The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man (STAR)

This study has been completed.
Sponsor:
Information provided by:
Regional Hospital Holstebro
ClinicalTrials.gov Identifier:
NCT01214746
First received: May 18, 2010
Last updated: August 15, 2011
Last verified: August 2011
  Purpose

It has been documented that statin reduce mortality and morbidity in patients with cardiovascular disease. This effect can partly be related to a reduction in cholesterol levels in blood. Nitric oxide (NO) production is reduced in several chronic diseases such as nephropathy, diabetes and hypertension. The purpose of this study is to investigate the effect of Atorvastatin treatment on the NO-system measuring renal and cardiovascular variables in healthy man.


Condition Intervention Phase
Cardiovascular Diseases
Nephropathy
Drug: Placebo
Drug: Atorvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man

Resource links provided by NLM:


Further study details as provided by Regional Hospital Holstebro:

Primary Outcome Measures:
  • Fractional excretion of sodium [ Time Frame: 5 days treatment ] [ Designated as safety issue: No ]
    Sodium excretion measured before, during and after L-NMMA infusion


Secondary Outcome Measures:
  • Systolic blood pressure (SBP) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Pulse wave velocity [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • plasma renin concentration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Augmentation index (AI) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Diastolic blood pressure [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Plasma aldosterone concentration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Plasma and urinary albumin concentration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Urinary excretion of aquaporin-2 [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • plasma atrial natriuretic peptide concentration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Plasma brain natriuretic peptide concentration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC) [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: May 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
1 tablet Unikalk 1 time pr day for 5 days
Other Name: Unikalk
Active Comparator: Atorvastatin Drug: Atorvastatin
Zarator, 80 mg pr day for 5 days
Other Name: Zarator

Detailed Description:

Subjects will be examined on two examination days. 4 days prior to each examination day subjects are treated with either atorvastatin or placebo. During treatment periods subject are given a standardized diet.

On the examination days subject are given L-NMMA(L-NG-monomethyl Arginine citrate), a NO inhibitor, 6 mg bolus infusion followed by continuous 4 mg/kg/hr infusion for 1 hour. Renal function, central hemodynamic and vasoactive hormones are evaluated prior, during and after L-NMMA infusion.

Renal function is measured by renal clearance of 51Cr-EDTA and urinary sodium, potassium and albumin concentration. Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC)will be measured to evaluate channel activity in the nephron.

Central blood pressure, pulse wave analysis, and augmentation index are measured using SphygmoCor® from Atcor.

The vasoactive hormones aldosterone, renin, angiotensin II, atrial natriuretic peptide (ANP), brain natriuretic (BNP) and endothelin is measured in plasma

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women, age 18-40 years
  • Body Mass Index (BMI) 18,5-30 kg/m2

Exclusion Criteria:

  • Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)
  • Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
  • Neoplastic disease
  • Alcohol abuse,
  • Drug abuse
  • Medical treatment except oral anticontraceptive
  • Smoking
  • Pregnancy or
  • Abnormal blood and urine sample
  • Abnormal ECG
  • Blood donation within a month before examination
  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: NCT01214746

Locations
Denmark
Medicinsk Forskning, Regionshospitalet Holstebro
Holstebro, Denmark, 7500
Sponsors and Collaborators
Regional Hospital Holstebro
Investigators
Principal Investigator: Frank H Christensen, MD Medicinsk Forskning
  More Information

No publications provided

Responsible Party: MD Frank Holden Christensen, Department of Medical Research, Regionshospitalet Holstebro
ClinicalTrials.gov Identifier: NCT01214746     History of Changes
Other Study ID Numbers: EBP-FHC-2010-1
Study First Received: May 18, 2010
Last Updated: August 15, 2011
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Regional Hospital Holstebro:
Statin
L-NMMA
Healthy subjects
Nephrology

Additional relevant MeSH terms:
Cardiovascular Diseases
Atorvastatin
Nitric Oxide
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on September 18, 2014