Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2006 by University of Michigan.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00356265
First received: July 24, 2006
Last updated: December 1, 2006
Last verified: December 2006
  Purpose

The purpose of this study is to learn more about why most patients with early stages of kidney disease have high blood pressure.

We know the body produces natural substances that cause blood vessels to open wider to carry more blood when needed. An example is during exercise. Other natural substances cause blood vessels to get smaller and slow down blood flow when needed. An example is when people are cold. The balance between these substances is important. People with kidney disease and high blood pressure do not have the normal balance of these substances.

This study will include 3 groups of people, people with normal blood pressure, people with high blood pressure and people with kidney disease.

  • Subjects will have a screening physical examination, including an ECG and laboratory tests
  • Subjects with high blood pressure may not take their regular blood pressure medication for 3 weeks prior to the inpatient GCRC study
  • Subjects will be given intra-arterial medications that will cause changes in the blood vessels during the in-patient study.

The study will then compare the responses of the three groups. A GFR test will be done to confirm the renal function of the group with chronic kidney disease.

These studies will provide insight into the mechanisms of the pathogenesis of enhanced α1 vasoreactivity in subjects with progressive renal disease. This will lay the groundwork for new strategies in the treatment and prevention of vascular disease among the rapidly growing group of individuals with CKD.


Condition Intervention
Chronic Kidney Disease
Hypertension
Drug: Procedure: Regional phenylephrine arterial infusion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Educational/Counseling/Training
Official Title: Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Determine if α1-adrenoceptor vasoreactivity is enhanced less by inhibition of endothelial NO
  • Determine whether α1-adrenoceptor vasoreactivity correlates with plasma levels of the endogenous NO inhibitor, asymmetrical dimethylarginine.

Estimated Enrollment: 39
Study Start Date: July 2006
Estimated Study Completion Date: June 2008
Detailed Description:

Enhanced adrenergic vascular reactivity may significantly contribute to hypertension and the excessive cardiovascular disease burden in patients with chronic kidney disease (CKD). Nitric oxide (NO), a modulator of neurovascular function, may be linked to adrenergic vascular responsiveness. The central HYPOTHESIS is that the reduction in endothelial nitric oxide (NO) bioavailability contributes to the enhancement of α1-adrenoceptor vasomotor function in patients with CKD.

Specific Aims: In patients with mild to moderate CKD, compared to matched hypertensive and normotensive controls without CKD:

  1. Determine if α1-adrenoceptor vasoreactivity is enhanced less by inhibition of endothelial NO
  2. Determine whether α1-adrenoceptor vasoreactivity correlates with plasma levels of the endogenous NO inhibitor, asymmetrical dimethylarginine.

Methods: CKD will be confirmed by I125-iothalamate glomerular filtration rate. Regional α1-adrenoceptor vasoreactivity (sensitivity [EC50], reactivity [slope]) will be assessed by venous plethsymography using a graded intra-arterial infusion of the α1-adrenoceptor agonist, phenylephrine. Comparisons of vasoreactivity at baseline and during infusions of L-NMMA will be made between hypertensive non-diabetic subjects with glomerular filtrations rates between 30-70 ml/min age-, gender-, ethnicity- and % body fat-matched hypertensive and normotensive subjects with normal kidney function. In addition, plasma levels of the endogenous NO inhibitor, asymmetric dimethylarginine will be measured in the hypertensive subjects with and without CKD and compared to vasoreactivity.

Significance. These studies will provide insight into the mechanisms of the pathogenesis of enhanced α1 vasoreactivity in subjects with progressive renal disease.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and Women-18 to 55 years of age.
  • There are three groups of volunteers.

    • Group A. People who are hypertensive with kidney disease. When not taking blood pressure medicines, blood pressure must have a systolic between 140-170 mmHg. Diastolic must be between 90-109 mmHg.Kidney function should be around half of normal. Urine protein must be no more than 1 gram in a 24-hour urine time period.
    • Group B. People who are hypertensive without kidney disease. Blood pressure must have a systolic between 140-170 mmHg. Diastolic must be between 90-109 mmHg. Kidney function should be normal. Normal amounts of protein in their urine.
    • Group C. People who are normotensive. Blood pressure must have a systolic below 131/mmHg. Diastolic must be below 81 mmHg. Kidney function should be normal. No more than normal amounts of protein in their urine.

Exclusion Criteria:

People with:

  • Diabetes
  • Lung disease
  • Stomach disease
  • Liver disease
  • Blood vessel disease
  • Heart disease
  • Hereditary blood disorders
  • Hematocrit (amount of red blood cells) less than 30%
  • Current tobacco use
  • Kidney disease who require dialysis
  • Women who are pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00356265

Contacts
Contact: Kathryn M Lindblad, RN,MS, CCRC 734-764-5187 Lindblad@umich.edu

Locations
United States, Michigan
University of Michigan Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Crystal A Gadegbeku, MD         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Crystal A Gadegbeku, MD Assistant Professor of Medicine, University of Michigan Health System, Department of Internal Medicine, Division of Nephrology
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00356265     History of Changes
Other Study ID Numbers: HUM 00000261, 5R33DK071222-02
Study First Received: July 24, 2006
Last Updated: December 1, 2006
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Blood Pressure Nitric Oxide
L-NMMA
Phenylephrine
Vasoreactivity
Blood Pressure

Additional relevant MeSH terms:
Hypertension
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Nitric Oxide
Phenylephrine
Oxymetazoline
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on April 17, 2014