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

• ClinicalTrials.gov Identifier: NCT04755400
• Recruitment Status: Completed
• First Posted: February 16, 2021
• Last Update Posted: February 21, 2021
• Sponsor: Frank Mose
• Collaborator: Herning Hospital
• Information provided by (Responsible Party): Frank Mose, Region MidtJylland Denmark

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Other: isotonic saline 9%; Dietary Supplement: Potassium nitrate; Dietary Supplement: Potassium chloride	Not Applicable

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: double-blinded, placebo-controlled, crossover study
• Masking: Triple (Participant, Care Provider, Investigator)

Masking Description

The Hospital Pharmacy, Herning Hospital, generates the randomization list. A copy of the list is kept at the Medical Research department.

Patients are randomized to receive either potassium nitrate or placebo (Potassium chloride). The Hospital Pharmacy, Gødstrup Hospital, will blind both treatments.

• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: September 1, 2018
• Actual Primary Completion Date: March 15, 2020
• Actual Study Completion Date: March 15, 2020

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Glomerular filtration rate (GFR) [ Time Frame: analysed right after each examination day. (day 1) ]
   mL/minute

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Denmark

Godstrup Hospital

Herning, Denmark, 7400

Sponsors and Collaborators

Frank Mose

Herning Hospital

Investigators

• Study Director: Jesper N Bech, Ph.D., M.D.; University of Aarhus

More Information

• Responsible Party: Frank Mose, Associate professor, Region MidtJylland Denmark
• ClinicalTrials.gov Identifier: NCT04755400
• Other Study ID Numbers: AMH-1-2016
• First Posted: February 16, 2021
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases