding, highlighting the need for alternative treatments like minocycline that may improve long-term outcomes without these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline repurposing in critical illness: focus on stroke. Liao, TV., Forehand, CC., Hess, DC., et al.[2021]

In a study of 50 acute ischemic stroke patients, those treated with oral minocycline showed significant improvements in clinical outcomes, including NIHSS, mRS, and Barthel Index scores at 30 and 90 days compared to the control group receiving vitamin B.

No serious adverse effects, such as mortality or recurrent strokes, were reported in either group, indicating that minocycline is a safe option for improving recovery after an acute ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial. Padma Srivastava, MV., Bhasin, A., Bhatia, R., et al.[2019]

In a study involving 16 patients with intracerebral hemorrhage, intravenous minocycline was found to be safe and maintained neuroprotective serum concentrations, indicating its potential as a treatment option.

However, the oral form of minocycline showed delayed absorption, taking at least 6 hours to reach peak concentration, which may limit its effectiveness in acute situations where rapid action is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. Fouda, AY., Newsome, AS., Spellicy, S., et al.[2019]

Minocycline, an antibiotic with neuroprotective properties, has shown promise in reducing brain damage and improving recovery in animal models of stroke, making it a strong candidate for treating acute ischemic stroke due to its ability to cross the blood-brain barrier and its good safety profile.

Early phase clinical trials indicate that minocycline is safe and may be effective in treating acute ischemic stroke, either alone or with other treatments, but further large-scale studies are necessary to confirm its efficacy and determine its role in stroke therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline development for acute ischemic stroke. Fagan, SC., Cronic, LE., Hess, DC.[2021]

Minocycline, administered intravenously within 6 hours of stroke onset, was found to be safe and well tolerated at doses up to 10 mg/kg, with only one instance of dose-limiting toxicity reported.

The drug has a half-life of approximately 24 hours, suggesting it can be effectively dosed every 24 hours, making it a potentially ideal treatment option to use alongside tissue plasminogen activator in acute ischemic stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Fagan, SC., Waller, JL., Nichols, FT., et al.[2023]

Minocycline, a commonly used antibiotic, has shown potential beyond its traditional use, demonstrating cytoprotective and neuroprotective effects that may benefit patients with cerebrovascular and neurodegenerative diseases.

Current literature suggests that minocycline's multi-faceted effects on cell functions make it a promising candidate for clinical trials targeting various conditions, including bacterial infections, cancer, and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline mediated mitochondrial cytoprotection: premises for therapy of cerebrovascular and neurodegenerative diseases. Karachitos, A., García Del Pozo, JS., de Groot, PW., et al.[2019]

Minocycline, traditionally an antibiotic, shows potential as a cardiovascular therapeutic due to its anti-inflammatory, antioxidant, and antiapoptotic properties, as supported by preclinical and clinical studies.

The review highlights ongoing clinical trials investigating minocycline's cardioprotective effects, emphasizing its promising role beyond its original use as an antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline: a bacteriostatic antibiotic with pleiotropic cardioprotective effects. Brenes-Salazar, JA.[2015]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Minocycline repurposing in critical illness: focus on stroke. [2021]

2. India pubmed.ncbi.nlm.nih.gov

Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Minocycline development for acute ischemic stroke. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. [2023]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Minocycline mediated mitochondrial cytoprotection: premises for therapy of cerebrovascular and neurodegenerative diseases. [2019]

7. Canada pubmed.ncbi.nlm.nih.gov

Minocycline: a bacteriostatic antibiotic with pleiotropic cardioprotective effects. [2015]