L-NMMA Dose-response Study in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of different levels of nitric oxide inhibition on blood pressure and arterial stiffness in healthy subjects. L-NMMA, an inhibitor of the nitric oxide synthase, is administered as bolus injection followed by continuous infusion, and is expected to raise blood pressure and arterial stiffness according to L-NMMA dose.

Official Title
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L-NMMA's Effect on Renal and Cardiovascular Variables in Healthy Subjects. A Randomized, Placebo-controlled Crossover Study.

Conditions
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Healthy

Intervention / Treatment
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* Drug: NG-monomethyl-L-arginine (L-NMMA)
* Drug: NG-monomethyl-L-arginine (L-NMMA)
* Drug: NG-monomethyl-L-arginine (L-NMMA)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Age 18-35 years BMI 18.5-30.0 Exclusion Criteria: Tobacco or illicit drug use Current use of any prescription or non-prescription drugs Alcohol abuse History of heart failure, lever failure, chronic kidney disease or cerebral insult Diabetes Clinical or paraclinical signs of infection Pathologic ECG Ambulatory blood pressure >140/90 mmHg Abnormal blood or urin screening tests

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Isotonic saline infusion<br> | Drug: Placebo<br>* Isotonic saline solution IV priming dose + IV infusion for 1 hour<br>|
| Active Comparator: Intravenous L-NMMA dose 2<br> | Drug: NG-monomethyl-L-arginine (L-NMMA)<br>* 4.5 mg/kg IV priming dose + 3 mg/kg/hr IV infusion for 1 hour<br>|
| Active Comparator: Intravenous L-NMMA dose 3<br> | Drug: NG-monomethyl-L-arginine (L-NMMA)<br>* 6 mg/kg IV priming dose + 4 mg/kg/hr IV infusion for 1 hour<br>|
| Active Comparator: Intravenous L-NMMA dose 1<br> | Drug: NG-monomethyl-L-arginine (L-NMMA)<br>* 3 mg/kg IV priming dose + 2 mg/kg/hr IV infusion for 1 hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure |  | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GFR |  | 6 hours | 
| Arterial Stiffness |  | 6 hours | 
| Fractional excretion of sodium |  | 6 hours | 
| Fractional excretion of potassium |  | 6 hours | 
| Plasma renin concentration |  | 6 hour | 
| Plasma angiotensin II |  | 6 hours | 
| Plasma aldosterone |  | 6 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L-NMMA, blood pressure, arterial stiffness, pulse wave velocity, augmentation index, dose-response, healthy subjects, GFR