The Effect of Sodium Nitrite on Renal Function and Blood Pressure in Hypertensive Versus Healthy Subjects

Hypertension Clinical Trial

— HYCA  

Official title:

The Effect of Sodium Nitrite Infusion on Renal Variables, Peripheral and Central Blood Pressure in Hypertensive Versus Normotensive Subjects in a Randomised, Placebo Controlled, Cross Over, Case-control Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02527837
• Other study ID #: JBR-1-2014
• Status: Recruiting
• Phase: Phase 1
• First received: February 18, 2015
• Last updated: August 17, 2015
• Start date: May 2015
• Est. completion date: October 2016

Study information

• Verified date: February 2015
• Source: Regional Hospital Holstebro
• Contact: Jeppe B Rosenbaek, MD
• Phone: +4578436585
• Email: jepros[@]rm.dk
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate how the effect of infused sodium nitrite differs in hypertensives compared to healthy age and sex matched controls. The effects on renal handling of nitrite, nitrate, sodium and water, plasma concentrations of vasoactive hormones, peripheral (brachial) and central blood pressure will be evaluated.

Description:

Nitric oxide (NO) is an important vasodilating molecule with a very complex biochemistry and metabolism. NO is classically synthesized from L-arginin by endothelial nitric oxide synthase (eNOS) located in the endothelial cell lining. Several chronic cardiovascular diseases such as hypertension, chronic kidney disease and diabetes are accompanied by endothelial dysfunction and hence diminished synthesis of NO. NO is a very reactive molecule and direct investigation of its function are limited and it has mainly been investigated by inhibition of eNOS. Recent research has shown that sodium nitrite is readily converted to NO by enzymes in vivo. The effects of sodium nitrite on renal variables, vasoactive hormones and central blood pressure are previously unexamined. It is now possible to achieve serial estimations of the central aortic systolic pressure (CASP) by a wrist born device.

Hypothesis:

1. Sodium nitrite infusion increases the urinary sodium excretion and glomerular filtration rate (GFR)

2. Sodium nitrite infusion increases plasma levels of nitrite, nitrate, NO and cyclic guanosine monophosphate (cGMP)

3. Sodium nitrite infusion lowers the peripheral and central blood pressure

4. Renal clearance of nitrite is constant and not dose dependent

5. Sodium nitrite infusion affects vasoactive hormones

6. The hemodynamic and renal effects is more pronounced in hypertensives as compared to healthy controls.

Purpose:

The purpose of this study is to investigate the effects of sodium nitrite infusion on

1. Renal handling of nitrite, nitrate, sodium and water

2. Plasma concentrations of vasoactive hormones

3. Peripheral (brachial) blood pressure and CASP

Design:

15 hypertensive subjects and 15 healthy, age and sex matched controls is recruited. Each subject will attend to two examination days. Four days prior to each examination day subjects are given a standardized diet with a low level of nitrate and nitrite. On the evening before the examination day the subjects take a single dose of lithium carbonate 300 mg in order to measure lithium clearance. On the examination days subjects are receiving a two hour infusion of either placebo (isotonic sodium chloride) or sodium nitrite. During the two examination days each subject receives both treatments in random order.

Perspectives:

Increasing knowledge about the nitrite-NO system can contribute to changing the clinical practise of diagnostics and treatment of cardiovascular diseases.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria (subjects with hypertension):

• BMI 18.5-30.0

• Ambulatory daytime blood pressure >135 mmHg systolic and/or >85 mmHg diastolic

• Women of childbearing potential must use safe contraception

Exclusion Criteria (subjects with hypertension):

• Tobacco smoking, medicine or substance abuse

• Weekly consumption of more than 14 units (12 g alcohol per unit) for women and 21 units for men

• Pregnancy or nursing

• Neoplasia

• Clinically significant heart, lung, liver, kidney, metabolic or neurologic disease

• Albuminuria > 300 mg/L

• Renography with signs of renal artery stenosis or hydronephrosis

• Clinically signs of secondary hypertension

• Clinically significant hypokalemia

• Clinically significant anemia

• Estimated glomerular filtration rate (eGFR) < 60 ml/min

• Clinically significant findings in screening blood samples, urine sample or ECG

• Persistent office blood pressure > 170/105 mmHg on the maximum dose of amlodipine (10 mg daily)

• Unacceptable symptoms of elevated blood pressure

• Unacceptable side effects of amlodipine

Inclusion Criteria (healthy normotensive subjects):

• BMI 18.5-30.0

• Women of childbearing potential must use safe contraception

Exclusion Criteria (healthy normotensive subjects):

• Tobacco smoking, medicine or substance abuse

• Weekly consumption of more than 14 units (12 g alcohol per unit) for women and 21 units for men

• Medical treatment 2 weeks prior to each examination day, except for contraception

• Pregnancy or nursing

• Neoplasia

• Clinically significant heart, lung, liver, kidney, metabolic or neurologic disease

• Clinically significant albuminuria

• Clinically significant anemia

• Estimated glomerular filtration rate (eGFR) < 60 ml/min

• Clinically significant findings in screening blood samples, urine sample or ECG

• Ambulatory daytime blood pressure >135/85 mmHg

• Blood donation within 1 month of the first examination day

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Sodium nitrite
Sodium nitrite, 240 micrograms/kg/hour for 2 hours
• Sodium chloride
Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours

Locations

Country	Name	City	State
Denmark	Department of Medical Research and Medicine, Holstebro Regional Hospital	Holstebro

Sponsors (1)

Lead Sponsor	Collaborator
Erling Bjerregaard Pedersen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fractional urinary sodium excretion (FENa)		1 day	No
Secondary	Peripheral (brachial) blood pressure	Measured by oscillometric sphygmomanometer	1 day	Yes
Secondary	Central aortic systolic blood pressure (CASP)	Measured by tonometric pulse wave analysis. Device BPro from HealthSTATS international, Singapore	1 day	No
Secondary	Plasma concentration of nitrite and nitrate (NOx)		1 day	No
Secondary	Urinary excretion of nitrite and nitrate (NOx)		1 day	No
Secondary	Glomerular filtration rate		1 day	No
Secondary	Proximal sodium transport (Estimated by lithium clearance)	Estimated by lithium clearance	1 day	No
Secondary	Free water clearance		1 day	No
Secondary	Urinary excretion of cyclic guanosine monophosphate (cGMP)		1 day	No
Secondary	Urinary excretion of epithelial sodium channels (ENaC)		1 day	No
Secondary	Urinary excretion of aquaporin 2 water channels (AQP2)		1 day	No
Secondary	Plasma concentration of renin (PRC)		1 day	No
Secondary	Plasma concentration of angiotensin II (ANG2)		1 day	No
Secondary	Plasma concentration of aldosterone		1 day	No
Secondary	Plasma concentration of atrial natriuretic peptide (ANP)		1 day	No
Secondary	Plasma concentration of brain natriuretic peptide (BNP)		1 day	No
Secondary	Plasma concentration of cyclic guanosine monophosphate (cGMP)		1 day	No
Secondary	Plasma concentration of endothelin		1 day	No
Secondary	Plasma concentration of vasopressin (AVP, ADH)		1 day	No