Chronic Kidney DiseaseNCT00356265
Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide
A study testing Procedure: Regional phenylephrine arterial infusion in people with Chronic Kidney Disease and Hypertension, run by University of Michigan at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease, Hypertension
- What is being tested?
- Procedure: Regional phenylephrine arterial infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Nov 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- People with:
- Diabetes
- Lung disease
- Stomach disease
- Liver disease
- Blood vessel disease
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Hospital
Ann Arbor, Michigan, 48109
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Hypertension
- Being tested
- Procedure: Regional phenylephrine arterial infusion
- Keywords
- Blood Pressure Nitric Oxide, L-NMMA, Phenylephrine, Vasoreactivity, Blood Pressure
- Medical subject headings
- Renal Insufficiency, Chronic, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procedure: Regional phenylephrine arterial infusionDrug
| Study group | Role | What they receive |
|---|---|---|
| CKD | Experimental | Not described Receives: Drug: Procedure: Regional phenylephrine arterial infusion |
| Hypertension group | Active comparator | Not described Receives: Drug: Procedure: Regional phenylephrine arterial infusion |
| Normotensive group | Active comparator | Not described Receives: Drug: Procedure: Regional phenylephrine arterial infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
α1-adrenoceptor Vasoreactivity With L-NMMA
Vasoreactivity is defined as Forearm blood flow, dose response curve; ml per minute per log of phenylephrine, or FABF ml/min/logPE;
The x axis is the ml/min value and the y axis is the log Phenylephrine concentration.
Measured: up to 8 hours
α1-adrenoceptor Vasoreactivity With Endogenous ADMA
Measured: up to 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: Futility: Impossible to recruit enough hypertensive participants to match Chronic Kidney Disease (CKD) participants on needed parameters.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All three groups will have the same intervention
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Crystal A. Gadegbeku, University of Michigan
- Investigators
- Crystal A Gadegbeku, MD, Principal investigator, Assistant Professor of Medicine, University of Michigan Health System, Department of Internal Medicine, Division of Nephrology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00356265
- Sponsor's protocol ID
- HUM 00000261
- Other IDs
- 5R33DK071222
- Status last verified
- Dec 2017
- First submitted
- 24 Jul 2006
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide
- ClinicalTrials.gov ID
- NCT00356265
- Acronym / sponsor ID
- HUM 00000261
- Conditions
- Chronic Kidney Disease, Hypertension
- Keywords
- Blood Pressure Nitric Oxide, L-NMMA, Phenylephrine, Vasoreactivity, Blood Pressure
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility: Impossible to recruit enough hypertensive participants to match Chronic Kidney Disease (CKD) participants on needed parameters.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2006 (actual)
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 25 Jul 2006 (estimated)
- Results
- Posted 23 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- All three groups will have the same intervention
| Arm | Type | Receives |
|---|---|---|
| CKD | Experimental | Drug: Procedure: Regional phenylephrine arterial infusion |
| Hypertension group | Active comparator | Drug: Procedure: Regional phenylephrine arterial infusion |
| Normotensive group | Active comparator | Drug: Procedure: Regional phenylephrine arterial infusion |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men and Women-18 to 55 years of age.
- There are three groups of volunteers.
Key exclusion criteria (12 listed)
- Diabetes
- Lung disease
- Stomach disease
- Liver disease
- Blood vessel disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Procedure: Regional phenylephrine arterial infusion | Drug | CKD, Hypertension group, Normotensive group |
Primary outcome
α1-adrenoceptor Vasoreactivity With L-NMMA
Time frame: up to 8 hours
Vasoreactivity is defined as Forearm blood flow, dose response curve; ml per minute per log of phenylephrine, or FABF ml/min/logPE; The x axis is the ml/min value and the y axis is the log Phenylephrine concentration.
α1-adrenoceptor Vasoreactivity With Endogenous ADMA
Time frame: up to 8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Crystal A Gadegbeku, MD principal investigator
Assistant Professor of Medicine, University of Michigan Health System, Department of Internal Medicine, Division of Nephrology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Procedure: Regional phenylephrine arterial infusion in people with Chronic Kidney Disease and Hypertension, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
α1-adrenoceptor Vasoreactivity With L-NMMA (time frame: up to 8 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.