Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

Phase 2

Completed

Conditions: End Stage Renal Failure on Dialysis
Complication of Hemodialysis

Interventions: Drug: Placebo
Drug: Ramipril
Drug: Valsartan

Registration Number: NCT00732069

Lead Sponsor: Vanderbilt University

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo, then ramipril, then valsartan	Placebo	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.
Placebo, then ramipril, then valsartan	Ramipril	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.
Placebo, then valsartan, then ramipril	Placebo	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.
Ramipril, then placebo, then valsartan	Placebo	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.
Valsartan, then placebo, then ramipril	Placebo	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.
Ramipril, then valsartan, then placebo	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.
Valsartan, then ramipril, then placebo	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.
Placebo, then ramipril, then valsartan	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.
Ramipril, then placebo, then valsartan	Ramipril	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.
Placebo, then valsartan, then ramipril	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.
Placebo, then valsartan, then ramipril	Valsartan	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.
Ramipril, then placebo, then valsartan	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.
Valsartan, then placebo, then ramipril	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.
Valsartan, then placebo, then ramipril	Valsartan	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.
Ramipril, then valsartan, then placebo	Valsartan	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.
Ramipril, then valsartan, then placebo	Ramipril	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.
Valsartan, then ramipril, then placebo	Ramipril	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.
Valsartan, then ramipril, then placebo	Valsartan	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.

Primary Outcome Measures

Name	Time	Method
Interleukin 1 Beta	During dialysis after one week of study drug	Mean difference in interleukin 1 beta concentration during treatment with ramipril versus treatment with placebo

Secondary Outcome Measures

Name	Time	Method
F2-Isoprostanes	During dialysis after one week of study drug	Mean difference in F2-isoprostanes during dialysis between treatment with ramipril or valsartan and placebo