HypertensionEarly Phase 1NCT05798481
Effect of Sublingually Generated S-nitroso-N-acetylcysteine on Systemic Blood Pressure.
A Early Phase 1 study testing Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals. in people with Hypertension and Cardiovascular Diseases, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Cardiovascular Diseases
- What is being tested?
- Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2024to 5 Oct 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male and female subjects who are at least 21 years old and who consent to participate in the study.
- Participants must be willing to have approximately 15 mL of blood drawn via venipuncture and undergo blood pressure measurement.
Who cannot join
- Individuals who are below 21 years of age, pregnant, have major cardiovascular problems or sickle cell disease, incarcerated individuals or are unable to give consent will be excluded.
- Those whose blood pressure is below normal (i.e., 120/80) and those who have cardiovascular problems and taking organic nitrates and sildenafil-based drugs will also be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Anesthesiology and Perioperative Medicine
Birmingham, Alabama, 35294
About this study
Official title: A Pilot Pre-Phase 1 Clinical Trial to Study How Administering Sublingual Nitric Oxide Donor S-nitroso-N-acetylcysteine Affects the Systemic Blood Pressure in Healthy Human Volunteers.
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.
Read the detailed description
It is well established that increasing the bioavailability of endogenous nitric oxide (NO) protects against cardiovascular diseases. Administering exogenous NO donors is one option to increase endogenous NO levels. Organic nitrates like nitroglycerin have been used as NO donors to protect against angina and ischemic heart failure for over a century. However, their therapeutic value is compromised by rapid development of tolerance during sustained therapy. Hence, these drugs cannot be used as sustain sources of NO. Low-molecular-weight S-nitrosothiols are proven NO donors that have potent vasodilatory, antithrombotic, and anti-inflammatory activities. However, their prophylactic use is hindered by instability after preparation. Inorganic nitrite is emerging as a hypoxic vasodilator, but recent clinical studies indicate that high oral doses of >100 mg/day are required to improve vascular tone. To solve the problems of organic nitrates tolerance, S-nitrosothiol instability, and high nitrite dose requirements, the technique of generating S-nitrosoacetylcysteine (SNOAC) sublingually or in the stomach by reacting sodium nitrite with N-acetylcysteine (NAC) in rodent models was developed. This SNOAC is rapidly absorbed into circulation and increases plasma S-nitrosothiols and reduces systemic systolic and diastolic blood pressure. The major objective of the proposed pre-phase 1 study is to confirm the preclinical findings, including whether the procedure used to generate and deliver NO is feasible in humans using optimal levels of nitrite (2.5mg and 5mg) and NAC (50mg) and a minimum number of subjects. The study will assess the feasibility of using nitrite and NAC mixture sublingually, generation and absorption of SNOAC into circulation, and blood pressure response to the optimum doses of nitrite and NAC. This study will lay the groundwork for determining whether this NO delivery technique can be implemented to initiate comprehensive clinical studies. S-nitrosothiols, nitrite, and nitrate in plasma will be measured by highly sensitive chemiluminescence assay and monitor cardiovascular hemodynamics by FDA-approved mobil-O-graph for ambulatory subjects
- Conditions
- Hypertension, Cardiovascular Diseases
- Being tested
- Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.
- Keywords
- Nitric oxide, Sodium nitrite, N-acetylcysteine, S-nitrosothiols, systemic blood pressure, Vasodilators, Hypertension
- Medical subject headings
- Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.Drug
Exactly 2.5 mg or 5 mg sodium nitrite and 50 mg N-acetylcysteine are weighed and mixed together just before use. The mixture is placed under the participant's tongue. The powder slowly dissolves in saliva and generate S-nitrosoacetylcysteine. Investigators will ask the subjects not to swallow the drug at least for 30 min. Administration of nitrite and N-acetylcysteine individually at these concentrations is not expected to change any blood NO chemistry or the systemic blood pressure. Hence, investigators will not investigate the effects of nitrite and N-acetylcysteine individually in this study. Placebo control is not needed for this study because the baseline parameters will serve as control. Investigators will assess the drug effect based on the difference between pre-treatment and post-treatment values.
| Study group | Role | What they receive |
|---|---|---|
| sodium nitrite and N-acetycysteine mixture | Experimental | sodium nitrite 2.5mg + N-acetylcysteine 50mg
Sodium nitrite 5 mg + N-acetylcysteine 50mg Receives: Drug: Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of plasma nitrite, nitrate and S-nitrosothiols in the study participants.
Plasma level of nitrite, nitrate and S-nitrosothiols species (nanomol/L) will be measured by highly validated ozone-based chemiluminescience assay before, during and the end of sublingual administration of S-nitrosoacetylcysteine in study participants The drug effect will be assessed based on the change in the nitrite, nitrate and S-nitrosothiol values from the baseline levels following the administration of the drug.
Measured: up to 18 months
Measurement of Systemic systolic and diastolic blood pressure
The FDA approved Mobil-O-Graph blood pressure (BP) apparatus will be used to measure the BP parameters. BP is measured in units of millimeters of mercury (mmHg). The cuff will be wrapped around the left arm and the measurement time will be set for 120 minutes. Blood pressure parameters will be automatically measured at 2-minute intervals.
Measured: up to 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2023
- Study start27 Mar 2024
- Primary completion29 Apr 2025
- Study completion5 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The optimum levels of 2.5 mg and 5mg mg sodium nitrite and fixed amount of 50 mg N-acetylcysteine are used for this study. Total of 14 subjects are divided to two groups.Group 1 is tested with the low dose of 2.5 mg sodium nitrite. If no adverse effects are noticed in this group, the study is proceed for 2nd group with 5mg sodium nitrite.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nagababu Enika, University of Alabama at Birmingham
- Investigators
- Nagababu Enika, PhD, Principal investigator, University of Alabama at BirminghamBrant Wagener, MD, PhD, Study director, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05798481
- Sponsor's protocol ID
- IRB-300010325
- Status last verified
- Nov 2025
- First submitted
- 10 Mar 2023
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All the data will be shared through abstracts, presentation at conferences and publications.
Publications
Farah C, Michel LYM, Balligand JL. Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol. 2018 May;15(5):292-316. doi: 10.1038/nrcardio.2017.224. Epub 2018 Feb 1.
PubMed 29388567Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia. 1991 Mar;5(3):196-9.
PubMed 2013979Munzel T, Daiber A, Gori T. More answers to the still unresolved question of nitrate tolerance. Eur Heart J. 2013 Sep;34(34):2666-73. doi: 10.1093/eurheartj/eht249. Epub 2013 Jul 17.
PubMed 23864131Al-Sa'doni H, Ferro A. S-Nitrosothiols: a class of nitric oxide-donor drugs. Clin Sci (Lond). 2000 May;98(5):507-20.
PubMed 10781381Sun J, Murphy E. Protein S-nitrosylation and cardioprotection. Circ Res. 2010 Feb 5;106(2):285-96. doi: 10.1161/CIRCRESAHA.109.209452.
PubMed 20133913Daiber A, Xia N, Steven S, Oelze M, Hanf A, Kroller-Schon S, Munzel T, Li H. New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease. Int J Mol Sci. 2019 Jan 7;20(1):187. doi: 10.3390/ijms20010187.
PubMed 30621010
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Pre-Phase 1 Clinical Trial to Study How Administering Sublingual Nitric Oxide Donor S-nitroso-N-acetylcysteine Affects the Systemic Blood Pressure in Healthy Human Volunteers.
- ClinicalTrials.gov ID
- NCT05798481
- Acronym / sponsor ID
- IRB-300010325
- Conditions
- Hypertension, Cardiovascular Diseases
- Keywords
- Nitric oxide, Sodium nitrite, N-acetylcysteine, S-nitrosothiols, systemic blood pressure, Vasodilators, Hypertension
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 27 Mar 2024 (actual)
- Primary completion
- 29 Apr 2025 (actual)
- Study completion
- 5 Oct 2025 (actual)
- First posted
- 4 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
It is well established that increasing the bioavailability of endogenous nitric oxide (NO) protects against cardiovascular diseases. Administering exogenous NO donors is one option to increase endogenous NO levels. Organic nitrates like nitroglycerin have been used as NO donors to protect against angina and ischemic heart failure for over a century. However, their therapeutic value is compromised by rapid development of tolerance during sustained therapy. Hence, these drugs cannot be used as sustain sources of NO. Low-molecular-weight S-nitrosothiols are proven NO donors that have potent vasodilatory, antithrombotic, and anti-inflammatory activities. However, their prophylactic use is hindered by instability after preparation. Inorganic nitrite is emerging as a hypoxic vasodilator, but recent clinical studies indicate that high oral doses of >100 mg/day are required to improve vascular tone. To solve the problems of organic nitrates tolerance, S-nitrosothiol instability, and high nitrite dose requirements, the technique of generating S-nitrosoacetylcysteine (SNOAC) sublingually or in the stomach by reacting sodium nitrite with N-acetylcysteine (NAC) in rodent models was developed. This SNOAC is rapidly absorbed into circulation and increases plasma S-nitrosothiols and reduces systemic systolic and diastolic blood pressure. The major objective of the proposed pre-phase 1 study is to confirm the preclinical findings, including whether the procedure used to generate and deliver NO is feasible in humans using optimal levels of nitrite (2.5mg and 5mg) and NAC (50mg) and a minimum number of subjects. The study will assess the feasibility of using nitrite and NAC mixture sublingually, generation and absorption of SNOAC into circulation, and blood pressure response to the optimum doses of nitrite and NAC. This study will lay the groundwork for determining whether this NO delivery technique can be implemented to initiate comprehensive clinical studies. S-nitrosothiols, nitrite, and nitrate in plasma will be measured by highly sensitive chemiluminescence assay and monitor cardiovascular hemodynamics by FDA-approved mobil-O-graph for ambulatory subjects
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The optimum levels of 2.5 mg and 5mg mg sodium nitrite and fixed amount of 50 mg N-acetylcysteine are used for this study. Total of 14 subjects are divided to two groups.Group 1 is tested with the low dose of 2.5 mg sodium nitrite. If no adverse effects are noticed in this group, the study is proceed for 2nd group with 5mg sodium nitrite.
| Arm | Type | Receives |
|---|---|---|
| sodium nitrite and N-acetycysteine mixture | Experimental | Drug: Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.sodium nitrite 2.5mg + N-acetylcysteine 50mg Sodium nitrite 5 mg + N-acetylcysteine 50mg |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy male and female subjects who are at least 21 years old and who consent to participate in the study.
- Participants must be willing to have approximately 15 mL of blood drawn via venipuncture and undergo blood pressure measurement.
Key exclusion criteria (2 listed)
- Individuals who are below 21 years of age, pregnant, have major cardiovascular problems or sickle cell disease, incarcerated individuals or are unable to give consent will be excluded.
- Those whose blood pressure is below normal (i.e., 120/80) and those who have cardiovascular problems and taking organic nitrates and sildenafil-based drugs will also be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.Exactly 2.5 mg or 5 mg sodium nitrite and 50 mg N-acetylcysteine are weighed and mixed together just before use. The mixture is placed under the participant's tongue. The powder slowly dissolves in saliva and generate S-nitrosoacetylcysteine. Investigators will ask the subjects not to swallow the drug at least for 30 min. Administration of nitrite and N-acetylcysteine individually at these concentrations is not expected to change any blood NO chemistry or the systemic blood pressure. Hence, investigators will not investigate the effects of nitrite and N-acetylcysteine individually in this study. Placebo control is not needed for this study because the baseline parameters will serve as control. Investigators will assess the drug effect based on the difference between pre-treatment and post-treatment values. | Drug | sodium nitrite and N-acetycysteine mixture |
Primary outcome
Measurement of plasma nitrite, nitrate and S-nitrosothiols in the study participants.
Time frame: up to 18 months
Plasma level of nitrite, nitrate and S-nitrosothiols species (nanomol/L) will be measured by highly validated ozone-based chemiluminescience assay before, during and the end of sublingual administration of S-nitrosoacetylcysteine in study participants The drug effect will be assessed based on the change in the nitrite, nitrate and S-nitrosothiol values from the baseline levels following the administration of the drug.
Measurement of Systemic systolic and diastolic blood pressure
Time frame: up to 11 months
The FDA approved Mobil-O-Graph blood pressure (BP) apparatus will be used to measure the BP parameters. BP is measured in units of millimeters of mercury (mmHg). The cuff will be wrapped around the left arm and the measurement time will be set for 120 minutes. Blood pressure parameters will be automatically measured at 2-minute intervals.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Background: PubMed 29388567Farah C, Michel LYM, Balligand JL. Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol. 2018 May;15(5):292-316. doi: 10.1038/nrcardio.2017.224. Epub 2018 Feb 1.
- Background: PubMed 2013979Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia. 1991 Mar;5(3):196-9.
- Background: PubMed 23864131Munzel T, Daiber A, Gori T. More answers to the still unresolved question of nitrate tolerance. Eur Heart J. 2013 Sep;34(34):2666-73. doi: 10.1093/eurheartj/eht249. Epub 2013 Jul 17.
- Background: PubMed 10781381Al-Sa'doni H, Ferro A. S-Nitrosothiols: a class of nitric oxide-donor drugs. Clin Sci (Lond). 2000 May;98(5):507-20.
- Background: PubMed 20133913Sun J, Murphy E. Protein S-nitrosylation and cardioprotection. Circ Res. 2010 Feb 5;106(2):285-96. doi: 10.1161/CIRCRESAHA.109.209452.
- Background: PubMed 30621010Daiber A, Xia N, Steven S, Oelze M, Hanf A, Kroller-Schon S, Munzel T, Li H. New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease. Int J Mol Sci. 2019 Jan 7;20(1):187. doi: 10.3390/ijms20010187.
- Individual participant dataSharing planned: Yes. All the data will be shared through abstracts, presentation at conferences and publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nagababu Enika, PhD principal investigator
University of Alabama at Birmingham
Brant Wagener, MD, PhD study director
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals. in people with Hypertension and Cardiovascular Diseases, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of plasma nitrite, nitrate and S-nitrosothiols in the study participants. (time frame: up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05798481, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.