Minocycline for High Blood Pressure

Overseen By Sarah Long, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Antibiotics, Anti-inflammatories, Glucocorticoids

Disqualifiers: Pregnancy, Intestinal surgery, 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: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether minocycline, a common antibiotic, can lower high blood pressure that resists other treatments. Researchers aim to determine if this effect relates to changes in brain areas controlling automatic functions like heart rate and blood pressure. Individuals with drug-resistant high blood pressure linked to nerve issues, who participated in a related study, might be suitable candidates. Participants must travel to Montreal for special brain imaging. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Do I need to stop taking my current medications for the trial?

Yes, you will need to stop taking certain medications, such as antibiotics, anti-inflammatory agents, and immune-modulating medications, before joining the trial.

Is there any evidence suggesting that minocycline is likely to be safe for humans?

Research has shown that minocycline has been used safely in other situations, though some side effects have been reported. While it treats conditions like acne, it has not been widely studied for high blood pressure. Common side effects include stomach issues and joint pain. More serious effects, such as increased pressure in the head affecting vision, have also been reported.

The safety of minocycline has not been confirmed for use beyond 12 weeks. This trial involves 26 weeks of treatment, so close monitoring of participants is important. Participants should discuss these risks with their doctor before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high blood pressure?

Researchers are excited about minocycline for high blood pressure because it offers a novel approach to treating neurogenic treatment-resistant hypertension. Unlike standard treatments like diuretics, ACE inhibitors, or beta-blockers, minocycline is an antibiotic that also has anti-inflammatory properties. This unique mechanism allows it to potentially address the inflammation associated with this specific type of high blood pressure. Additionally, minocycline's ability to cross the blood-brain barrier and its proposed neuroprotective effects make it a promising candidate for tackling hypertension that has a neurological component.

What evidence suggests that minocycline might be an effective treatment for high blood pressure?

Research has shown that minocycline, an antibiotic that also reduces inflammation, may help lower blood pressure in individuals whose high blood pressure does not respond to other treatments. In this trial, participants in the Minocycline Treatment Group will receive minocycline at the dose found most effective for lowering blood pressure. One study tested both low and high doses of minocycline and found it could reduce blood pressure and inflammation in these patients. Another study confirmed that minocycline lowered blood pressure over three months compared to a placebo. These findings suggest that minocycline might be effective for those with treatment-resistant hypertension. ^{6 7 8 9 10}

Who Is on the Research Team?

Carl Pepine, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for individuals with drug-resistant high blood pressure who are already part of another study (NCT02133885). Participants must be willing to travel to Montreal, Canada for brain imaging and testing. They should not be pregnant or have been so in the last 6 months, nor taking certain medications that could affect the study's outcome.

Inclusion Criteria

I am willing to travel to Montreal, Canada for special brain scans and tests.

Subjects participating in IRB approved protocol #102-2013 will be eligible to participate.

Exclusion Criteria

I have not taken antibiotics in the last 2 months.

Currently pregnant or have been pregnant in the last 6 months

Unwilling to discontinue vitamin or supplements, including probiotics, potentially affecting gut microbiota (vitamins/supplements and medications that possibly affect the gut microbiota should be discontinued for at least 2wks prior to stool collection)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Minocycline and undergo baseline and follow-up MRI and PET scans

12-24 weeks

Baseline and follow-up visits for MRI and PET scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Minocycline

Trial Overview The trial is studying whether Minocycline can lower blood pressure by reducing microglia activation in the brain. This will be measured using advanced imaging techniques like PET and MRI scans alongside Autonomic Nervous System Testing.

How Is the Trial Designed?

Group I: Minocycline Treatment Group Experimental Treatment 1 Intervention

Participants with neurogenic treatment-resistant hypertension who meet inclusion/exclusion criteria will receive minocycline at a dose determined to be most effective in lowering blood pressure (based on results from Study 1). Participants will undergo brain imaging with MRI and PET at baseline and 26 weeks. Intervention: Drug: Minocycline Dose: 50, 100, or 200 mg/day (based on optimal BP-lowering dose from Study 1) Frequency: Administered orally twice daily (BID) Duration: 26 weeks

Group II: Control Active Control 1 Intervention

Patients without a diagnosis of neurogenic (treatment-resistant) Hypertension and have not been treated with minocycline will be recruited. These participants will undergo one-time brain imaging visit (MRI and PET)

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 Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 56 oncology patients with vancomycin-resistant enterococci (VRE) infections, the combination of quinopristin-dalfopristin and minocycline showed a response rate of 68%, indicating its effectiveness against these infections.

The treatment was associated with a notable side effect, with 36% of patients experiencing arthralgia or myalgia, highlighting the need to consider potential adverse effects when using this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline. Raad, I., Hachem, R., Hanna, H., et al.[2018]

The review covers various topical antibacterial medications commonly used in veterinary dermatology, including their pharmacokinetics, mechanisms of action, and potential side effects, providing a comprehensive understanding of their clinical applications.

General recommendations for the use of topical antibacterial therapy in treating conditions like canine and feline pyoderma are presented, emphasizing the importance of selecting the appropriate medication based on specific clinical needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment of canine and feline pyoderma. Guaguere, E.[2021]

Dalbavancin shows promise as an effective treatment for resistant Gram-positive infections in children, with advantages such as fewer doses needed and lower potential for drug interactions, based on a review of 36 studies and ongoing clinical trials.

However, more research is necessary to determine the appropriate dosage and safety of dalbavancin in pediatric patients before it can be widely used in newborns and children, especially given the rise of multidrug-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalbavancin for the treatment of paediatric infectious diseases. Esposito, S., Bianchini, S.[2018]

Quinupristin/dalfopristin demonstrated strong in-vitro activity against Staphylococcus aureus, inhibiting all methicillin-sensitive strains at a concentration of 1 mg/L and 75% of methicillin-resistant strains at 1.5 mg/L.

This antibiotic could serve as a promising alternative treatment for methicillin-resistant staphylococcal infections, potentially reducing reliance on glycopeptide antibiotics like vancomycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative in vitro activity of quinupristin/dalfopristin and seven other antimicrobials against methicillin-susceptible and methicillin-resistant nosocomial Staphylococcus aureus bloodstream isolates. Nikolaidis, P., Metallidis, S., Katikaridou, E., et al.[2013]

Afabicin, a novel antibiotic targeting fatty acid synthesis in Staphylococcus spp., demonstrated comparable efficacy to vancomycin/linezolid in treating acute bacterial skin infections, with clinical response rates of 94.6% for low-dose afabicin and 90.1% for high-dose afabicin.

Both doses of afabicin were well tolerated, with mild side effects like headache and nausea, indicating its potential as a safe treatment option for staphylococcal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/Linezolid. Wittke, F., Vincent, C., Chen, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02133872

Study 1: Effect of Minocycline Treatment on Drug-Resistant ... This study is designed to evaluate a low and high dose of minocycline to test the hypothesis that minocycline treatment would produce antihypertensive effects ...

2. ahajournals.org ahajournals.org/doi/10.1161/hyp.68.suppl_1.p110

Abstract P110: Low Dose Minocycline Lowers BP and ... This study was to test the hypothesis that minocycline (Mino), an anti-inflammatory antibiotic, would lower BP and inflammatory markers in patient with TRH.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34348841/

Potential of Minocycline for Treatment of Resistant Hypertension Potential of Minocycline for Treatment of Resistant Hypertension.

4. withpower.com withpower.com/trial/phase-4-hypertension-resistant-to-conventional-therapy-3-2024-3c804

Minocycline for High Blood Pressure Trial Overview The study tests if minocycline can lower blood pressure in resistant cases over a 3-month period, compared to a placebo. It also explores ...

5. pharmacy.ufl.edu pharmacy.ufl.edu/2024/04/03/dr-steven-smith-leads-national-institutes-of-health-funded-study-to-determine-minocyclines-potential-to-address-treatment-resistant-hypertension/

Dr. Steven Smith leads National Institutes of Health-funded ... Dr. Steven Smith was awarded $3.3 million by the NIH to study the effects of the antibiotic minocycline on treatment-resistant hypertension.

6. mayoclinic.org mayoclinic.org/drugs-supplements/minocycline-oral-route/description/drg-20075715

Minocycline (oral route) - Side effects & dosage Safety and efficacy have not been established. Minocycline may cause ... increased blood pressure; increased thirst; indigestion; joint or ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/050808s014lbl.pdf

Solodyn (minocycline hydrochloride) tablet label Safety of SOLODYN® has not been established beyond 12 weeks of use. This ... Your doctor may do tests to check your blood for immune system reactions.

8. cdn.pfizer.com cdn.pfizer.com/pfizercom/products/material_safety_data/WP00046.pdf

Safety Data Sheet Repeated high exposure may affect the liver and nervous system. Target Organ(s) of Toxicity. No data available. LD50 Oral. Minocycline Hydrochloride. Ethanol.

9. drugs.com drugs.com/sfx/solodyn-side-effects.html

Solodyn Side Effects: Common, Severe, Long Term This medicine may cause an increased pressure in your head which can lead to permanent vision loss. Check with your doctor right away if you ...

10. webmd.com webmd.com/drugs/2/drug-7722-8073/minocycline-oral/minocycline-oral/details

Minocycline (Minocin, Minolira, and others) - Uses, Side ... Increased Pressure Around the Brain.​​ Minocycline can increase the pressure around the brain, a serious condition called pseudotumor cerebri or intracranial ...