HypertensionAPNINCT04755400
The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics
A study testing isotonic saline 9%, Potassium nitrate and Potassium chloride in people with Hypertension, run by Frank Mose at 1 site in Denmark.
Trial summary
Treatment with nitrate has shown to lower blood pressure in both healthy subjects and hypertensive patients.Beside this nitrate have also shown to decrease arterial stiffness and improve endothelial function.But the effect of nitrate on renal blood flow, kidney function, water and salt balance and vasoactive hormones… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- isotonic saline 9%, Potassium nitrate and Potassium chloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2018to 15 Mar 2020
- Phase
- Interventional
- 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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-64 years
- BMI 18,5-30
- Normotensive
- Women must use contraception
Who cannot join
- Tobacco smoking (Non-smokers in more than 3 months can be included)
- Medicine- or drug abuse
- Alcohol abuse >7 units for women >14 units for men
- Medical treatment (over the counter medication will evaluated whether or not it is grounds for exclusion) within 2 weeks before the trail period starts except contraception.
- Pregnancy or nursing
- Neoplastic disorders
Show all 9Show fewer
- Significant clinical signs of heart-, lung-, liver-, kidney-, endocrine- or brain disorders
- Clinically significant abnormal findings in screening blood samples, urine sample or ECG - Donation of blood within 1 month of the first day of investigation.
- Allergy against compounds in investigational medicine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics, in a Randomized, Placebo Controlled, Crossed Over Study on Healthy Subjects.
Treatment with nitrate has shown to lower blood pressure in both healthy subjects and hypertensive patients.Beside this nitrate have also shown to decrease arterial stiffness and improve endothelial function.But the effect of nitrate on renal blood flow, kidney function, water and salt balance and vasoactive hormones is still unclear.
Therefore, the purpose of this study is to investigate the effect of orally administered nitrate on these parameters.
This will be done in a double-blinded, placebo-controlled, crossover study. 20 healthy subjects will be treated, in a randomized order, with both potassium nitrate and placebo separated by at least 4 weeks wash-out.
Read the detailed description
Inorganic nitrate reduces blood pressure and improves endothelial function in both healthy subjects and hypertensive patients.
This effect is thought to be caused through bioconversion to nitric oxide. Thus improving risk factors of cardiovascular decease by increasing vasodilatation, salt regulation and vasoactive hormones.The purpose of this study is to investigate the effect of inorganic nitrate on kidney function, hormones and circulation, which is still unknown.
The effect of 4 days treatment with 24 mmol potassium nitrate capsules on heart rate, blood pressure, vasoactive hormones and urinary excretion of sodium and water will be measured in a randomized, placebo controlled, double blinded, crossover study in 20 healthy subjects. Each subject attends 2x2 examination days at least 4 weeks apart. The examination days are divided into 8 clearance periods of 30 min. each. The first 3 are baseline periods and in period 4 1 Liter of saline is administered to detect any difference in renal parameters after NaCl load.
If inorganic nitrate supplementation is found to lower blood pressure in addition to favorable renal effects, it could lead to changes in the general treatment of high blood pressure and cardiovascular disease.
- Conditions
- Hypertension
- Being tested
- isotonic saline 9%, Potassium nitrate, Potassium chloride
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isotonic saline 9%Other
Also called Sodium Chloride 9%
1 Liter of Isotonic saline administered I.V.
Potassium nitrateDietary supplement
24 mmol of Potassium nitrate is the active comparator substance, that is ingested every morning for 4 days before and on the examination day.
Potassium chlorideDietary supplement
24 mmol of Potassium nitrate is the placebo substance, that is ingested every morning for 4 days before and on the examination day.
| Study group | Role | What they receive |
|---|---|---|
| Potassium Nitrate | Active comparator | 4 days treatment with 24 mmol potassium nitrate capsules Receives: Other: isotonic saline 9%; Dietary Supplement: Potassium nitrate |
| Potassium Chloride | Placebo comparator | 4 days treatment 24 mmol potassium chloride capsules Receives: Other: isotonic saline 9%; Dietary Supplement: Potassium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular filtration rate (GFR)
mL/minute
Measured: analysed right after each examination day. (day 1)
Secondary outcomes (25)
Brachial blood pressure (BP)
mmhg
Measured: analysed right after each examination day. (day 1)
central blood pressure (cSBP)
mmhg
Measured: analysed right after each examination day. (day 1)
Heart rate
beats pr. min.
Measured: analysed right after each examination day. (day 1)
Pulse wave velocity (PWV)
measured via Mobilograph
Measured: analysed right after each examination day. (day 1)
Total vascular resistance (TVR)
measured via Mobilograph
Measured: analysed right after each examination day. (day 1)
Augmentation index (Aix@75)
measured via Mobilograph
Measured: analysed right after each examination day. (day 1)
Urinary excretions of aquaporin-2 (u-AQP2)
ng/mmol crea
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Urinary excretions of epithelial sodium channels (u-ENaCγ)
ng/mmol crea
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Urinary excretions of Na-Cl cotransporter (u-NCC).
ng/mmol crea
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of renin (PRC)
pg/mL
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of angiotensin II (p-AngII)
pg/mL
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of aldosterone (p-Aldo)
pmol/L
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of arginine vasopressin (p-AVP)
pg/mL
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of atrial natriuretic peptide (p-ANP)
pmol/L
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of brain natriuretic peptide (p-BNP).
pmol/L
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of Nitrate (NO3)
μmol/L
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of nitrite (NO2)
μmol/L
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of cyclic guanosine monophosphate (cGMP).
pmol/mL
Measured: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Creatinine clearance (CrCl)
mL/minute
Measured: analysed right after each examination day. (day 1)
Urinary excretion rate of sodium (U-Na)
mmol/min
Measured: analysed right after each examination day. (day 1)
Urinary excretion rate of potassium(U-K)
mmol/min
Measured: analysed right after each examination day. (day 1)
Free water clearance (CH2O)
mL/minute
Measured: analysed right after each examination day. (day 1)
Fractional excretion of sodium (FENa)
calculated into %
Measured: analysed right after each examination day. (day 1)
Fractional excretion of potassium (FEK)
calculated into %
Measured: analysed right after each examination day. (day 1)
Urinary excretion rate of albumin (UAER)
µg/min
Measured: analysed right after each examination day. (day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2021
- Study start1 Sep 2018
- Primary completion15 Mar 2020
- Study completion15 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- double-blinded, placebo-controlled, crossover study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Frank Mose
- Sponsor type
- University, hospital or other
- Collaborators
- Herning Hospital
- Responsible party
- Sponsor-investigator, Frank Mose, Region MidtJylland Denmark
- Investigators
- Jesper N Bech, Ph.D., M.D., Study director, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04755400
- Sponsor's protocol ID
- AMH-1-2016
- Acronym
- APNI
- Status last verified
- Feb 2021
- First submitted
- 3 Feb 2021
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics, in a Randomized, Placebo Controlled, Crossed Over Study on Healthy Subjects.
- ClinicalTrials.gov ID
- NCT04755400
- Acronym / sponsor ID
- APNI / AMH-1-2016
- Conditions
- Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Frank MoseUniversity, hospital or other
- Collaborators
- Herning Hospital
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 15 Mar 2020 (actual)
- Study completion
- 15 Mar 2020 (actual)
- First posted
- 16 Feb 2021 (actual)
- 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.
Treatment with nitrate has shown to lower blood pressure in both healthy subjects and hypertensive patients.Beside this nitrate have also shown to decrease arterial stiffness and improve endothelial function.But the effect of nitrate on renal blood flow, kidney function, water and salt balance and vasoactive hormones is still unclear.
Therefore, the purpose of this study is to investigate the effect of orally administered nitrate on these parameters.
This will be done in a double-blinded, placebo-controlled, crossover study. 20 healthy subjects will be treated, in a randomized order, with both potassium nitrate and placebo separated by at least 4 weeks wash-out.
Detailed description
Inorganic nitrate reduces blood pressure and improves endothelial function in both healthy subjects and hypertensive patients.
This effect is thought to be caused through bioconversion to nitric oxide. Thus improving risk factors of cardiovascular decease by increasing vasodilatation, salt regulation and vasoactive hormones.The purpose of this study is to investigate the effect of inorganic nitrate on kidney function, hormones and circulation, which is still unknown.
The effect of 4 days treatment with 24 mmol potassium nitrate capsules on heart rate, blood pressure, vasoactive hormones and urinary excretion of sodium and water will be measured in a randomized, placebo controlled, double blinded, crossover study in 20 healthy subjects. Each subject attends 2x2 examination days at least 4 weeks apart. The examination days are divided into 8 clearance periods of 30 min. each. The first 3 are baseline periods and in period 4 1 Liter of saline is administered to detect any difference in renal parameters after NaCl load.
If inorganic nitrate supplementation is found to lower blood pressure in addition to favorable renal effects, it could lead to changes in the general treatment of high blood pressure and cardiovascular disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- double-blinded, placebo-controlled, crossover study
| Arm | Type | Receives |
|---|---|---|
| Potassium Nitrate | Active comparator | Other: isotonic saline 9%, Dietary Supplement: Potassium nitrate4 days treatment with 24 mmol potassium nitrate capsules |
| Potassium Chloride | Placebo comparator | Other: isotonic saline 9%, Dietary Supplement: Potassium chloride4 days treatment 24 mmol potassium chloride capsules |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 18-64 years
- BMI 18,5-30
- Normotensive
- Women must use contraception
Key exclusion criteria (9 listed)
- Tobacco smoking (Non-smokers in more than 3 months can be included)
- Medicine- or drug abuse
- Alcohol abuse >7 units for women >14 units for men
- Medical treatment (over the counter medication will evaluated whether or not it is grounds for exclusion) within 2 weeks before the trail period starts except contraception.
- Pregnancy or nursing
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 |
|---|---|---|
| isotonic saline 9%Also: Sodium Chloride 9%1 Liter of Isotonic saline administered I.V. | Other | Potassium Chloride, Potassium Nitrate |
| Potassium nitrate24 mmol of Potassium nitrate is the active comparator substance, that is ingested every morning for 4 days before and on the examination day. | Dietary supplement | Potassium Nitrate |
| Potassium chloride24 mmol of Potassium nitrate is the placebo substance, that is ingested every morning for 4 days before and on the examination day. | Dietary supplement | Potassium Chloride |
Primary outcome
Glomerular filtration rate (GFR)
Time frame: analysed right after each examination day. (day 1)
mL/minute
25 secondary outcomes
Brachial blood pressure (BP)
Time frame: analysed right after each examination day. (day 1)
central blood pressure (cSBP)
Time frame: analysed right after each examination day. (day 1)
Heart rate
Time frame: analysed right after each examination day. (day 1)
Pulse wave velocity (PWV)
Time frame: analysed right after each examination day. (day 1)
Total vascular resistance (TVR)
Time frame: analysed right after each examination day. (day 1)
Augmentation index (Aix@75)
Time frame: analysed right after each examination day. (day 1)
Urinary excretions of aquaporin-2 (u-AQP2)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Urinary excretions of epithelial sodium channels (u-ENaCγ)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Urinary excretions of Na-Cl cotransporter (u-NCC).
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of renin (PRC)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of angiotensin II (p-AngII)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of aldosterone (p-Aldo)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of arginine vasopressin (p-AVP)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of atrial natriuretic peptide (p-ANP)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma concentration of brain natriuretic peptide (p-BNP).
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of Nitrate (NO3)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of nitrite (NO2)
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
plasma and urine levels of cyclic guanosine monophosphate (cGMP).
Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Creatinine clearance (CrCl)
Time frame: analysed right after each examination day. (day 1)
Urinary excretion rate of sodium (U-Na)
Time frame: analysed right after each examination day. (day 1)
Urinary excretion rate of potassium(U-K)
Time frame: analysed right after each examination day. (day 1)
Free water clearance (CH2O)
Time frame: analysed right after each examination day. (day 1)
Fractional excretion of sodium (FENa)
Time frame: analysed right after each examination day. (day 1)
Fractional excretion of potassium (FEK)
Time frame: analysed right after each examination day. (day 1)
Urinary excretion rate of albumin (UAER)
Time frame: analysed right after each examination day. (day 1)
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 21 Feb 2021.
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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, Ph.D., M.D. study director
University of Aarhus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing isotonic saline 9%, Potassium nitrate and Potassium chloride in people with Hypertension, run by Frank Mose 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 4 inclusion and 9 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 21 Feb 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 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.
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?
Glomerular filtration rate (GFR) (time frame: analysed right after each examination day. (day 1)). 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 21 Feb 2021.