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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment mix to lower high blood pressure. Researchers aim to determine if combining sodium nitrite and N-acetylcysteine (NAC) can safely increase nitric oxide levels in the body, potentially reducing blood pressure without the usual side effects. The trial seeks healthy adults without major heart issues or low blood pressure who are open to a blood draw and pressure check. As an Early Phase 1 trial, this research focuses on understanding how this new treatment works in people, offering participants the chance to be among the first to receive it.

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.

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

Research has shown that N-acetylcysteine (NAC), a component of the treatment, can lower blood pressure in both humans and animals, suggesting its potential safety. NAC also treats lung injuries from chemicals, further supporting its safety profile.

For sodium nitrite, less direct safety information exists for humans. However, the trial plans to combine it with NAC to create a new compound called S-nitrosoacetylcysteine (SNOAC). This compound aims to lower blood pressure without the tolerance issues seen with some other treatments.

As this is an early phase trial, the primary focus is on safety. This phase typically assesses how well participants tolerate the treatment. Therefore, researchers will closely monitor the trial for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the sodium nitrite and N-acetylcysteine (NAC) mixture for high blood pressure because it offers a novel approach compared to standard treatments like ACE inhibitors or beta-blockers. This combination works by releasing nitric oxide in the body, which helps relax and widen blood vessels, potentially lowering blood pressure more effectively and quickly. Additionally, the use of NAC may provide antioxidant benefits that could reduce oxidative stress, a factor often linked with hypertension. This unique mechanism of action sets it apart from conventional therapies and holds promise for improved blood pressure management.

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

Research has shown that a mix of sodium nitrite and N-acetylcysteine (NAC), which participants in this trial will receive, can help lower blood pressure. This combination forms a compound called S-nitrosoacetylcysteine (SNOAC) in the body, which quickly enters the bloodstream to reduce blood pressure. Previous studies found that SNOAC effectively lowers the average blood pressure in the arteries. In animal studies, NAC alone lowered blood pressure and reduced oxidative stress, which is damage caused by harmful molecules. These findings suggest that this treatment could be a promising alternative to current nitrate-based drugs for managing high blood pressure. ^{1 4 6 7 8}

Who Is on the Research Team?

Nagababu Enika, PhD

Principal Investigator

University of Alabama at Birmingham

Brant Wagener, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05798481

Effect of Sublingually Generated S-nitroso-N-acetylcysteine ... The generated SNOAC rapidly diffuses into blood circulation thereby decrease the systemic blood pressure. This compound can be an alternative to organic nitrate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4156139/

A nanoparticle delivery vehicle for S-nitroso-N-acetyl cysteine In vivo, intravenous infusion of the NAC-SNO-np and NO-np resulted in sustained decreases in mean arterial pressure, though NAC-SNO-np induced longer ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2721729/

The antihypertensive effect of cysteine - PMC In in vivo animal studies of hypertension, NAC not only reduced blood pressure but also was effective at reducing oxidative stress and improving antioxidant ...

4. ctv.veeva.com ctv.veeva.com/study/effect-of-sublingually-generated-s-nitroso-n-acetylcysteine-on-systemic-blood-pressure

Effect of Sublingually Generated S-nitroso-N-acetylcysteine on ... The generated SNOAC rapidly diffuses into blood circulation thereby decrease the systemic blood pressure. This compound can be an alternative to ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089860312002613

A nanoparticle delivery vehicle for S-nitroso-N-acetyl cysteine In vivo, intravenous infusion of the NAC-SNO-np and NO-np resulted in sustained decreases in mean arterial pressure, though NAC-SNO-np induced ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05798481?cond=Sodium%20Nitrite%20on&viewType=Table&rank=7

Effect of Sublingually Generated S-nitroso-N-acetylcysteine ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4087516/

Oral administration of S-nitroso-N-acetylcysteine prevents the ... Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats.

8. chemm.hhs.gov chemm.hhs.gov/countermeasure_acetylcysteine.htm

N-Acetylcysteine - Medical Countermeasures Database Treatment of chemical induced lung injury and respiratory toxicity including exposure to nerve agents, sulfur mustard gas, chlorine, phosgene.