Metabolic SyndromePhase 2ONPCNCT02517697
Oral Nitrite Trial for Hypertension and Metabolic Syndrome
A Phase 2 study testing 14 Nitrogen (N) Sodium Nitrite in people with Metabolic Syndrome and Hypertension, run by Gladwin, Mark, MD at 1 site in United States.
Trial summary
The objective of the study is to investigate effects of inorganic sodium nitrite on the cardiometabolic and hormonal disturbances observed in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Metabolic Syndrome, Hypertension
- What is being tested?
- 14 Nitrogen (N) Sodium Nitrite
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2020to 13 Apr 2021
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-60 years
- Body mass index (BMI) ≥ 30 kg/m2
- Hypertension: defined as systolic blood pressure ≥130 and/or diastolic blood pressure ≥85 mm Hg
- Waist circumference: >102 cm in men, >88 cm in women
Who cannot join
- Positive urine pregnancy test or breastfeeding
- Concurrent use of medications affecting glucose metabolism (oral hypoglycemics, insulin, atypical antipsychotics)
- Recent addition or change in dosing of hormonal contraceptive medications (Oral Contraceptive Pill (OCP), Intra Uterine Device (IUD), DepoProvera shot)
- Current use of ≥3 anti-hypertensive agents regardless of blood pressure control or normotensive on a single or double agent
- Current use of phosphodiesterase-5 (PD) inhibitors or organic nitrates. We will not exclude for dietary sources of nitrate/nitrite.
- Not stable on treatments for the prior three months or not planning to remain on current dose of medications for blood pressure, contraception, etc.
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- Known chronic psychiatric or medical conditions including diabetes, liver or kidney disease or obesity syndromes
- Thyroid Stimulating Hormone (TSH) >8 milli-International unit/mL
- Smoker
- Anemia (central lab hemoglobin < 11g/dL)
- Active periodontal disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Nitrite Modulation of Hypertension, Platelet Activation, and Endothelial and Mitochondrial Function
The objective of the study is to investigate effects of inorganic sodium nitrite on the cardiometabolic and hormonal disturbances observed in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction.
Read the detailed description
Cardiovascular disease remains the leading cause of death in the United States and worldwide. Several studies have demonstrated that fruit and vegetable rich diets significantly reduced blood pressure and reduced the risk of ischemic stroke and cardiovascular disease in general, the exact mechanisms remain poorly understood. 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. More recent findings suggest that inorganic nitrate and nitrite therapy may be involved in the regulation of glucose-insulin homeostasis.
For this reason, development of an oral formulation of nitrite salt represents a rational avenue of exploration for the treatment of cardiovascular diseases, whereby nitrite would ensure rapid acting effects upon absorption. Nitrite could then be oxidized to nitrate via the enterosalivary circulation pathway. In this pathway, about 25% of circulating nitrate is concentrated in the saliva and reduced to nitrite by commensal mouth bacteria with nitrate reductase enzymes. The proposal will investigate the inorganic nitrite effects (in any form) on insulin sensitivity in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction. This will be the third human trial using orally delivered nitrite (previously as aqueous solution).
- Conditions
- Metabolic Syndrome, Hypertension
- Being tested
- 14 Nitrogen (N) Sodium Nitrite, Placebo
- Medical subject headings
- Metabolic Syndrome, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
14 Nitrogen (N) Sodium NitriteDrug
Also called sodium nitrite
oral formulation of sodium nitrite 40 mg three times daily for 12 weeks
PlaceboDrug
oral formulation of matching placebo three times daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Active drug | Experimental | 14 Nitrogen (N) Sodium Nitrite 40mg three times daily (TID) Receives: Drug: 14 Nitrogen (N) Sodium Nitrite |
| Placebo | Placebo comparator | placebo capsules three time daily (TID) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin sensitivity (i.e. insulin stimulated glucose disposal)
obtained by hyperinsulinemic euglycemic clamp
Measured: baseline and 12 weeks
Secondary outcomes (4)
Change in systolic blood pressure
ambulatory blood pressure
Measured: baseline and 12 weeks
Change in mean arterial pressure
ambulatory blood pressure
Measured: baseline and then biweekly throughout the 12 week treatment
Change in diastolic blood pressure
ambulatory blood pressure
Measured: baseline and 12 weeks
Change in methemoglobin level
by co-oximetry
Measured: baseline and then biweekly throughout the 12 week treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2015 (estimated)
- Study startOct 2020 (estimated)
- Primary completion13 Apr 2021
- Study completion13 Apr 2021
Why it stopped: We will not initiate recruitment for this protocol due to lack of funding to support this placebo-controlled trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gladwin, Mark, MD
- Responsible party
- Principal investigator, Kara S Hughan, MD, University of Pittsburgh
- Investigators
- Kara S Hughan, MD, Principal investigator, University of PittsburghMark Gladwin, MD, Study director, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02517697
- Sponsor's protocol ID
- PRO15050540
- Acronym
- ONPC
- Status last verified
- Apr 2021
- First submitted
- 5 Aug 2015
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrite Modulation of Hypertension, Platelet Activation, and Endothelial and Mitochondrial Function
- ClinicalTrials.gov ID
- NCT02517697
- Acronym / sponsor ID
- ONPC / PRO15050540
- Conditions
- Metabolic Syndrome, Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: We will not initiate recruitment for this protocol due to lack of funding to support this placebo-controlled trial.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Gladwin, Mark, MD
- Study start
- Oct 2020 (estimated)
- Primary completion
- 13 Apr 2021 (actual)
- Study completion
- 13 Apr 2021 (actual)
- First posted
- 7 Aug 2015 (estimated)
- 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 objective of the study is to investigate effects of inorganic sodium nitrite on the cardiometabolic and hormonal disturbances observed in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction.
Detailed description
Cardiovascular disease remains the leading cause of death in the United States and worldwide. Several studies have demonstrated that fruit and vegetable rich diets significantly reduced blood pressure and reduced the risk of ischemic stroke and cardiovascular disease in general, the exact mechanisms remain poorly understood. 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. More recent findings suggest that inorganic nitrate and nitrite therapy may be involved in the regulation of glucose-insulin homeostasis.
For this reason, development of an oral formulation of nitrite salt represents a rational avenue of exploration for the treatment of cardiovascular diseases, whereby nitrite would ensure rapid acting effects upon absorption. Nitrite could then be oxidized to nitrate via the enterosalivary circulation pathway. In this pathway, about 25% of circulating nitrate is concentrated in the saliva and reduced to nitrite by commensal mouth bacteria with nitrate reductase enzymes. The proposal will investigate the inorganic nitrite effects (in any form) on insulin sensitivity in a targeted population of overweight/obese adults with metabolic syndrome and hypertension, at risk for insulin resistance and endothelial dysfunction. This will be the third human trial using orally delivered nitrite (previously as aqueous solution).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active drug | Experimental | Drug: 14 Nitrogen (N) Sodium Nitrite14 Nitrogen (N) Sodium Nitrite 40mg three times daily (TID) |
| Placebo | Placebo comparator | Drug: Placeboplacebo capsules three time daily (TID) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 18-60 years
- Body mass index (BMI) ≥ 30 kg/m2
- Hypertension: defined as systolic blood pressure ≥130 and/or diastolic blood pressure ≥85 mm Hg
- Waist circumference: >102 cm in men, >88 cm in women
Key exclusion criteria (11 listed)
- Positive urine pregnancy test or breastfeeding
- Concurrent use of medications affecting glucose metabolism (oral hypoglycemics, insulin, atypical antipsychotics)
- Recent addition or change in dosing of hormonal contraceptive medications (Oral Contraceptive Pill (OCP), Intra Uterine Device (IUD), DepoProvera shot)
- Current use of ≥3 anti-hypertensive agents regardless of blood pressure control or normotensive on a single or double agent
- Current use of phosphodiesterase-5 (PD) inhibitors or organic nitrates. We will not exclude for dietary sources of nitrate/nitrite.
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 |
|---|---|---|
| 14 Nitrogen (N) Sodium NitriteAlso: sodium nitriteoral formulation of sodium nitrite 40 mg three times daily for 12 weeks | Drug | Active drug |
| Placebooral formulation of matching placebo three times daily for 12 weeks | Drug | Placebo |
Primary outcome
Change in insulin sensitivity (i.e. insulin stimulated glucose disposal)
Time frame: baseline and 12 weeks
obtained by hyperinsulinemic euglycemic clamp
4 secondary outcomes
Change in systolic blood pressure
Time frame: baseline and 12 weeks
Change in mean arterial pressure
Time frame: baseline and then biweekly throughout the 12 week treatment
Change in diastolic blood pressure
Time frame: baseline and 12 weeks
Change in methemoglobin level
Time frame: baseline and then biweekly throughout the 12 week treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Individual participant dataSharing planned: No
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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.
Kara S Hughan, MD principal investigator
University of Pittsburgh
Mark Gladwin, MD 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 2 study testing 14 Nitrogen (N) Sodium Nitrite in people with Metabolic Syndrome and Hypertension, 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 4 inclusion and 11 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: withdrawn, as of the sponsor's last update on 19 Apr 2021. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Change in insulin sensitivity (i.e. insulin stimulated glucose disposal) (time frame: baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Apr 2021; AzTrials last refreshed its copy on 7 Nov 2026.