- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05798481
Effect of Sublingually Generated S-nitroso-N-acetylcysteine on Systemic Blood Pressure.
March 27, 2024 updated by: Nagababu Enika, University of Alabama at Birmingham
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
14
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Raneisha Lee, M.S.
- Phone Number: (205) 432-8656
- Email: raneisha@uab.edu
Study Contact Backup
- Name: Ayesha Ayesha, MD.
- Phone Number: (205) 996-9669
- Email: asbryant@uabmc.edu
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- Recruiting
- Anesthesiology and Perioperative Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: sodium nitrite and N-acetycysteine mixture
sodium nitrite 2.5mg + N-acetylcysteine 50mg Sodium nitrite 5 mg + N-acetylcysteine 50mg |
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
up to 18 months
|
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.
|
up to 11 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Nagababu Enika, PhD, University of Alabama at Birmingham
- Study Director: Brant Wagener, MD, PhD, University of Alabama at Birmingham
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
- 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.
- Al-Sa'doni H, Ferro A. S-Nitrosothiols: a class of nitric oxide-donor drugs. Clin Sci (Lond). 2000 May;98(5):507-20.
- Sun J, Murphy E. Protein S-nitrosylation and cardioprotection. Circ Res. 2010 Feb 5;106(2):285-96. doi: 10.1161/CIRCRESAHA.109.209452.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2024
Primary Completion (Estimated)
September 30, 2025
Study Completion (Estimated)
December 31, 2025
Study Registration Dates
First Submitted
March 10, 2023
First Submitted That Met QC Criteria
March 23, 2023
First Posted (Actual)
April 4, 2023
Study Record Updates
Last Update Posted (Actual)
March 28, 2024
Last Update Submitted That Met QC Criteria
March 27, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Vascular Diseases
- Hypertension
- Cardiovascular Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- IRB-300010325
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
All the data will be shared through abstracts, presentation at conferences and publications.
IPD Sharing Time Frame
August 2024
IPD Sharing Access Criteria
www.clinicaltrials.gov
and UAB websites
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cardiovascular Diseases
-
Medical College of WisconsinActive, not recruitingCardiovascular Diseases | Cardiovascular Risk Factor | Cardiovascular HealthUnited States
-
Hospital Mutua de TerrassaCompleted
-
Oregon Health and Science UniversityCompletedCardiovascular Disease | Cardiovascular Risk FactorsUnited States
-
Women's College HospitalUniversity Health Network, Toronto; Sunnybrook Health Sciences Centre; Brigham... and other collaboratorsUnknownCARDIOVASCULAR DISEASESCanada, United States
-
Groupe Hospitalier Paris Saint JosephTerminatedCARDIOVASCULAR DISEASESFrance
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
-
VA Office of Research and DevelopmentNot yet recruitingCardiovascular DiseaseUnited States
-
Baptist Health South FloridaUniversity of California, Los Angeles; Quest Diagnostics-Nichols InsituteActive, not recruitingCardiovascular DiseaseUnited States
-
Laval UniversityActive, not recruitingCardiovascular DiseaseCanada
-
Penn State UniversityCalifornia Healthcare InstituteCompleted
Clinical Trials on Mixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.
-
VA Office of Research and DevelopmentNational Center for Complementary and Integrative Health (NCCIH)CompletedDiabetic Nephropathy | Proteinuria | Oxidative StressUnited States
-
Medical University of South CarolinaNational Institute on Drug Abuse (NIDA)Completed
-
Kevin Gray, MDCompleted
-
Federal University of Rio Grande do SulHospital de Clinicas de Porto Alegre; Programa de pós-graduação em endocrinologiaCompletedIschemic Heart Disease | Acute Myocardial Infarction | Euthyroid Sick SyndromeBrazil
-
Otologic Pharmaceutics, Inc.CompletedHearing Loss | Sensorineural Hearing Loss | Noise-Induced Hearing LossUnited States
-
Indiana UniversityBioAdvantex PharmaCompletedHIV | Endothelial Dysfunction | Oxidative StressUnited States
-
Baylor Research InstituteCompleted
-
University of MichiganTerminatedInterstitial Lung Disease | Connective Tissue DiseaseUnited States
-
University of ChicagoNational Institute on Drug Abuse (NIDA); University of MinnesotaCompletedTobacco Use Disorder | GamblingUnited States
-
Beth Israel Deaconess Medical CenterCumberland PharmaceuticalsCompletedRadiocontrast NephropathyUnited States