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

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT00356265

First Posted: July 25, 2006

Last Update Posted: September 1, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Information provided by (Responsible Party):

Crystal A. Gadegbeku, University of Michigan

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 Intervention Model: Parallel Assignment Intervention Model Description: All three groups will have the same intervention Masking: None (Open Label) Primary Purpose: Other
Official Title:	Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide

Resource links provided by NLM:

MedlinePlus related topics: Kidney Diseases

Drug Information available for: Phenylephrine Nitric oxide

U.S. FDA Resources

Further study details as provided by Crystal A. Gadegbeku, University of Michigan:

Primary Outcome Measures:

α1-adrenoceptor vasoreactivity with L-NMMA [ Time Frame: up to 8 hours ]
α1-adrenoceptor vasoreactivity with endogenous ADMA [ Time Frame: up to 8 hours ]


Enrollment:	19
Actual Study Start Date:	July 2006
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CKD	Drug: Procedure: Regional phenylephrine arterial infusion
Active Comparator: Hypertension group	Drug: Procedure: Regional phenylephrine arterial infusion
Active Comparator: Normotensive group	Drug: Procedure: Regional phenylephrine arterial infusion

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:

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.

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

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00356265

Locations


United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

Additional Information:

Principle Investigator research information This link exits the ClinicalTrials.gov site


Responsible Party:	Crystal A. Gadegbeku, Associate Professor of Medicine, University of Michigan
ClinicalTrials.gov Identifier:	NCT00356265 History of Changes
Other Study ID Numbers:	HUM 00000261 5R33DK071222 ( U.S. NIH Grant/Contract )
First Submitted:	July 24, 2006
First Posted:	July 25, 2006
Last Update Posted:	September 1, 2017
Last Verified:	August 2017

Keywords provided by Crystal A. Gadegbeku, University of Michigan:


Blood Pressure Nitric Oxide L-NMMA Phenylephrine Vasoreactivity Blood Pressure

Additional relevant MeSH terms:


Kidney Diseases Renal Insufficiency, Chronic Urologic Diseases Renal Insufficiency Nitric Oxide Phenylephrine Oxymetazoline Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Free Radical Scavengers Antioxidants	Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Endothelium-Dependent Relaxing Factors Vasodilator Agents Gasotransmitters Protective Agents Cardiotonic Agents Mydriatics Sympathomimetics Vasoconstrictor Agents Nasal Decongestants Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents

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