HealthyPhase 1NCT02078908
The Effect of Sodium Nitrite on Renal Function and Blood Pressure in Healthy Humans. A Dose-response Study
A Phase 1 study testing Sodium nitrite, 40 micrograms/kg/hour, Sodium nitrite, 120 micrograms/kg/hour and Sodium nitrite, 240 micrograms/kg/hour in people with Healthy, run by Erling Bjerregaard Pedersen at 1 site in Denmark.
Trial summary
The purpose of this study is to investigate the effect of different doses of sodium nitrite infusion in 12 healthy subjects. 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 more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Sodium nitrite, 40 micrograms/kg/hour, Sodium nitrite, 120 micrograms/kg/hour and Sodium nitrite, 240 micrograms/kg/hour
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2013to Jun 2014
- 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 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI 18,5-30 kg/m2
- Women must use safe contraception
Who cannot join
- Tobacco smoking, medicine or substance abuse
- Weekly consumption of more than 21 standard drinks of alcohol for men and 14 standard drinks of alcohol for women (1 danish standard drink equals 12 grams of alcohol)
- Medical treatment in the last 2 weeks except for contraception
- Pregnancy or nursing
- Diabetes mellitus
- estimated glomerular filtration rate (eGFR) < 60 ml/min
Show all 11Show fewer
- neoplasm
- clinically significant heart, lung, liver, kidney, metabolic og neurologic disease
- clinically significant findings in screening blood samples, urine sample or ECG
- Office blood pressure > 140/90 mmHg
- Blood donation within 1 month of the first day of investigation
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Medical Research, Regional Hospital Holstebro
Holstebro, 7500
About this study
Official title: The Effect of Sodium Nitrite on Renal Variables, Brachial and Central Blood Pressure in Healthy Humans. A Randomized, Cross Over, Placebo Controlled Dose-response Study
The purpose of this study is to investigate the effect of different doses of sodium nitrite infusion in 12 healthy subjects. 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.
Hypothesis
Sodium nitrite infusion
- increases urinary sodium excretion and renal filtration rate
- lowers blood pressure, central as well as peripheral
- affects vasoactive hormones
- it is possible to establish a dose that affects the renal function with only minor effect on the blood pressure.
Read the detailed description
Background:
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 newly designed wrist born device.
Hypothesis:
- Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR) in a dose related manner.
- 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
- It is possible to establish a dose that affects the renal variables with only minor effect on the blood pressure.
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:
12 healthy subjects are recruited in this randomised, cross over, placebo controlled, single-blinded study. Each subject will attend to four 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 one of three doses of sodium nitrite. During the four examination days each subject receives all treatments in random order.
Perspectives:
Knowledge regarding hemodynamic and renal dose-response relationship is essential, in order to carry out future planned studies of the nitrite-NO system, in hypertensive subjects and during simultaneous modulation of various enzyme systems, involved in the conversion of nitrite to NO. Increasing knowledge about the nitrite-NO system can contribute to changing the clinical practise of diagnostics and treatment of cardiovascular diseases.
- Conditions
- Healthy
- Being tested
- Sodium nitrite, 40 micrograms/kg/hour, Sodium nitrite, 120 micrograms/kg/hour, Sodium nitrite, 240 micrograms/kg/hour, Placebo
- Keywords
- Central blood pressure, Peripheral (brachial) blood pressure, Renal variables, Vasoactive hormones, Pharmacology, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium nitrite, 40 micrograms/kg/hourDrug
Also called NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0
Continuous 2 hour infusion of sodium nitrite, 40 micrograms/kg/hour
Sodium nitrite, 120 micrograms/kg/hourDrug
Also called NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0
Continuous 2 hour infusion of sodium nitrite, 120 micrograms/kg/hour
Sodium nitrite, 240 micrograms/kg/hourDrug
Also called NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0
Continuous 2 hour infusion of sodium nitrite, 240 micrograms/kg/hour
PlaceboDrug
Also called Sodium chloride
Continuous 2 hour infusion of sodium chloride, 25 ml/hour
| Study group | Role | What they receive |
|---|---|---|
| 40 micrograms sodium nitrite | Active comparator | Continuous 2 hour infusion of sodium nitrite, 40 micrograms/kg/hour Receives: Drug: Sodium nitrite, 40 micrograms/kg/hour |
| 120 micrograms sodium nitrite | Active comparator | Continuous 2 hour infusion of sodium nitrite, 120 micrograms/kg/hour Receives: Drug: Sodium nitrite, 120 micrograms/kg/hour |
| 240 micrograms sodium nitrite | Active comparator | Continuous 2 hour infusion of sodium nitrite, 240 micrograms/kg/hour Receives: Drug: Sodium nitrite, 240 micrograms/kg/hour |
| Placebo | Placebo comparator | Continuous 2 hour infusion of sodium chloride, 25 ml/hour Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional urinary sodium excretion
Measured: One day
Secondary outcomes (18)
Nitrite clearance
Measured: One day
Nitrate clearance
Measured: One day
Glomerular filtration rate
Measured by determent renal clearance of 51Cr-EDTA (51-chrome ethylenediaminetetraacetic acid) using constant infusing technique
Measured: One day
Proximal sodium transport
Proximal sodium transport is estimated by lithium clearance
Measured: One day
Free water clearance
Measured: One day
Urinary excretion of cyclic guanosine monophosphate (cGMP)
Measured: One day
Urinary excretion of epithelial sodium channels (ENaC)
Measured: One day
Urinary excretion of water channels (aquaporin-2)
Measured: One day
Plasma concentration of renin
Measured: One day
Plasma concentration of angiotensin 2
Measured: One day
Plasma concentration of aldosterone
Measured: One day
Plasma concentration of atrial natriuretic peptide (ANP)
Measured: One day
Plasma concentration of brain natriuretic peptide (BNP)
Measured: One day
Plasma concentration of cyclic guanosine monophosphate (cGMP)
Measured: One day
Plasma concentration of endothelin
Measured: One day
Plasma concentration of vasopressin (AVP, ADH)
Measured: One day
Peripheral (brachial) blood pressure
Measured by oscillometric sphygmomanometer, Omron 705IT, Omron Matsusaka CO. Ltd.
Measured: One day
Central aortic systolic blood pressure (CASP)
Estimated by tonometric pulse wave analysis. Device: BPro from HealthSTATS International, Singapore
Measured: One day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study startSep 2013
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- 12 participants (actual)
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
- Jesper N Bech, MD, PhD, Principal investigator, Regional Hospital Holstebro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078908
- Sponsor's protocol ID
- JBR-1-2013
- Other IDs
- 2013-002211-10
- Status last verified
- Oct 2014
- First submitted
- 19 Sep 2013
- Last updated
- 9 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sodium Nitrite on Renal Variables, Brachial and Central Blood Pressure in Healthy Humans. A Randomized, Cross Over, Placebo Controlled Dose-response Study
- ClinicalTrials.gov ID
- NCT02078908
- Acronym / sponsor ID
- JBR-1-2013
- Conditions
- Healthy
- Keywords
- Central blood pressure, Peripheral (brachial) blood pressure, Renal variables, Vasoactive hormones, Pharmacology, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Erling Bjerregaard PedersenUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 5 Mar 2014 (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 the effect of different doses of sodium nitrite infusion in 12 healthy subjects. 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.
Hypothesis
Sodium nitrite infusion
- increases urinary sodium excretion and renal filtration rate
- lowers blood pressure, central as well as peripheral
- affects vasoactive hormones
- it is possible to establish a dose that affects the renal function with only minor effect on the blood pressure.
Detailed description
Background:
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 newly designed wrist born device.
Hypothesis:
- Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR) in a dose related manner.
- 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
- It is possible to establish a dose that affects the renal variables with only minor effect on the blood pressure.
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:
12 healthy subjects are recruited in this randomised, cross over, placebo controlled, single-blinded study. Each subject will attend to four 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 one of three doses of sodium nitrite. During the four examination days each subject receives all treatments in random order.
Perspectives:
Knowledge regarding hemodynamic and renal dose-response relationship is essential, in order to carry out future planned studies of the nitrite-NO system, in hypertensive subjects and during simultaneous modulation of various enzyme systems, involved in the conversion of nitrite to NO. 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
- 4
| Arm | Type | Receives |
|---|---|---|
| 40 micrograms sodium nitrite | Active comparator | Drug: Sodium nitrite, 40 micrograms/kg/hourContinuous 2 hour infusion of sodium nitrite, 40 micrograms/kg/hour |
| 120 micrograms sodium nitrite | Active comparator | Drug: Sodium nitrite, 120 micrograms/kg/hourContinuous 2 hour infusion of sodium nitrite, 120 micrograms/kg/hour |
| 240 micrograms sodium nitrite | Active comparator | Drug: Sodium nitrite, 240 micrograms/kg/hourContinuous 2 hour infusion of sodium nitrite, 240 micrograms/kg/hour |
| Placebo | Placebo comparator | Drug: PlaceboContinuous 2 hour infusion of sodium chloride, 25 ml/hour |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- BMI 18,5-30 kg/m2
- Women must use safe contraception
Key exclusion criteria (11 listed)
- Tobacco smoking, medicine or substance abuse
- Weekly consumption of more than 21 standard drinks of alcohol for men and 14 standard drinks of alcohol for women (1 danish standard drink equals 12 grams of alcohol)
- Medical treatment in the last 2 weeks except for contraception
- Pregnancy or nursing
- Diabetes mellitus
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 nitrite, 40 micrograms/kg/hourAlso: NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0Continuous 2 hour infusion of sodium nitrite, 40 micrograms/kg/hour | Drug | 40 micrograms sodium nitrite |
| Sodium nitrite, 120 micrograms/kg/hourAlso: NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0Continuous 2 hour infusion of sodium nitrite, 120 micrograms/kg/hour | Drug | 120 micrograms sodium nitrite |
| Sodium nitrite, 240 micrograms/kg/hourAlso: NaNO2, ATC V03AB08, EV substance code: SUB15308MIG, CAS15 number: 7632-00-0Continuous 2 hour infusion of sodium nitrite, 240 micrograms/kg/hour | Drug | 240 micrograms sodium nitrite |
| PlaceboAlso: Sodium chlorideContinuous 2 hour infusion of sodium chloride, 25 ml/hour | Drug | Placebo |
Primary outcome
Fractional urinary sodium excretion
Time frame: One day
18 secondary outcomes
Nitrite clearance
Time frame: One day
Nitrate clearance
Time frame: One day
Glomerular filtration rate
Time frame: One day
Proximal sodium transport
Time frame: One day
Free water clearance
Time frame: One day
Urinary excretion of cyclic guanosine monophosphate (cGMP)
Time frame: One day
Urinary excretion of epithelial sodium channels (ENaC)
Time frame: One day
Urinary excretion of water channels (aquaporin-2)
Time frame: One day
Plasma concentration of renin
Time frame: One day
Plasma concentration of angiotensin 2
Time frame: One day
Plasma concentration of aldosterone
Time frame: One day
Plasma concentration of atrial natriuretic peptide (ANP)
Time frame: One day
Plasma concentration of brain natriuretic peptide (BNP)
Time frame: One day
Plasma concentration of cyclic guanosine monophosphate (cGMP)
Time frame: One day
Plasma concentration of endothelin
Time frame: One day
Plasma concentration of vasopressin (AVP, ADH)
Time frame: One day
Peripheral (brachial) blood pressure
Time frame: One day
Central aortic systolic blood pressure (CASP)
Time frame: One day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2014.
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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.
Jesper N Bech, MD, PhD principal investigator
Regional Hospital Holstebro
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, 40 micrograms/kg/hour, Sodium nitrite, 120 micrograms/kg/hour and Sodium nitrite, 240 micrograms/kg/hour in people with Healthy, 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 2 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: finished, as of the sponsor's last update on 9 Oct 2014. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Fractional urinary sodium excretion (time frame: One day). 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 9 Oct 2014.