Focus of Study of Healthy AdultsPhase 1NCT01681836
Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
A Phase 1 study testing 15Nitrogen(15N)-labeled sodium nitrite and 15Nitrogen(15N)-labeled sodium nitrate in people with Focus of Study of Healthy Adults, run by Gladwin, Mark, MD at 1 site in United States.
Trial summary
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited toxicity in the doses proposed in healthy adult normal volunteers. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Focus of Study of Healthy Adults
- What is being tested?
- 15Nitrogen(15N)-labeled sodium nitrite and 15Nitrogen(15N)-labeled sodium nitrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Oct 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-60 years
- Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg
Who cannot join
- Positive urine pregnancy test or breastfeeding
- Concurrent use of medications affecting glucose or lipid metabolism
- Recent addition or change in dosing of hormonal contraceptive medications (oral contraceptive pill, intrauterine device, DepoProvera)
- Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or normotensive on a single agent
- Current use of phosphodiesterase 5 inhibitors or organic nitrates
- Not stable on treatments for the prior three months or not planning to remain on current dose of medications for blood pressure, contraception, etc
- Known chronic psychiatric or medical conditions including diabetes, liver or kidney disease or obesity syndromes
- Smoker
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited toxicity in the doses proposed in healthy adult normal volunteers. We utilize a powerful in vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and nitrite capsules for cardiovascular disease.
Read the detailed description
Preclinical and clinical research over the last decade has revealed the important vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure, vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway.
For this reason, development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway. This study aims to establish the pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric oxide in vivo in healthy adult normal volunteers.
- Conditions
- Focus of Study of Healthy Adults
- Being tested
- 15Nitrogen(15N)-labeled sodium nitrite, 15Nitrogen(15N)-labeled sodium nitrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
15Nitrogen(15N)-labeled sodium nitriteDrug
15Nitrogen(15N)-labeled sodium nitrite 20 mg once
15Nitrogen(15N)-labeled sodium nitrateDrug
15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
| Study group | Role | What they receive |
|---|---|---|
| Oral 15N-labeled sodium nitrate | Experimental | Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once Receives: Drug: 15Nitrogen(15N)-labeled sodium nitrite; Drug: 15Nitrogen(15N)-labeled sodium nitrate |
| Oral 15N-labeled sodium nitrite | Experimental | Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once Receives: Drug: 15Nitrogen(15N)-labeled sodium nitrite; Drug: 15Nitrogen(15N)-labeled sodium nitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Nitrate Concentration Over 24 Hour Study Period
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Peak Plasma Nitrite Concentration Over 24 Hour Study Period
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Secondary outcomes (7)
Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported
Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
Percent Platelet Activation at 6 Hours
at timepoint with greatest change from 0 (trough); "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry
Measured: measured at 0 (baseline), 6 and 24 hours post-dose
Peak Change in Heart Rate Over 24 Hour Study Period
"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Measured: measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Focus of Study of Healthy AdultsStudies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gladwin, Mark, MD
- Responsible party
- Principal investigator, Kara Hughan, University of Pittsburgh
- Investigators
- Kara S Hughan, MD, Principal investigator, University of PittsburghMark T Gladwin, MD, Study director, University of PittsburghBret Goodpaster, PhD, Study director, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01681836
- Sponsor's protocol ID
- PRO11120134
- Status last verified
- Aug 2018
- First submitted
- 3 Jul 2012
- Last updated
- 4 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hughan KS, Wendell SG, Delmastro-Greenwood M, Helbling N, Corey C, Bellavia L, Potti G, Grimes G, Goodpaster B, Kim-Shapiro DB, Shiva S, Freeman BA, Gladwin MT. Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate. Hypertension. 2017 Sep;70(3):634-644. doi: 10.1161/HYPERTENSIONAHA.117.09016.
PubMed 28739973
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
- ClinicalTrials.gov ID
- NCT01681836
- Acronym / sponsor ID
- PRO11120134
- Conditions
- Focus of Study of Healthy Adults
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Gladwin, Mark, MD
- Study start
- Oct 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 10 Sep 2012 (estimated)
- Results
- Posted 4 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited toxicity in the doses proposed in healthy adult normal volunteers. We utilize a powerful in vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and nitrite capsules for cardiovascular disease.
Detailed description
Preclinical and clinical research over the last decade has revealed the important vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure, vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway.
For this reason, development of an oral formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the nitrate would continuously provide a slow formation of nitrite over a prolonged period of time via the enterosalivary circulation pathway. This study aims to establish the pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric oxide in vivo in healthy adult normal volunteers.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral 15N-labeled sodium nitrate | Experimental | Drug: 15Nitrogen(15N)-labeled sodium nitrite, Drug: 15Nitrogen(15N)-labeled sodium nitrateOral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once |
| Oral 15N-labeled sodium nitrite | Experimental | Drug: 15Nitrogen(15N)-labeled sodium nitrite, Drug: 15Nitrogen(15N)-labeled sodium nitrateOral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age 18-60 years
- Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg
Key exclusion criteria (8 listed)
- Positive urine pregnancy test or breastfeeding
- Concurrent use of medications affecting glucose or lipid metabolism
- Recent addition or change in dosing of hormonal contraceptive medications (oral contraceptive pill, intrauterine device, DepoProvera)
- Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or normotensive on a single agent
- Current use of phosphodiesterase 5 inhibitors or organic nitrates
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 |
|---|---|---|
| 15Nitrogen(15N)-labeled sodium nitrite15Nitrogen(15N)-labeled sodium nitrite 20 mg once | Drug | Oral 15N-labeled sodium nitrate, Oral 15N-labeled sodium nitrite |
| 15Nitrogen(15N)-labeled sodium nitrate15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once | Drug | Oral 15N-labeled sodium nitrate, Oral 15N-labeled sodium nitrite |
Primary outcome
Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Peak Plasma Nitrite Concentration Over 24 Hour Study Period
Time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
Time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
7 secondary outcomes
Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
Time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
Time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported
Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
Time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
Time frame: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
Percent Platelet Activation at 6 Hours
Time frame: measured at 0 (baseline), 6 and 24 hours post-dose
Peak Change in Heart Rate Over 24 Hour Study Period
Time frame: measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28739973Hughan KS, Wendell SG, Delmastro-Greenwood M, Helbling N, Corey C, Bellavia L, Potti G, Grimes G, Goodpaster B, Kim-Shapiro DB, Shiva S, Freeman BA, Gladwin MT. Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate. Hypertension. 2017 Sep;70(3):634-644. doi: 10.1161/HYPERTENSIONAHA.117.09016.
Related trials for Focus of Study of Healthy Adults
RecruitingPhase 4
Reversible Effects of Oral Contraceptive Removal on Serotonergic Neurotransmission
The Focus of the Study is to Investigate Reversible Effects of Combined Oral Contraceptive Use on Serotonergic Neurotransmission, Healthy Adult Females
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.
Kara S Hughan, MD principal investigator
University of Pittsburgh
Mark T Gladwin, MD study director
University of Pittsburgh
Bret Goodpaster, PhD study director
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 15Nitrogen(15N)-labeled sodium nitrite and 15Nitrogen(15N)-labeled sodium nitrate in people with Focus of Study of Healthy Adults, run by Gladwin, Mark, MD 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 8 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 4 Sep 2018. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Peak Plasma Nitrate Concentration Over 24 Hour Study Period (time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses). The study lists 3 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 NCT01681836, which also lists 1 linked publication.
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 4 Sep 2018.