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

Hypertension Clinical Trial

— APNI  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04755400
• Other study ID #: AMH-1-2016
• Status: Completed
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: March 15, 2020

Study information

• Verified date: February 2021
• Source: Region MidtJylland Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 15, 2020
• Est. primary completion date: March 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Other:
• isotonic saline 9%
1 Liter of Isotonic saline administered I.V.

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

Locations

Country	Name	City	State
Denmark	Godstrup Hospital	Herning

Sponsors (2)

Lead Sponsor	Collaborator
Frank Mose	Herning Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glomerular filtration rate (GFR)	mL/minute	analysed right after each examination day. (day 1)
Secondary	Brachial blood pressure (BP)	mmhg	analysed right after each examination day. (day 1)
Secondary	central blood pressure (cSBP)	mmhg	analysed right after each examination day. (day 1)
Secondary	Heart rate	beats pr. min.	analysed right after each examination day. (day 1)
Secondary	Pulse wave velocity (PWV)	measured via Mobilograph	analysed right after each examination day. (day 1)
Secondary	Total vascular resistance (TVR)	measured via Mobilograph	analysed right after each examination day. (day 1)
Secondary	Augmentation index (Aix@75)	measured via Mobilograph	analysed right after each examination day. (day 1)
Secondary	Urinary excretions of aquaporin-2 (u-AQP2)	ng/mmol crea	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	Urinary excretions of epithelial sodium channels (u-ENaC?)	ng/mmol crea	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	Urinary excretions of Na-Cl cotransporter (u-NCC).	ng/mmol crea	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of renin (PRC)	pg/mL	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of angiotensin II (p-AngII)	pg/mL	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of aldosterone (p-Aldo)	pmol/L	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of arginine vasopressin (p-AVP)	pg/mL	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of atrial natriuretic peptide (p-ANP)	pmol/L	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma concentration of brain natriuretic peptide (p-BNP).	pmol/L	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma and urine levels of Nitrate (NO3)	µmol/L	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma and urine levels of nitrite (NO2)	µmol/L	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	plasma and urine levels of cyclic guanosine monophosphate (cGMP).	pmol/mL	Centrifuged and hereafter frozen. Analyzed during the following 12 months.
Secondary	Creatinine clearance (CrCl)	mL/minute	analysed right after each examination day. (day 1)
Secondary	Urinary excretion rate of sodium (U-Na)	mmol/min	analysed right after each examination day. (day 1)
Secondary	Urinary excretion rate of potassium(U-K)	mmol/min	analysed right after each examination day. (day 1)
Secondary	Free water clearance (CH2O)	mL/minute	analysed right after each examination day. (day 1)
Secondary	Fractional excretion of sodium (FENa)	calculated into %	analysed right after each examination day. (day 1)
Secondary	Fractional excretion of potassium (FEK)	calculated into %	analysed right after each examination day. (day 1)
Secondary	Urinary excretion rate of albumin (UAER)	µg/min	analysed right after each examination day. (day 1)