Study of Inflammation and Oxidative Stress in Persons Undergoing Dialysis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by Vanderbilt University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00732069
First received: August 6, 2008
Last updated: October 21, 2010
Last verified: October 2010
  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
Renal Dialysis
Hemodialysis
Drug: ramipril
Drug: valsartan
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


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: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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
Other Name: Altace
Active Comparator: 2
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
Other Name: Diovan
Placebo Comparator: 3
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.
Other Name: Placebo

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

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37323
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Nancy J Brown, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Nancy J. Brown, MD, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00732069     History of Changes
Other Study ID Numbers: Fibrinolysis in Dialysis, R01 HL065193-08A2
Study First Received: August 6, 2008
Last Updated: October 21, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
hemodialysis
oxidative stress
inflammation
kallikrein-kinin
angiotensin receptor blockade
angiotensin converting enzyme inhibition
RAAS
fibrinolysis
endothelial dysfunction

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Ramipril
Valsartan
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 22, 2013