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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 22, 2014