Nitrite + NAC Mix for High Blood Pressure

Overseen By Ayesha Ayesha, MD.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Organic nitrates, Sildenafil

Disqualifiers: Under 21, Pregnant, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 11 months

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking organic nitrates or sildenafil-based drugs, you will not be eligible to participate.

What data supports the effectiveness of the drug for high blood pressure?

Research shows that N-acetylcysteine (NAC) can enhance the blood pressure-lowering effects of certain medications and has been found to reduce blood pressure in some studies, particularly in younger individuals. Additionally, NAC has antioxidant properties that may help improve blood vessel function, which can contribute to lowering blood pressure. ^{1 2 3 4 5}

Is the combination of Nitrite and NAC safe for humans?

Research on N-acetylcysteine (NAC) shows it is generally safe and can enhance the effects of other treatments, like nitroglycerin, in heart conditions. It also has protective effects against high blood pressure in animal studies, suggesting it may be safe for human use, but specific safety data for the combination with nitrite is not available. ^{1 2 3 4 6}

What makes the Nitrite + NAC Mix drug unique for high blood pressure?

The Nitrite + NAC Mix is unique because it combines sodium nitrite and N-acetylcysteine (NAC) to potentially offer a novel mechanism for managing high blood pressure, unlike traditional treatments that often focus on different pathways. This combination may provide a new approach by leveraging the individual properties of nitrite and NAC, which have been studied for other uses but not commonly combined for this condition. ^{7 8 9 10 11}

What is the purpose of this trial?

The purpose of the study is to increase the in vivo levels of nitric oxide by generating nitric oxide donor compound S-nitrosoacetylcysteine (SNOAC) using the mixture of sodium nitrite and N-acetylcysteine crystals in the sublingual space. The generated SNOAC rapidly diffuses into blood circulation thereby decrease the systemic blood pressure. This compound can be an alternative to organic nitrate NO donor drugs without developing tolerance in patients.

Research Team

Nagababu Enika, PhD

Principal Investigator

University of Alabama at Birmingham

Brant Wagener, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for healthy men and women over 21 who agree to blood draws and blood pressure checks. It's not for those under 21, pregnant, with major heart issues or sickle cell disease, in jail, unable to consent, have low blood pressure or take certain heart medications.

Inclusion Criteria

I am at least 21 years old and agree to participate in the study.

I am willing to have my blood drawn and my blood pressure checked.

Exclusion Criteria

My blood pressure is normal or high, and I'm not on nitrates or sildenafil.

I am over 21, not pregnant, don't have major heart problems or sickle cell disease, not incarcerated, and can consent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sublingual administration of sodium nitrite and N-acetylcysteine to generate S-nitrosoacetylcysteine and measure its effects on systemic blood pressure

11 months

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crystals

Trial Overview The study tests a mix of Sodium Nitrite and N-acetylcysteine crystals placed under the tongue to create SNOAC. This may lower high blood pressure without the tolerance seen with some other nitrate drugs.

Participant Groups

Group I: sodium nitrite and N-acetycysteine mixture Experimental Treatment 1 Intervention

sodium nitrite 2.5mg + N-acetylcysteine 50mg Sodium nitrite 5 mg + N-acetylcysteine 50mg

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a study of 18 hypertensive smokers, the addition of N-acetylcysteine (NAC) to angiotensin-converting enzyme inhibitors (ACEIs) significantly enhanced the antihypertensive effect, leading to lower 24-hour and daytime blood pressure compared to ACEI alone.

The improved blood pressure control with NAC may be due to its ability to protect nitric oxide (NO) from oxidation, suggesting a potential NO-dependent mechanism for the enhanced efficacy of ACEIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients. Barrios, V., Calderón, A., Navarro-Cid, J., et al.[2019]

In a study involving 27 patients with evolving acute myocardial infarction, N-acetylcysteine (NAC) was found to be safe and resulted in significantly less oxidative stress compared to those not receiving NAC, as indicated by improved glutathione levels.

NAC treatment showed a trend towards faster reperfusion and better preservation of heart function, suggesting it may enhance the effectiveness of standard treatments like nitroglycerin and streptokinase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Arstall, MA., Yang, J., Stafford, I., et al.[2019]

N-acetylcysteine (NAC) treatment for 8 weeks significantly reduced blood pressure in young spontaneously hypertensive rats (SHRs), showing its potential as a preventive measure against hypertension.

In adult SHRs, NAC did not significantly lower blood pressure, suggesting that established hypertension may involve structural changes that limit the effectiveness of NAC, despite its ability to increase nitric oxide synthase activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension. Pechánová, O., Zicha, J., Kojsová, S., et al.[2013]

N-acetylcysteine (NAC) effectively relaxes rat aortic arteries that have been contracted, demonstrating a dose-dependent vasodilatory effect without relying on the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway.

The relaxation effect of NAC is partly due to its ability to activate voltage-gated potassium (K+) channels and decrease intracellular calcium levels in vascular smooth muscle cells, suggesting a novel mechanism for its protective effects against vascular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta. Han, WQ., Zhu, DL., Wu, LY., et al.[2013]

In a pilot study involving 35 patients with metabolic syndrome, N-acetylcysteine (NAC) significantly reduced insulin resistance, inflammation markers, and systolic blood pressure after 6 weeks of treatment, indicating its potential efficacy in managing metabolic syndrome.

NAC also improved lipid profiles by decreasing triglycerides and increasing HDL cholesterol, while enhancing nitric oxide levels and reducing oxidative stress, suggesting a multifaceted mechanism of action that could benefit patients with metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of N-Acetylcysteine on Metabolic Profile in Metabolic Syndrome Patients. Rani, M., Aggarwal, R., Vohra, K.[2021]

In a study with adult Wistar rats, the administration of N-acetylcysteine (NAC) alongside L-NAME treatment prevented increases in blood pressure and superoxide production, suggesting that reactive oxygen species play a significant role in the development of hypertension.

When NAC was given as a treatment after hypertension was established, it had only moderate effects on lowering blood pressure, indicating that its preventive use is more effective than therapeutic use in managing L-NAME-induced hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic N-acetylcysteine administration prevents development of hypertension in N(omega)-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species. Rauchová, H., Pechánová, O., Kunes, J., et al.[2015]

Calcium nitrite and calcium nitrate are effective in accelerating the hydration of concrete in cold weather, leading to improved early strength and reduced frost damage.

However, increasing the amount of nitrite-based accelerator also raises the risk of shrinkage and cracking in the concrete, indicating a trade-off between strength and durability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Mechanical and Shrinkage Behavior of Lowered Temperatures Cementitious Mortars Mixed with Nitrite-Nitrate Based Accelerator. Tomita, Y., Yoneyama, A., Choi, H., et al.[2020]

The study found that adding calcium nitrite to section-restoration mortar enhances the generation of hydration products, which improves the strength and durability of repaired reinforced concrete structures.

Using CO2 nanobubble water in combination with calcium nitrite further increases the formation of calcite-based CaCO3, leading to a denser cement matrix and better overall performance of the repair material.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study on Physical Properties of Mortar for Section Restoration Using Calcium Nitrite and CO2 Nano-Bubble Water. Kim, HJ., Choi, H., Choi, H., et al.[2020]

Different solvents, particularly hydrochloric acid and carbonic acid, significantly reduced the surface hardness of mineral trioxide aggregate (MTA) compared to calcium-enriched mixture (CEM) cement, indicating that MTA is more susceptible to these solvents.

The study evaluated the effects of various solvents on the hardness of MTA and CEM over 21 days, revealing that the type of cement influences its resistance to solvent exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Solvents for Retrieval of Mineral Trioxide Aggregate and Calcium-Enriched Mixture. Shojaee, NS., Adl, A., Sobhnamayan, F., et al.[2022]

Exposure to 2% NaOH-N-acetyl-L-cysteine (NAC) and benzalkonium chloride in trisodium phosphate (Zephiran-TSP) significantly reduced the viability of Nocardia isolates, indicating their potential as effective antimicrobial agents.

After 30 minutes of treatment, 2% NaOH-NAC reduced viable Nocardia cells by 10^2 to 10^6, while Zephiran-TSP reduced them by 10^4 or more, demonstrating strong efficacy in killing these bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of decontamination procedures on recovery of Nocardia spp. Murray, PR., Heeren, RL., Niles, AC.[2021]

The use of nitrite-nitrate based accelerators in concrete significantly enhances early strength due to the rapid formation of nitrite and nitrate hydrates, as well as ettringite, which helps prevent frost damage in cold weather.

However, while these accelerators improve early strength, their long-term effects can be detrimental, leading to a decrease in strength after Day 3 due to the formation of brittle needle-like hydrates and a reduction in beneficial C-S-H gel and Ca(OH)2 hydrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physicochemical Study on the Strength Development Characteristics of Cold Weather Concrete Using a Nitrite-Nitrate Based Accelerator. Choi, H., Inoue, M., Choi, H., et al.[2020]

References

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

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients. [2019]

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

N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta. [2013]

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

Effect of N-Acetylcysteine on Metabolic Profile in Metabolic Syndrome Patients. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Chronic N-acetylcysteine administration prevents development of hypertension in N(omega)-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Mechanical and Shrinkage Behavior of Lowered Temperatures Cementitious Mortars Mixed with Nitrite-Nitrate Based Accelerator. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Study on Physical Properties of Mortar for Section Restoration Using Calcium Nitrite and CO2 Nano-Bubble Water. [2020]

9. Iran pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Solvents for Retrieval of Mineral Trioxide Aggregate and Calcium-Enriched Mixture. [2022]

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

Effect of decontamination procedures on recovery of Nocardia spp. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Physicochemical Study on the Strength Development Characteristics of Cold Weather Concrete Using a Nitrite-Nitrate Based Accelerator. [2020]