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

NCT ID: NCT02527837

Last Updated: 2015-08-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-10-31

Brief 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.

Detailed 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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Sodium nitrite

Sodium nitrite, 240 micrograms/kg/hour for 2 hours

Group Type: ACTIVE_COMPARATOR

Sodium nitrite

Intervention Type: DRUG

Sodium nitrite, 240 micrograms/kg/hour for 2 hours

Placebo

Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours

Group Type: PLACEBO_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours

Interventions

Sodium nitrite

Sodium nitrite, 240 micrograms/kg/hour for 2 hours

Intervention Type: DRUG

Sodium chloride

Sodium chloride, isotonic 0.9%, 25 ml/hour for 2 hours

Intervention Type: DRUG

Other Intervention Names

NaNO2; NaCl

Eligibility Criteria

Inclusion Criteria

• 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

• BMI 18.5-30.0
• Women of childbearing potential must use safe contraception

Exclusion Criteria

• 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

• 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Erling Bjerregaard Pedersen

OTHER

Sponsor Role: lead

Responsible Party

Erling Bjerregaard Pedersen

Chief physician, professor, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Erling B Pedersen, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Holstebro Regional Hospital

Locations

Department of Medical Research and Medicine, Holstebro Regional Hospital

Holstebro, Holstebro, Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jeppe B Rosenbaek, MD

Role: CONTACT

jepros@rm.dk

+4578436585

Erling B Pedersen, MD, DMSc

Role: CONTACT

ebp@dadlnet.dk

+4578436840

Facility Contacts

Jeppe B Rosenbaek, MD

Role: primary

jepros@rm.dk

+4578436585

References

Rosenbaek JB, Hornstrup BG, Jorgensen AN, Mortensen J, Pedersen EB, Bech JN. Effects of sodium nitrite on renal function and blood pressure in hypertensive vs. healthy study participants: a randomized, placebo-controlled, crossover study. J Hypertens. 2018 Mar;36(3):666-679. doi: 10.1097/HJH.0000000000001598.

Reference Type: DERIVED

PMID: 29065098 (View on PubMed)

Other Identifiers

JBR-1-2014

Identifier Type: -

Identifier Source: org_study_id