Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

End Stage Renal Failure on Dialysis Clinical Trial

Official title:

Genes, Fibrinolysis and Endothelial Dysfunction- Dialysis Aim 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00732069
• Other study ID #: Fibrinolysis in Dialysis
• Secondary ID: R01HL065193-08A2
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2008
• Last updated: June 22, 2013
• Start date: August 2008
• Est. completion date: December 2011

Study information

• Verified date: June 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• 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) 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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Complication of Hemodialysis
• End Stage Renal Failure on Dialysis
• Kidney Failure, Chronic

Intervention

Drug:
• Placebo
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
• Ramipril
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
• Valsartan
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

Locations

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

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interleukin 1 Beta	Mean difference in interleukin 1 beta concentration during treatment with ramipril versus treatment with placebo	During dialysis after one week of study drug	No
Secondary	F2-Isoprostanes	Mean difference in F2-isoprostanes during dialysis between treatment with ramipril or valsartan and placebo	During dialysis after one week of study drug	No