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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Other: isotonic saline 9%; Dietary supplement: Potassium nitrate; Dietary supplement: Potassium chloride

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Herning, Denmark, 7400
    • Godstrup Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Potassium Nitrate; 4 days treatment with 24 mmol potassium nitrate capsules	Other: isotonic saline 9%; 1 Liter of Isotonic saline administered I.V.; Other Names: Sodium Chloride 9%; 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.
Placebo Comparator: Potassium Chloride; 4 days treatment 24 mmol potassium chloride capsules	Other: isotonic saline 9%; 1 Liter of Isotonic saline administered I.V.; Other Names: Sodium Chloride 9%; Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glomerular filtration rate (GFR)	mL/minute	analysed right after each examination day. (day 1)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Frank Mose
• Collaborators: Herning Hospital
• Investigators: Study Director: Jesper N Bech, Ph.D., M.D., University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): March 15, 2020
• Study Completion (Actual): March 15, 2020

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: AMH-1-2016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No