Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00878969
Other study ID # Fibrinolysis in Dialysis Aim 3
Secondary ID R01HL065193-08A2
Status Terminated
Phase Phase 3
First received April 8, 2009
Last updated January 18, 2016
Start date January 2010
Est. completion date June 2015

Study information

Verified date January 2016
Source Vanderbilt University
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

The purpose of the study is to see how two classes of blood pressure medications,angiotensin-converting enzyme inhibitors (Ace inhibitors) and angiotensin receptor blockers (ARBs), differ in their long term effects on certain chemicals in the body and on the carotid arteries.


Description:

More than 400,000 individuals with chronic kidney disease undergo hemodialysis each year in the United States. Atherosclerotic cardiovascular disease is the leading cause of mortality in these patients. Conventional risk factors for coronary artery disease (CAD) do not adequately explain this increased mortality, whereas biomarker of oxidative stress and inflammation correlate with clinical outcomes. Even with the use of biocompatible membranes, hemodialysis induces a systemic inflammatory reaction characterized by complement activation, leukocyte activation and the generation of reactive oxygen species and cytokines. Oxidative stress and inflammation promote endothelial dysfunction, a predictor of atherosclerotic cardiovascular events.

The purpose of the study is to test the hypothesis that angiotensin-converting enzyme inhibition and angiotensin receptor blockade differ in their long term effects on biomarkers of fibrinolysis, oxidative stress,inflammation and on carotid intima-media thickness (IMT), a predictor of cardiovascular events, in patients with chronic kidney disease undergoing maintenance hemodialysis.

Endogenous Bradykinin (BK) contributes to the hypotensive and pro-fibrinolytic effects of ACE inhibitors. It has been determined that endogenous BK contributes to the vasodilator effects of acute and chronic ACE inhibition. Studies have found that BK stimulates vascular tissue plasminogen activator (t-PA) release through a BK B2 receptor-dependent, nitric oxide (NO) and cyclooxygenase-independent pathway. Hemodialysis patients demonstrates endothelial dysfunction. Data suggests that t-PA release may be attenuated during stimulation of the endogenous kallikrein-kinin system by hemodialysis.

Intra-arterial infusion of BK increases vascular release of F2- isoprostanes, markers of oxidative stress, BK infusions also increase net release of the inflammatory cytokine interleukin-6 (IL-6). Preliminary data raise the possibility that activation of the endogenous kallikrein-kinin system during dialysis could promote inflammation in individuals with chronic kidney disease who are treated with an ACE inhibitor.

Cardiopulmonary bypass activates the endogenous kallikrein-kinin system and causes a systemic inflammatory response. Like hemodialysis, cardiopulmonary bypass activates the endogenous kallikrein-kinin system, increasing BK concentrations. In smokers, who like hemodialysis patients exhibit endothelial dysfunction, the t-PA response to BK was attenuated during cardiopulmonary bypass.

ACE inhibition enhances fibrinolysis and decreases inflammation following cardiopulmonary bypass. The short-term effect of both ACE inhibition and angiotensin II type 1 (AT1) receptors on markers of fibrinolysis and inflammation during dialysis are currently being studied.

Circulating BK concentrations are increased during hemodialysis in individuals treated with an ACE inhibitors compared to those treated with an AT1 receptor blocker.

Bradykinin receptor blockade and the fibrinolytic and inflammatory response to hemodialysis. It is hypothesized that subjects with CAD, the t-PA response to hemodialysis will be blunted compared to that measured in subjects without evidence of CAD, whereas the inflammatory response wil be similar or enhanced.


Recruitment information / eligibility

Status Terminated
Enrollment 78
Est. completion date June 2015
Est. primary completion date June 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years and older
Eligibility 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 or Urea Reduction Ratio (URR) > 65%] thrice weekly, with polysulphone membrane for at least 3 consecutive months prior to study

Exclusion Criteria:

- History of functional transplant less than 6 months prior to study

- Use of immunosuppressive drugs within 1 month prior to study

- 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 (intolerable) or angioedema

- Ejection fraction less than 30%

- Inability to discontinue ACE inhibitor or ARB

- Predialysis potassium repeatedly higher than 6.0 mmol/L (confirmed on a repeated blood draw)

- Anticipated live donor kidney transplant

- Pregnancy or breast-feeding

- History of poor adherence to hemodialysis or medical regimen

- Inability to provide consent

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Health Services Research


Related Conditions & MeSH terms


Intervention

Drug:
valsartan (ARB)

ramipril (ACE inhibitor)

Placebo


Locations

Country Name City State
United States Vanderbilt University Medical Center Nashville Tennessee

Sponsors (3)

Lead Sponsor Collaborator
Vanderbilt University National Heart, Lung, and Blood Institute (NHLBI), University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Interleukin-6 (IL-6) IL-6 is a sensitive laboratory assay for serum levels of interleukin-6, which is a pro-inflammatory cytokine used to evaluate the inflammatory response. baseline and 18 months No
See also
  Status Clinical Trial Phase
Completed NCT03255187 - Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution N/A
Completed NCT04136821 - The Long-term Effects of Oceanix™ on Resistance Training Adaptations N/A
Recruiting NCT03790345 - Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics Phase 2/Phase 3
Completed NCT03358524 - Effects of Vitamin E Supplementation on Free Radicals and Fat Level of Obese Adolescence in Jakarta, Indonesia Phase 4
Recruiting NCT05327348 - Effectiveness of IV Vitamin C in Reducing Oxidative Stress Associated With Free Flap Surgery Phase 3
Completed NCT03288623 - The Effects of Dark Chocolate Implementation in Elite Athletes N/A
Completed NCT04419025 - Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease Phase 2
Completed NCT04597983 - Effect of 8-week Intake of 2S-hesperidin on Performance, Body Composition and Biochemicals Markers in Amateur Cyclists N/A
Not yet recruiting NCT06159543 - The Effects of Fresh Mango Consumption on Cardiometabolic Outcomes in Free-living Individuals With Prediabetes N/A
Enrolling by invitation NCT03030456 - Whole Body Vibrations on Functional Capacity, Muscular Strength, and Biochemical Profile in Elders N/A
Completed NCT02256254 - SIMOX - Induction of Oxidative Stress Phase 2
Not yet recruiting NCT02202239 - Effect of Induction and Maintenance of Anesthesia With Etomidate on Hemodynamics and Oxidative Stress in Diabetic Patients Phase 4
Recruiting NCT02048592 - Impact of Immunonutrition on the Patients With Cystic Fibrosis Phase 4
Completed NCT01942460 - Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients Phase 4
Completed NCT02463318 - The Effect of Melatonin on Gene Expression and Activity of the Sirt1 and Its Target Genes Catalase and MnSOD in Multiple Sclerosis Patients and Healthy Subjects N/A
Completed NCT02177383 - Action of Essential Fatty Acids on the Expression of Antioxidant Genes and Athletic Performance N/A
Completed NCT01990391 - Brazil Nut Consumption in Microvascular Endothelial Function, Oxidative Stress and Metabolic Abnormalities N/A
Completed NCT00845130 - Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes N/A
Completed NCT00607893 - Efficacy of Continuous Positive Airway Pressure in Reducing Oxidative Stress in Individuals With Sleep Apnea N/A
Active, not recruiting NCT00247507 - The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients Phase 4