Clinical trial NCT00732069: Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis
Official title: Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End Stage Renal Failure on Dialysis
Complication of Hemodialysis
Keywords: hemodialysis
oxidative stress
inflammation
kallikrein-kinin
angiotensin receptor blockade
angiotensin converting enzyme inhibition
RAAS
fibrinolysis
endothelial dysfunction
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-08-11
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility 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

Primary outcomes:
measure: Interleukin 1 Beta
timeFrame: During dialysis after one week of study drug
Secondary outcomes:
measure: F2-Isoprostanes
timeFrame: During dialysis after one week of study drug
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Nancy J Brown, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.