Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis
June 22, 2013 updated by: Nancy J. Brown, Vanderbilt University
Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2
Little is known about how some drugs affect inflammation or clotting factors in people receiving hemodialysis.
It is not yet known if these drugs help prevent heart damage as they do in people not undergoing hemodialysis or whether they could increase the risk of heart problems.
The purpose of the study is to measure certain chemicals in the blood and see how those chemicals may change during hemodialysis when certain drugs are given.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
- Cardiovascular disease in the leading cause of death in patients with chronic kidney disease undergoing hemodialysis.
- Traditional risk factors do not adequately predict cardiovascular morbidity and mortality in patients with chronic kidney disease.
- Increased oxidative stress, inflammation and impaired fibrinolysis contribute to cardiovascular risk in chronic kidney disease patients undergoing hemodialysis.
- Activation of the renin-angiotensin-aldosterone system(RAAS) may contribute to oxidative stress and inflammation in individuals with chronic kidney disease
- Activation of the kallikrein-kinin system during hemodialysis may increase fibrinolysis but may also contribute to inflammation in chronic kidney disease
- Despite data from clinical trials demonstrating that ARBs and ACE inhibitors decrease cardiovascular mortality, delay progression to cardiovascular disease and decrease the incidence of diabetes in the general population little is known about the impact of these agents on cardiovascular morbidity and mortality in patients with end- stage renal disease (ESRD) undergoing hemodialysis
- Angiotensin-converting enzyme(ACE) inhibitors and angiotensin receptor blockers (ARB)S differ in their mechanisms of action and their effects on inflammatory biomarkers
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37323
- Vanderbilt University Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age 18 years or older
- On thrice-weekly chronic hemodialysis for at least 6 months
- Clinically stable, adequately dialyzed (single-pool Kt/V> 1.2) thrice weekly, with polysulphone membrane for at least 3 consecutive months prior to study
Exclusion Criteria:
- Body mass index > 35 mg/kg
- History of functional transplant less than 6 months prior to study
- Use of anti-inflammatory medications other than aspirin < 325 mg/d
- History of active connective tissue disease
- History of acute infectious disease within one month prior to study
- AIDS (HIV seropositivity is not an exclusion criteria)
- History of myocardial infarction or cerebrovascular event within 3 months
- Advanced liver disease
- Gastrointestinal dysfunction requiring parental nutrition
- Active malignancy excluding basal cell carcinoma of the skin
- History of ACE inhibitor-associated cough or angioedema
- Ejection fraction less than 40%
- Inability to discontinue ACE inhibitor or ARB
- Predialysis potassium repeatedly higher than 5.5 mmol/L (confirmed on a repeated blood draw)
- Anticipated live donor kidney transplant
- Use of vitamin E >60 IU/d or vitamin C >500 mg/d
- Pregnancy, breast-feeding or child-bearing potential
- History of poor adherence to hemodialysis or medical regimen
- Inability to provide consent
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Placebo, then ramipril, then valsartan
placebo, ramipril, valsartan: Subjects were treated sequentially with placebo, ramipril (5mg/day by mouth), then valsartan (160mg/day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
|
Active Comparator: Placebo, then valsartan, then ramipril
placebo, ramipril, valsartan: Subjects were treated sequentially with placebo, valsartan (160mg/day by mouth), then ramipril (5mg/day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
|
Active Comparator: Ramipril, then placebo, then valsartan
placebo, ramipril, valsartan: Subjects were treated sequentially with ramipril (5mg/day by mouth), then placebo (once a day by mouth), then valsartan (160mg/day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
|
Active Comparator: Valsartan, then placebo, then ramipril
placebo, ramipril, valsartan: Subjects were treated sequentially with valsartan (160mg/day by mouth), then placebo (once a day by mouth), then ramipril (5mg/day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
|
Active Comparator: Ramipril, then valsartan, then placebo
placebo, ramipril, valsartan: Subjects were treated sequentially with ramipril (5mg/day by mouth), then valsartan (160mg/day by mouth), then placebo (once a day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
|
Active Comparator: Valsartan, then ramipril, then placebo
placebo, ramipril, valsartan: Subjects were treated sequentially with then valsartan (160mg/day by mouth), then ramipril (5mg/day by mouth), then placebo (once a day by mouth).
Each drug was given for 7 days after a 3-week washout.
|
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
Patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker before the study underwent washout for 3 weeks.
Subjects were treated with study drug for 7 days and each treatment period was separated by a 3-week washout period.
Ramipril was given at dose of 2.5mg/d for two days, then 5mg/d for 5 days.
Valsartan was given at 80mg/d for 2 days followed by 160mg/d for 5 days.
On the seventh day of each treatment blood samples were collected prior two, during and two hours after dialysis
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Interleukin 1 Beta
Time Frame: During dialysis after one week of study drug
|
Mean difference in interleukin 1 beta concentration during treatment with ramipril versus treatment with placebo
|
During dialysis after one week of study drug
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
F2-Isoprostanes
Time Frame: During dialysis after one week of study drug
|
Mean difference in F2-isoprostanes during dialysis between treatment with ramipril or valsartan and placebo
|
During dialysis after one week of study drug
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ. Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis. J Am Soc Nephrol. 2012 Feb;23(2):334-42. doi: 10.1681/ASN.2011030287. Epub 2011 Dec 8.
- Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study. BMC Nephrol. 2015 Oct 22;16:167. doi: 10.1186/s12882-015-0162-x.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2008
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
December 1, 2011
Study Registration Dates
First Submitted
August 6, 2008
First Submitted That Met QC Criteria
August 6, 2008
First Posted (Estimate)
August 11, 2008
Study Record Updates
Last Update Posted (Estimate)
July 2, 2013
Last Update Submitted That Met QC Criteria
June 22, 2013
Last Verified
June 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Renal Insufficiency, Chronic
- Kidney Failure, Chronic
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Angiotensin-Converting Enzyme Inhibitors
- Valsartan
- Ramipril
Other Study ID Numbers
- Fibrinolysis in Dialysis
- R01HL065193-08A2 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.