L-NMMA Dose-response Study in Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: NG-monomethyl-L-arginine (L-NMMA)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Holstebro, Denmark, 7500
    • Departments of Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Systolic blood pressure	6 hours

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Regional Hospital Holstebro
• Investigators: Principal Investigator: Thomas Larsen, M.D., Departments of Medical Research, Holstebro Hospital; Principal Investigator: Frank H Christensen, M.D., Departments of Medical Research, Holstebro Hospital; Principal Investigator: Erling B Pedersen, Dr.med., Departments of Medical Research, Holstebro Hospital; Principal Investigator: Jesper N Bech, Ph.d., Departments of Medical Research, Holstebro Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): February 21, 2011
• Last Update Submitted That Met QC Criteria: February 18, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: blood pressure; healthy subjects; pulse wave velocity; arterial stiffness; dose-response; GFR; augmentation index; L-NMMA
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; omega-N-Methylarginine
• Other Study ID Numbers: EBP.FHC.1.2009; 2009-017001-11 (EudraCT Number)