Inflammation in Chronic Kidney Disease and Cardiovascular Disease - The Role of Genetics and Interleukin-1 Receptor Antagonist (IL-1ra)
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|ClinicalTrials.gov Identifier: NCT00897715|
Recruitment Status : Completed
First Posted : May 12, 2009
Results First Posted : March 17, 2016
Last Update Posted : January 30, 2018
There has been an exponential growth in the number of people with Chronic Kidney Disease (CKD) needing dialysis or transplantation, increasing from 209,000 in 1991 to 472,000 in 2004. This is highly concerning due to both the human cost and the burden that it represents to the health care system. Recent comparison of the NHANES surveys showed that CKD prevalence increased from 10% in 1988-1994 to 13% in 1999-2004. Patients with CKD are more likely to die from premature cardiovascular death than to reach ESRD. In those that reach ESRD, cardiovascular disease (CVD) accounts for over half of the deaths in dialysis. The prevalence of CKD for the VA population is 20%, and 31.6% for diabetics, higher than in the general population. These observations emphasize the need of risk stratification, early detection, and prevention efforts with respect to CKD progression and the CVD burden that afflicts CKD through targeted interventions in high-risk groups (personalized medicine).
CKD is multifactorial, however familial aggregation of end-stage renal disease (ESRD) and CKD have been reported for all types of nephropathy underscoring "kidney disease genetic susceptibility ". Genetic predisposition to ESRD is stronger in African Africans. African Americans with a first-degree relative with ESRD have a 9-fold increase risk of ESRD vs. a 3-5 fold increase in whites.
Studies consistently show that CKD is an inflammatory process and that biomarkers of inflammation increase since early stages of CKD. CVD is also an inflammatory process, and genes that affect inflammation are associated with higher risk of CVD. Since inflammation is a common denominator of both disease processes (CKD and CVD), it is likely that genes that govern inflammation may be involved in both, the predisposition to CKD and the burden of CVD attributable to CKD. Additionally if inflammation plays a central role in the burden of CVD in CKD than drugs that modulate inflammation should impact both: CKD progression and non-traditional CV risk factors and CVD.
The overall goal of this proposal is to study genetic predisposition to CKD, and CVD risk in CKD through inflammatory pathways, and the effect that a potent anti-inflammatory intervention like interleukin 1 receptor antagonist (IL-1ra), will have in inflame patients with CKD stages 3&4. Specific Aims: 1) To determine if specific polymorphism/haplotypes, genotype combinations and gene-environmental interactions that can affect inflammation, available from the Third National Health and Nutrition Examination Survey (DNA data set), specifically in the CRP,IL-1, IL-10 and TNF- genes, are associated with CKD. 2) To determine if the specific polymorphisms and haplotypes studied in Aim 1 are associated with faster CKD progression and CV outcomes in a longitudinal cohort from the African American Study of Kidney Disease. 3)To determine if a targeted anti-inflammatory intervention, an IL-1 receptor antagonist, will modulate systemic inflammation, endothelial function, oxidative stress and urinary cytokines, the proposed surrogate markers of CVD and CKD progression in inflame patients with CKD stages 3&4.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Kidney Disease Cardiovascular Disease||Drug: Rilonacept Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Inflammation in CKD and CVD - The Role of Genetics and IL-1ra|
|Actual Study Start Date :||January 1, 2013|
|Actual Primary Completion Date :||February 25, 2015|
|Actual Study Completion Date :||May 8, 2015|
Active Comparator: Interleukin-1 receptor antagonist
160 mg of rilonacept administered subcutaneously once a week for 12 weeks
Other Name: Arcalyst
Placebo Comparator: Placebo
160 mg of placebo administered subcutaneously once a week for 12 weeks
- Change in the Concentration of High Sensitivity C-Reactive Protein (hsCRP) From Baseline to 12 Weeks [ Time Frame: baseline and 12 weeks ]hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation
- Change in Concentration of Interleukin-6 (IL-6) From Baseline to 12 Weeks [ Time Frame: baseline and 12 weeks ]IL-6 is a sensitive laboratory assay for serum levels of Interleukin-6, which is a pro-inflammatory cytokine that is used to evaluate the inflammatory response
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00897715
|United States, Tennessee|
|Tennessee Valley Healthcare System Nashville Campus, Nashville, TN|
|Nashville, Tennessee, United States, 37212-2637|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Adriana M Hung, MD MPH||Tennessee Valley Healthcare System Nashville Campus, Nashville, TN|