Effect of Sublingually Generated S-nitroso-N-acetylcysteine on Systemic Blood Pressure.

NCT05798481 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB-300010325
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hypertension; Cardiovascular Diseases

Keywords

Nitric oxide; Sodium nitrite; N-acetylcysteine; S-nitrosothiols; systemic blood pressure; Vasodilators; Hypertension

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 11 months

Study Arms (1)

sodium nitrite and N-acetycysteine mixture

EXPERIMENTAL

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

Drug: Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.

Interventions

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.

sodium nitrite and N-acetycysteine mixture

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

Anesthesiology and Perioperative Medicine

Birmingham, Alabama, 35294, United States

Location

Related Publications (6)

• 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.

  PMID: 29388567 BACKGROUND

• Secker-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.

  PMID: 2013979 BACKGROUND

• Munzel 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.

  PMID: 23864131 BACKGROUND

• Al-Sa'doni H, Ferro A. S-Nitrosothiols: a class of nitric oxide-donor drugs. Clin Sci (Lond). 2000 May;98(5):507-20.

  PMID: 10781381 BACKGROUND

• Sun J, Murphy E. Protein S-nitrosylation and cardioprotection. Circ Res. 2010 Feb 5;106(2):285-96. doi: 10.1161/CIRCRESAHA.109.209452.

  PMID: 20133913 BACKGROUND

• Daiber 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.

  PMID: 30621010 BACKGROUND

MeSH Terms

Conditions

Hypertension; Cardiovascular Diseases

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Nagababu Enika, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Brant Wagener, MD, PhD

  University of Alabama at Birmingham

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: March 10, 2023
• First Posted: April 4, 2023
• Study Start: March 27, 2024
• Primary Completion: April 29, 2025
• Study Completion: October 5, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: August 2024
• Access Criteria: www.clinicaltrials.gov and UAB websites

Locations

US (1)