L-NMMA Dose-response Study in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
Regional Hospital Holstebro
ClinicalTrials.gov Identifier:
NCT01070940
First received: February 17, 2010
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: NG-monomethyl-L-arginine (L-NMMA)
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Official Title: L-NMMA's Effect on Renal and Cardiovascular Variables in Healthy Subjects. A Randomized, Placebo-controlled Crossover Study.

Resource links provided by NLM:


Further study details as provided by Regional Hospital Holstebro:

Primary Outcome Measures:
  • Systolic blood pressure [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • GFR [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Arterial Stiffness [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Fractional excretion of sodium [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Fractional excretion of potassium [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Plasma renin concentration [ Time Frame: 6 hour ] [ Designated as safety issue: No ]
  • Plasma angiotensin II [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Plasma aldosterone [ Time Frame: 6 hour ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: February 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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)
6 mg/kg IV priming dose + 4 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

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01070940

Locations
Denmark
Departments of Medical Research
Holstebro, Denmark, 7500
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Thomas Larsen, M.D., Departments of Medical Research, Holstebro Hospital
ClinicalTrials.gov Identifier: NCT01070940     History of Changes
Other Study ID Numbers: EBP.FHC.1.2009, 2009-017001-11
Study First Received: February 17, 2010
Last Updated: February 18, 2011
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Regional Hospital Holstebro:
L-NMMA
blood pressure
arterial stiffness
pulse wave velocity
augmentation index
dose-response
healthy subjects
GFR

Additional relevant MeSH terms:
Omega-N-Methylarginine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014