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Completed

NCT Number: NCT04755400

The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics

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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Vascular Diseases

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Godstrup Hospital

Herning, 7400, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-64 years
  • BMI 18,5-30
  • Normotensive
  • Women must use contraception

Exclusion criteria

  • 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
  • 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

Treatment and study plan

isotonic saline 9%

Other

1 Liter of Isotonic saline administered I.V.

Other names: Sodium Chloride 9%

Potassium nitrate

Dietary 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 Chloride

Dietary Supplement

24 mmol of Potassium nitrate is the placebo substance, that is ingested every morning for 4 days before and on the examination day.

Primary outcomes

  1. Glomerular filtration rate (GFR)

    Time frame: analysed right after each examination day. (day 1)

    mL/minute

Secondary outcomes

  1. Brachial blood pressure (BP)

    Time frame: analysed right after each examination day. (day 1)

    mmhg

  2. central blood pressure (cSBP)

    Time frame: analysed right after each examination day. (day 1)

    mmhg

  3. Heart rate

    Time frame: analysed right after each examination day. (day 1)

    beats pr. min.

  4. Pulse wave velocity (PWV)

    Time frame: analysed right after each examination day. (day 1)

    measured via Mobilograph

  5. Total vascular resistance (TVR)

    Time frame: analysed right after each examination day. (day 1)

    measured via Mobilograph

  6. Augmentation index (Aix@75)

    Time frame: analysed right after each examination day. (day 1)

    measured via Mobilograph

  7. Urinary excretions of aquaporin-2 (u-AQP2)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    ng/mmol crea

  8. Urinary excretions of epithelial sodium channels (u-ENaCγ)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    ng/mmol crea

  9. Urinary excretions of Na-Cl cotransporter (u-NCC).

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    ng/mmol crea

  10. plasma concentration of renin (PRC)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pg/mL

  11. plasma concentration of angiotensin II (p-AngII)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pg/mL

  12. plasma concentration of aldosterone (p-Aldo)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pmol/L

  13. plasma concentration of arginine vasopressin (p-AVP)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pg/mL

  14. plasma concentration of atrial natriuretic peptide (p-ANP)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pmol/L

  15. plasma concentration of brain natriuretic peptide (p-BNP).

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pmol/L

  16. plasma and urine levels of Nitrate (NO3)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    μmol/L

  17. plasma and urine levels of nitrite (NO2)

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    μmol/L

  18. plasma and urine levels of cyclic guanosine monophosphate (cGMP).

    Time frame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.

    pmol/mL

  19. Creatinine clearance (CrCl)

    Time frame: analysed right after each examination day. (day 1)

    mL/minute

  20. Urinary excretion rate of sodium (U-Na)

    Time frame: analysed right after each examination day. (day 1)

    mmol/min

  21. Urinary excretion rate of potassium(U-K)

    Time frame: analysed right after each examination day. (day 1)

    mmol/min

  22. Free water clearance (CH2O)

    Time frame: analysed right after each examination day. (day 1)

    mL/minute

  23. Fractional excretion of sodium (FENa)

    Time frame: analysed right after each examination day. (day 1)

    calculated into %

  24. Fractional excretion of potassium (FEK)

    Time frame: analysed right after each examination day. (day 1)

    calculated into %

  25. Urinary excretion rate of albumin (UAER)

    Time frame: analysed right after each examination day. (day 1)

    µg/min

Sponsors and collaborators

Lead sponsor

Frank Mose

Other

Collaborators

  • Herning Hospital

Registry information

Official study title

The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics, in a Randomized, Placebo Controlled, Crossed Over Study on Healthy Subjects.

Acronym: APNI

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Feb 16, 2021
Registry last updated
Feb 21, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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