Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis - Full Text View

Sponsors and Collaborators:	Vanderbilt University National Institutes of Health (NIH)
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00732069

Purpose

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.

Condition	Intervention	Phase
Hemodialysis Renal Dialysis	Drug: ramipril Drug: valsartan Drug: Placebo	Phase II

MedlinePlus related topics: Dialysis Kidney Failure

Drug Information available for: Ramipril Valsartan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Crossover Assignment, Double Blind (Subject, Investigator, Outcomes Assessor), Health Services Research, Pharmacokinetics Study, Randomized
Official Title:	Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

To compare the effect of ACE inhibition or AT1 receptor blockade versus placebo on the fibrinolytic, oxidative stress and inflammatory response to hemodialysis [ Time Frame: end of each study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To compare the effect of ACE inhibition versus AT1 receptor blockade on the fibrinolytic, oxidative stress and inflammatory response to hemodialysis [ Time Frame: end of each study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	18
Study Start Date:	August 2008
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator After a three week washout period, the subject will be undertake 3 study periods with one of three treatments, placebo, ramipril or valsartan	Drug: ramipril After a washout period, subject will undertake 3 study periods with one of the three treatments: Ramipril initiated at 2.5 mg/d for 2 days followed by 5 mg for a total of nine days
2: Active Comparator After a three week washout period, each subject will be randomized to receive one of the three treatments, placebo, ramipril or valsartan	Drug: valsartan After a three week washout period, each subject will undertake 3 study periods with one of three treatment: Valsartan initiated at 80 mg/d for 2 days followed by 160 mg/d for a total of 9 days
3: Placebo Comparator After a three week washout period, each subject will undertake 3 study periods with one of the three treatments, placebo, ramipril or valsartan	Drug: Placebo After a three week washout period, subject will undertake 3 study periods with one of three treatments: Placebo (inactive pill) for nine days.

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 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
ACE inhibitors and ARBS differ in their mechanisms of action and their effects on inflammatory biomarkers

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732069

Contacts

Contact: Delia M Woods, BSN

615-322-3371

delia.woods@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37323
Contact: Delia M Woods, BSN 615-322-3371 delia.woods@vanderbilt.edu
Principal Investigator: Nancy J Brown, MD
Sub-Investigator: Josh Billings, MD

Sponsors and Collaborators

Vanderbilt University

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Nancy J Brown, MD

Vanderbilt University

More Information

No publications provided

Responsible Party:	Vanderbilt University Medical Center ( Nancy J. Brown, MD )
Study ID Numbers:	Fibrinolysis in Dialysis, R01 HL065193-08A2
Study First Received:	August 6, 2008
Last Updated:	February 18, 2009
ClinicalTrials.gov Identifier:	NCT00732069 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

angiotensin converting enzyme inhibition
angiotensin receptor blockade
endothelial dysfunction
fibrinolysis
hemodialysis

inflammation
kallikrein-kinin
oxidative stress
RAAS

Study placed in the following topic categories:

Kallikreins
Angiotensin-Converting Enzyme Inhibitors
Stress
Cardiovascular Agents
Antihypertensive Agents

Ramipril
Valsartan
Protease Inhibitors
Inflammation

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Cardiovascular Agents

Antihypertensive Agents
Pharmacologic Actions
Valsartan
Ramipril
Protease Inhibitors

ClinicalTrials.gov processed this record on March 16, 2009