Clinical trial NCT04755400: The Effect of Orally Administrated Nitrate on Renal Parameters and Systemic Haemodynamics
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Lead sponsor: Region MidtJylland Denmark
Sponsor class: OTHER
Collaborators: name: Herning Hospital
First posted: 2021-02-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: double-blinded, placebo-controlled, crossover study
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Glomerular filtration rate (GFR)
timeFrame: analysed right after each examination day. (day 1)
Secondary outcomes:
measure: Brachial blood pressure (BP)
timeFrame: analysed right after each examination day. (day 1)
measure: central blood pressure (cSBP)
timeFrame: analysed right after each examination day. (day 1)
measure: Heart rate
timeFrame: analysed right after each examination day. (day 1)
measure: Pulse wave velocity (PWV)
timeFrame: analysed right after each examination day. (day 1)
measure: Total vascular resistance (TVR)
timeFrame: analysed right after each examination day. (day 1)
measure: Augmentation index (Aix@75)
timeFrame: analysed right after each examination day. (day 1)
measure: Urinary excretions of aquaporin-2 (u-AQP2)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: Urinary excretions of epithelial sodium channels (u-ENaCγ)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: Urinary excretions of Na-Cl cotransporter (u-NCC).
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of renin (PRC)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of angiotensin II (p-AngII)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of aldosterone (p-Aldo)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of arginine vasopressin (p-AVP)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of atrial natriuretic peptide (p-ANP)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma concentration of brain natriuretic peptide (p-BNP).
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma and urine levels of Nitrate (NO3)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma and urine levels of nitrite (NO2)
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: plasma and urine levels of cyclic guanosine monophosphate (cGMP).
timeFrame: Centrifuged and hereafter frozen. Analyzed during the following 12 months.
measure: Creatinine clearance (CrCl)
timeFrame: analysed right after each examination day. (day 1)
measure: Urinary excretion rate of sodium (U-Na)
timeFrame: analysed right after each examination day. (day 1)
measure: Urinary excretion rate of potassium(U-K)
timeFrame: analysed right after each examination day. (day 1)
measure: Free water clearance (CH2O)
timeFrame: analysed right after each examination day. (day 1)
measure: Fractional excretion of sodium (FENa)
timeFrame: analysed right after each examination day. (day 1)
measure: Fractional excretion of potassium (FEK)
timeFrame: analysed right after each examination day. (day 1)
measure: Urinary excretion rate of albumin (UAER)
timeFrame: analysed right after each examination day. (day 1)
Other outcomes:
Locations:
city: Herning
country: Denmark
facility: Godstrup Hospital
Study officials:
affiliation: University of Aarhus
name: Jesper N Bech, Ph.D., M.D.
role: STUDY_DIRECTOR
References: