HypertensionPhase 1HYCANCT02527837
The Effect of Sodium Nitrite on Renal Function and Blood Pressure in Hypertensive Versus Healthy Subjects
A Phase 1 study testing Sodium nitrite and Sodium chloride in people with Hypertension, run by Erling Bjerregaard Pedersen at 1 site in Denmark.
Trial summary
The purpose of this study is to investigate how the effect of infused sodium nitrite differs in hypertensives compared to healthy age and sex matched controls. The effects on renal handling of nitrite, nitrate, sodium and water, plasma concentrations of vasoactive hormones, peripheral (brachial) and central blood… Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- Sodium nitrite and Sodium chloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- May 2015to Oct 2016
- Phase
- 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 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI 18.5-30.0
- Ambulatory daytime blood pressure >135 mmHg systolic and/or >85 mmHg diastolic
- Women of childbearing potential must use safe contraception
- BMI 18.5-30.0
- Women of childbearing potential must use safe contraception
Who cannot join
- Tobacco smoking, medicine or substance abuse
- Weekly consumption of more than 14 units (12 g alcohol per unit) for women and 21 units for men
- Pregnancy or nursing
- Neoplasia
- Clinically significant heart, lung, liver, kidney, metabolic or neurologic disease
- Albuminuria > 300 mg/L
Show all 27Show fewer
- Renography with signs of renal artery stenosis or hydronephrosis
- Clinically signs of secondary hypertension
- Clinically significant hypokalemia
- Clinically significant anemia
- Estimated glomerular filtration rate (eGFR) < 60 ml/min
- Clinically significant findings in screening blood samples, urine sample or ECG
- Persistent office blood pressure > 170/105 mmHg on the maximum dose of amlodipine (10 mg daily)
- Unacceptable symptoms of elevated blood pressure
- Unacceptable side effects of amlodipine
- Tobacco smoking, medicine or substance abuse
- Weekly consumption of more than 14 units (12 g alcohol per unit) for women and 21 units for men
- Medical treatment 2 weeks prior to each examination day, except for contraception
- Pregnancy or nursing
- Neoplasia
- Clinically significant heart, lung, liver, kidney, metabolic or neurologic disease
- Clinically significant albuminuria
- Clinically significant anemia
- Estimated glomerular filtration rate (eGFR) < 60 ml/min
- Clinically significant findings in screening blood samples, urine sample or ECG
- Ambulatory daytime blood pressure >135/85 mmHg
- Blood donation within 1 month of the first examination day
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Medical Research and Medicine, Holstebro Regional Hospital
Holstebro, Holstebro, 7500
Jeppe B Rosenbaek, MD, +4578436585, jepros@rm.dk
Jeppe B Rosenbaek, MD
About this study
Official title: The Effect of Sodium Nitrite Infusion on Renal Variables, Peripheral and Central Blood Pressure in Hypertensive Versus Normotensive Subjects in a Randomised, Placebo Controlled, Cross Over, Case-control Study
The purpose of this study is to investigate how the effect of infused sodium nitrite differs in hypertensives compared to healthy age and sex matched controls. The effects on renal handling of nitrite, nitrate, sodium and water, plasma concentrations of vasoactive hormones, peripheral (brachial) and central blood pressure will be evaluated.
Read the detailed description
Nitric oxide (NO) is an important vasodilating molecule with a very complex biochemistry and metabolism. NO is classically synthesized from L-arginin by endothelial nitric oxide synthase (eNOS) located in the endothelial cell lining. Several chronic cardiovascular diseases such as hypertension, chronic kidney disease and diabetes are accompanied by endothelial dysfunction and hence diminished synthesis of NO. NO is a very reactive molecule and direct investigation of its function are limited and it has mainly been investigated by inhibition of eNOS. Recent research has shown that sodium nitrite is readily converted to NO by enzymes in vivo. The effects of sodium nitrite on renal variables, vasoactive hormones and central blood pressure are previously unexamined. It is now possible to achieve serial estimations of the central aortic systolic pressure (CASP) by a wrist born device.
Hypothesis:
- Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR)
- Sodium nitrite infusion increases plasma levels of nitrite, nitrate, NO and cyclic guanosine monophosphate (cGMP)
- Sodium nitrite infusion lowers the peripheral and central blood pressure
- Renal clearance of nitrite is constant and not dose dependent
- Sodium nitrite infusion affects vasoactive hormones
- The hemodynamic and renal effects is more pronounced in hypertensives as compared to healthy controls.
Purpose:
The purpose of this study is to investigate the effects of sodium nitrite infusion on
- Renal handling of nitrite, nitrate, sodium and water
- Plasma concentrations of vasoactive hormones
- Peripheral (brachial) blood pressure and CASP
Design:
15 hypertensive subjects and 15 healthy, age and sex matched controls is recruited. Each subject will attend to two examination days. Four days prior to each examination day subjects are given a standardized diet with a low level of nitrate and nitrite. On the evening before the examination day the subjects take a single dose of lithium carbonate 300 mg in order to measure lithium clearance. On the examination days subjects are receiving a two hour infusion of either placebo (isotonic sodium chloride) or sodium nitrite. During the two examination days each subject receives both treatments in random order.
Perspectives:
Increasing knowledge about the nitrite-NO system can contribute to changing the clinical practise of diagnostics and treatment of cardiovascular diseases.
- Conditions
- Hypertension
- Being tested
- Sodium nitrite, Sodium chloride
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium nitriteDrug
Also called NaNO2
Sodium nitrite, 240 micrograms/kg/hour for 2 hours
Sodium chlorideDrug
Also called NaCl
Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours
| Study group | Role | What they receive |
|---|---|---|
| Sodium nitrite | Active comparator | Sodium nitrite, 240 micrograms/kg/hour for 2 hours Receives: Drug: Sodium nitrite |
| Placebo | Placebo comparator | Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours Receives: Drug: Sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional urinary sodium excretion (FENa)
Measured: 1 day
Secondary outcomes (18)
Peripheral (brachial) blood pressure
Measured by oscillometric sphygmomanometer
Measured: 1 day
Central aortic systolic blood pressure (CASP)
Measured by tonometric pulse wave analysis. Device BPro from HealthSTATS international, Singapore
Measured: 1 day
Plasma concentration of nitrite and nitrate (NOx)
Measured: 1 day
Urinary excretion of nitrite and nitrate (NOx)
Measured: 1 day
Glomerular filtration rate
Measured: 1 day
Proximal sodium transport (Estimated by lithium clearance)
Estimated by lithium clearance
Measured: 1 day
Free water clearance
Measured: 1 day
Urinary excretion of cyclic guanosine monophosphate (cGMP)
Measured: 1 day
Urinary excretion of epithelial sodium channels (ENaC)
Measured: 1 day
Urinary excretion of aquaporin 2 water channels (AQP2)
Measured: 1 day
Plasma concentration of renin (PRC)
Measured: 1 day
Plasma concentration of angiotensin II (ANG2)
Measured: 1 day
Plasma concentration of aldosterone
Measured: 1 day
Plasma concentration of atrial natriuretic peptide (ANP)
Measured: 1 day
Plasma concentration of brain natriuretic peptide (BNP)
Measured: 1 day
Plasma concentration of cyclic guanosine monophosphate (cGMP)
Measured: 1 day
Plasma concentration of endothelin
Measured: 1 day
Plasma concentration of vasopressin (AVP, ADH)
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2016 (estimated)
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erling Bjerregaard Pedersen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Erling Bjerregaard Pedersen, Regional Hospital Holstebro
- Investigators
- Erling B Pedersen, MD, DMSc, Principal investigator, Holstebro Regional Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527837
- Sponsor's protocol ID
- JBR-1-2014
- Acronym
- HYCA
- Status last verified
- Feb 2015
- First submitted
- 18 Feb 2015
- Last updated
- 19 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Rosenbaek JB, Hornstrup BG, Jorgensen AN, Mortensen J, Pedersen EB, Bech JN. Effects of sodium nitrite on renal function and blood pressure in hypertensive vs. healthy study participants: a randomized, placebo-controlled, crossover study. J Hypertens. 2018 Mar;36(3):666-679. doi: 10.1097/HJH.0000000000001598.
PubMed 29065098
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sodium Nitrite Infusion on Renal Variables, Peripheral and Central Blood Pressure in Hypertensive Versus Normotensive Subjects in a Randomised, Placebo Controlled, Cross Over, Case-control Study
- ClinicalTrials.gov ID
- NCT02527837
- Acronym / sponsor ID
- HYCA / JBR-1-2014
- Conditions
- Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Erling Bjerregaard PedersenUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 19 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 purpose of this study is to investigate how the effect of infused sodium nitrite differs in hypertensives compared to healthy age and sex matched controls. The effects on renal handling of nitrite, nitrate, sodium and water, plasma concentrations of vasoactive hormones, peripheral (brachial) and central blood pressure will be evaluated.
Detailed description
Nitric oxide (NO) is an important vasodilating molecule with a very complex biochemistry and metabolism. NO is classically synthesized from L-arginin by endothelial nitric oxide synthase (eNOS) located in the endothelial cell lining. Several chronic cardiovascular diseases such as hypertension, chronic kidney disease and diabetes are accompanied by endothelial dysfunction and hence diminished synthesis of NO. NO is a very reactive molecule and direct investigation of its function are limited and it has mainly been investigated by inhibition of eNOS. Recent research has shown that sodium nitrite is readily converted to NO by enzymes in vivo. The effects of sodium nitrite on renal variables, vasoactive hormones and central blood pressure are previously unexamined. It is now possible to achieve serial estimations of the central aortic systolic pressure (CASP) by a wrist born device.
Hypothesis:
- Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR)
- Sodium nitrite infusion increases plasma levels of nitrite, nitrate, NO and cyclic guanosine monophosphate (cGMP)
- Sodium nitrite infusion lowers the peripheral and central blood pressure
- Renal clearance of nitrite is constant and not dose dependent
- Sodium nitrite infusion affects vasoactive hormones
- The hemodynamic and renal effects is more pronounced in hypertensives as compared to healthy controls.
Purpose:
The purpose of this study is to investigate the effects of sodium nitrite infusion on
- Renal handling of nitrite, nitrate, sodium and water
- Plasma concentrations of vasoactive hormones
- Peripheral (brachial) blood pressure and CASP
Design:
15 hypertensive subjects and 15 healthy, age and sex matched controls is recruited. Each subject will attend to two examination days. Four days prior to each examination day subjects are given a standardized diet with a low level of nitrate and nitrite. On the evening before the examination day the subjects take a single dose of lithium carbonate 300 mg in order to measure lithium clearance. On the examination days subjects are receiving a two hour infusion of either placebo (isotonic sodium chloride) or sodium nitrite. During the two examination days each subject receives both treatments in random order.
Perspectives:
Increasing knowledge about the nitrite-NO system can contribute to changing the clinical practise of diagnostics and treatment of cardiovascular diseases.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sodium nitrite | Active comparator | Drug: Sodium nitriteSodium nitrite, 240 micrograms/kg/hour for 2 hours |
| Placebo | Placebo comparator | Drug: Sodium chlorideSodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- BMI 18.5-30.0
- Ambulatory daytime blood pressure >135 mmHg systolic and/or >85 mmHg diastolic
- Women of childbearing potential must use safe contraception
- BMI 18.5-30.0
- Women of childbearing potential must use safe contraception
Key exclusion criteria (27 listed)
- Tobacco smoking, medicine or substance abuse
- Weekly consumption of more than 14 units (12 g alcohol per unit) for women and 21 units for men
- Pregnancy or nursing
- Neoplasia
- Clinically significant heart, lung, liver, kidney, metabolic or neurologic disease
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 |
|---|---|---|
| Sodium nitriteAlso: NaNO2Sodium nitrite, 240 micrograms/kg/hour for 2 hours | Drug | Sodium nitrite |
| Sodium chlorideAlso: NaClSodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours | Drug | Placebo |
Primary outcome
Fractional urinary sodium excretion (FENa)
Time frame: 1 day
18 secondary outcomes
Peripheral (brachial) blood pressure
Time frame: 1 day
Central aortic systolic blood pressure (CASP)
Time frame: 1 day
Plasma concentration of nitrite and nitrate (NOx)
Time frame: 1 day
Urinary excretion of nitrite and nitrate (NOx)
Time frame: 1 day
Glomerular filtration rate
Time frame: 1 day
Proximal sodium transport (Estimated by lithium clearance)
Time frame: 1 day
Free water clearance
Time frame: 1 day
Urinary excretion of cyclic guanosine monophosphate (cGMP)
Time frame: 1 day
Urinary excretion of epithelial sodium channels (ENaC)
Time frame: 1 day
Urinary excretion of aquaporin 2 water channels (AQP2)
Time frame: 1 day
Plasma concentration of renin (PRC)
Time frame: 1 day
Plasma concentration of angiotensin II (ANG2)
Time frame: 1 day
Plasma concentration of aldosterone
Time frame: 1 day
Plasma concentration of atrial natriuretic peptide (ANP)
Time frame: 1 day
Plasma concentration of brain natriuretic peptide (BNP)
Time frame: 1 day
Plasma concentration of cyclic guanosine monophosphate (cGMP)
Time frame: 1 day
Plasma concentration of endothelin
Time frame: 1 day
Plasma concentration of vasopressin (AVP, ADH)
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2015.
- Derived from this study: PubMed 29065098Rosenbaek JB, Hornstrup BG, Jorgensen AN, Mortensen J, Pedersen EB, Bech JN. Effects of sodium nitrite on renal function and blood pressure in hypertensive vs. healthy study participants: a randomized, placebo-controlled, crossover study. J Hypertens. 2018 Mar;36(3):666-679. doi: 10.1097/HJH.0000000000001598.
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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.
Erling B Pedersen, MD, DMSc principal investigator
Holstebro Regional Hospital
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 Sodium nitrite and Sodium chloride in people with Hypertension, run by Erling Bjerregaard Pedersen at 1 site in Denmark.
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 5 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 19 Aug 2015. 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 Denmark. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jeppe B Rosenbaek, MD (+4578436585, jepros@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fractional urinary sodium excretion (FENa) (time frame: 1 day). 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 NCT02527837, 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 19 Aug 2015.