MitoQ for High Blood Pressure

(MAVHS Trial)

Overseen By Zachary J Hutchison, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Auburn University

Must not be taking: Blood thinners

Disqualifiers: Cardiovascular disease, Cancer, Diabetes, Obesity, others

Compensation: Varies

Number of Visits: 2

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Black individuals are at increased cardiovascular disease risk. The central goal of the study is to determine if mitochondrial reactive oxygen species influence blood vessel function and nervous system regulation of blood pressure differentially in black, compared to white individuals. These findings may help to explain a potential mechanism that contributes to racial disparities in blood pressure and cardiovascular disease risk. A secondary goal is to determine if mitochondrial reactive oxygen species improves blood pressure and vascular function in individuals with elevated blood pressure and stage 1 hypertension.

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.

Is MitoQ safe for humans?

MitoQ has been studied in both animals and humans, showing no significant safety concerns in healthy adults, even at high doses. It has been used in various studies targeting mitochondrial oxidative stress without causing kidney injury or other major side effects. ^{1 2 3 4 5}

How does the drug MitoQ differ from other treatments for high blood pressure?

MitoQ is unique because it targets mitochondria, the energy-producing parts of cells, to reduce oxidative stress, which is a different approach compared to traditional blood pressure medications that often focus on relaxing blood vessels or reducing fluid volume. This novel mechanism may offer benefits for patients with resistant hypertension, where standard treatments are less effective. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for black and white individuals aged 19-75 with blood pressure no higher than 150/90 mmHg, a BMI below 35, not currently smoking or having smoked in the past year. They should be free from diabetes, kidney disease, pulmonary disorders, cardiovascular diseases, and must not be on blood thinners or have any issues that prevent exercise.

Inclusion Criteria

Have blood pressure no higher than 150/90 mmHg

My BMI is under 35.

I am between 19 and 75 years old.

Exclusion Criteria

I have a history of heart disease.

Communication barriers

I have a history of kidney disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including mental health, sleep quality, physical activity, cardiorespiratory fitness, and dietary intake

1 week

1 visit (in-person)

Treatment

Participants receive acute MitoQ supplementation or placebo, with assessments of sympathetic nerve activity, vascular function, blood pressure, and blood samples before and after supplementation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in flow-mediated dilation, blood biomarkers, muscle sympathetic nerve activity, arterial stiffness, blood pressure reactivity, and reactive oxygen species

1 hour post-supplementation

Treatment Details

Interventions

• MitoQ

Trial Overview The study tests if MitoQ affects blood vessel function and nervous system regulation of blood pressure differently across races. It aims to understand racial disparities in hypertension and cardiovascular risk by observing changes in those with elevated blood pressure or stage 1 hypertension.

Participant Groups

Group I: MitoQ Experimental Treatment 1 Intervention

Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after acute MitoQ supplementation (80 - 160mg).

Group II: Placebo Placebo Group 1 Intervention

Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a placebo matched in appearance to the MitoQ.

Who Is Running the Clinical Trial?

Auburn University

Lead Sponsor

Trials

81

Recruited

14,600+

Findings from Research

A sensitive and accurate liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay was developed to measure mitoquinone levels and its metabolites in rat plasma, demonstrating a linear calibration curve and a low limit of quantitation (0.5 ng/mL).

The pharmacokinetic study identified four metabolites of MitoQ10 in rat plasma, suggesting that MitoQ10 is effectively processed in the body, which is important for understanding its potential therapeutic effects in neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. Li, Y., Zhang, H., Fawcett, JP., et al.[2018]

Mitoquinone (MitoQ(10)) is effectively absorbed in the intestines, with 18-41% of the administered dose accumulating intracellularly, indicating its potential as a treatment for neurodegenerative diseases.

The absorption of MitoQ(10) can be significantly enhanced by the presence of serum proteins like bovine serum albumin, suggesting that its bioavailability may improve in real-life conditions despite some limitations from metabolism and transport proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. Li, Y., Fawcett, JP., Zhang, H., et al.[2018]

MitoQ(10), a mitochondria-targeted antioxidant, significantly reduced systolic blood pressure by approximately 25 mm Hg and improved endothelial function in stroke-prone spontaneously hypertensive rats over an 8-week treatment period.

MitoQ(10) also decreased cardiac hypertrophy compared to untreated controls and another compound, suggesting its potential as a novel therapeutic intervention for preventing hypertension and related cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Graham, D., Huynh, NN., Hamilton, CA., et al.[2021]

Acute high-dose MitoQ supplementation (100-160 mg) in 32 healthy adults showed no significant changes in urinary biomarkers associated with kidney injury, suggesting it is not nephrotoxic.

The study's results support the safety of MitoQ for further research on its effects related to mitochondrial oxidative stress, as it did not affect kidney function or injury markers in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute High Dose MitoQ Does not Increase Urinary Kidney Injury Markers in Healthy Adults. Linder, BA., Stute, NL., Hutchison, ZJ., et al.[2023]

In a study involving 50 male Wistar rats, the mitochondrial-targeted antioxidant MitoQ significantly improved survival rates (80%) and reduced tumor incidence (by 60% and 40% in different treatment groups) compared to those treated with diethyl nitrosamine (DEN) alone, indicating its potential as a protective agent against liver cancer.

MitoQ treatment also enhanced liver function and mitochondrial enzyme activities while reversing oxidative damage, suggesting that it effectively modulates mitochondrial antioxidant defenses and may serve as a promising chemotherapeutic agent in the context of DEN-induced hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems. Adisa, RA., Sulaimon, LA., Okeke, EG., et al.[2023]

Resistant hypertension, which is high blood pressure that doesn't respond to multiple medications, is becoming more common, and it can be confirmed by ruling out factors like poor medication adherence and secondary causes.

A thorough evaluation, including patient history and drug serum concentration checks, can significantly reduce the number of patients misdiagnosed with resistant hypertension, highlighting the importance of careful assessment in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Resistant hypertension : What is it?]. Luft, FC.[2018]

In a study of 50 patients with primary aldosteronism, good blood pressure control was achieved, with average 24-hour blood pressure readings of 130/77 mmHg, indicating effective management of hypertension.

80% of patients showed full adherence to their antihypertensive therapy, primarily using mineralocorticoid receptor antagonists like spironolactone and eplerenone, with eplerenone being favored due to side effects from spironolactone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence and blood pressure control in patients with primary aldosteronism. Nikrýnová Nguyen, TMP., Štrauch, B., Petrák, O., et al.[2022]

Recent studies highlight the potential of new antihypertensive drugs, such as aprocitentan, baxdrostat, and finerenone, which target specific pathways in resistant hypertension that current treatments do not address, showing promising safety and efficacy.

Catheter-based renal denervation has also been supported as a safe and effective additional treatment for resistant hypertension, providing new options for patients at high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation. Azzam, O., Nejad, SH., Carnagarin, R., et al.[2023]

The review highlights the lack of clear treatment algorithms for resistant arterial hypertension, emphasizing the need for tailored approaches based on individual patient characteristics such as hemodynamic type and plasma renin activity.

It discusses the potential effectiveness of using mineralocorticoid receptor antagonists as a primary strategy in managing resistant hypertension, suggesting that personalized treatment plans could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of resistant arterial hypertension. Shepeleva, NЕ., Rodionov, АV., Fomin, VV.[2019]

The AMBER study is investigating whether the potassium-binding polymer patiromer can safely allow the use of spironolactone in patients with resistant hypertension (RHTN) and chronic kidney disease (CKD), potentially preventing hyperkalemia, a common side effect.

This 12-week randomized trial includes 146 patients with an average age of 69.3 years and aims to determine if patiromer can help more patients remain on spironolactone, which is an effective treatment for hypertension, despite their reduced kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study. Agarwal, R., Rossignol, P., Garza, D., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. [2018]

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

Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. [2021]

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

Acute High Dose MitoQ Does not Increase Urinary Kidney Injury Markers in Healthy Adults. [2023]

5. Singapore pubmed.ncbi.nlm.nih.gov

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

[Resistant hypertension : What is it?]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Adherence and blood pressure control in patients with primary aldosteronism. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation. [2023]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of resistant arterial hypertension. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study. [2022]