Inflammation in Chronic Kidney Disease and Cardiovascular Disease - The Role of Genetics and Interleukin-1 Receptor Antagonist (IL-1ra)

This study is currently recruiting participants.
Verified January 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00897715
First received: May 8, 2009
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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 CV 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 Intervention
Chronic Kidney Disease
Cardiovascular Disease
Drug: Rilonacept
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inflammation in CKD and CVD - The Role of Genetics and IL-1ra

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • High Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation


Secondary Outcome Measures:
  • Interleukin-6 (IL-6) [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 54
Study Start Date: January 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Interleukin-1 receptor antagonist
active drug
Drug: Rilonacept
160 mg administered subcutaneously once a week for 24 weeks
Other Name: Arcalyst
Placebo Comparator: Placebo
matching placebo
Drug: Placebo
160 mg administered subcutaneously once a week for 24 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older;
  • eGFR between 15-60 mL/min/1.73m2;
  • Must be on stable regimens of medications that can affect inflammatory axis (ASA, ACE inhibitors, ARBs, TZDs, statins);
  • Willing and able to comply with clinic visits and study-related procedures;
  • Provide signed informed consent.

Exclusion Criteria:

  • Recent infection or hospitalization (within one month);
  • History of active or chronic hepatitis B, history of active or chronic hepatitis C, human immunodeficiency virus (HIV), history of tuberculosis (patient must be PPD negative);
  • Patients taking TNF inhibitors, TNF blocker, IL-6 blockers or IL-1 blocking drugs;
  • Patients on steroids or receiving any other immunosuppressive agent or anti-inflammatory drug (aspirin up to 100 mg a day is allowed) one month prior;
  • Have clinically significant chronic lymphopenia (low white blood cell count);
  • History of malignancy in the prior 5 years. Any history of melanoma or lymphoma;
  • Life expectancy less than six months;
  • Intolerance to the study medication;
  • The use of any other investigational drug 30 days prior to enrollment or within five half-lives of the medication used;
  • Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose;
  • Currently receiving parenteral iron or scheduled to receive parenteral iron during the study;
  • Uncontrolled diabetes mellitus (HbA1c > 10);
  • hsCRP <1mg/L or >30 mg/L
  • Pregnant or breast-feeding women;
  • Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).

    • Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00897715

Contacts
Contact: Cindy A Booker (615) 343-5828 cindy.a.booker@vanderbilt.edu

Locations
United States, Tennessee
VA Medical Center Recruiting
Nashville, Tennessee, United States, 37212-2637
Contact: Cindy A Booker    615-343-5828    cindy.a.booker@vanderbilt.edu   
Principal Investigator: Adriana M Hung, MD MPH         
Vanderbilt University Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Cindy A Booker, LPN    615-343-5828    cindy.a.booker@vanderbilt.edu   
Sponsors and Collaborators
Investigators
Principal Investigator: Adriana M Hung, MD MPH Department of Veterans Affairs
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00897715     History of Changes
Other Study ID Numbers: CDA-2-031-09S
Study First Received: May 8, 2009
Last Updated: January 28, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
CKD
inflammation
CVD

Additional relevant MeSH terms:
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
Inflammation
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Pathologic Processes
Renal Insufficiency
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014