Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)
Condition: Renal Insufficiency, Chronic
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
Intervention: Rilonacept; Placebo
Intervention description: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk); Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
Intervention MeSH terms: Rilonacept
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Interleukin-1; Endothelium, Vascular; Vascular Stiffness; Oxidative Stress; Inflammation; Endothelial cells

Summary:

      Risk of cardiovascular diseases (CVD) is significantly elevated in patients with chronic
      kidney disease (CKD); however, this increased risk is only partially explained by traditional
      cardiovascular risk factors. Patients with CKD exhibit chronic inflammation, a key mechanism
      contributing to vascular dysfunction (i.e., large elastic artery stiffening and endothelial
      dysfunction). Inhibiting inflammation improves vascular dysfunction in other populations
      characterized by chronic inflammation. However, it is currently unknown if reducing
      inflammation with an interleukin-1 (IL-1) blocker enhances vascular function in CKD patients.
      Aim 1 will assess the efficacy of IL-1 blocking with rilonacept for treating vascular
      dysfunction in patients with stage III or IV CKD (estimated glomerular filtration rate 15-60
      mL/min/1.73 m2). Aim 2 will determine if blocking IL-1 with rilonacept also reduces
      inflammation and oxidative stress. These studies could shift clinical practice guidelines by
      establishing a novel therapy for reducing CVD risk in CKD patients not requiring chronic
      hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-80 years

          -  CKD stage III or IV (eGFR with the 4-variable Modified Diet Renal Disease (MDRD)
             prediction equation: 15-60 mL/min/1.73m2; stable renal function in the past 3 months)

          -  An elevated high sensitivity C-reactive protein (hs-CRP) of > 2.0 mg/L and <30 mg/L on
             at least 2 consecutive weekly determinations

          -  Urine protein excretion < 5.0 g/24h estimated by a spot urine protein/creatinine ratio

          -  Ability to provide informed consent

        Exclusion Criteria:

          -  Patients with advanced CKD requiring chronic dialysis

          -  Active infection (chronic or acute (within 3 months) or antibiotic therapy (w/in 1
             mo); history of recurrent infection

          -  Significant co-morbid conditions that lead the investigator to conclude that life
             expectancy is less than 1 year

          -  Expected to undergo living related transplant in next 6 months

          -  History of severe congestive heart failure (i.e., EF < 35%)

          -  Hospitalization in the past month

          -  Severe arthritis, lupus, inflammatory bowel disease, asthma or other disease(s) or
             medical condition(s) that, in the opinion of the investigator, could interfere with
             hsCRP or immune function

          -  Immunosuppressant agents such as cyclosporine, tacrolimus, azathioprine, etanercept,
             infliximab, adalimumab, anakinra or long-term oral glucocorticoids taken in past 12
             months

          -  Known malignancy

          -  HIV, active, chronic hepatitis B as evidenced by HBsAg positive and HBsAb negative, or
             hepatitis C positive

          -  Woman who are pregnant, nursing or planning to become pregnant

          -  Body mass index (BMI) >40 kg/m2

          -  Warfarin use (or other cytochrome P (CYP)450 substrates with a narrow therapeutic
             index) [ok if do not participate in endothelial cell collection]

          -  Taking medication(s) that interact with agents administered during experimental
             sessions (e.g., sildenafil interacts with nitroglycerin)

          -  Currently receiving or planning to receive live or inactivated vaccines

          -  Alcohol dependence or abuse

          -  Subjects at risk for tuberculosis (TB). Specifically, subjects with:

          -  Current clinical, radiographic or laboratory evidence of active TB at screening or
             latent TB that has not been previously treated

          -  A history of active TB within the last 3 years even if it was treated.

          -  A history of active TB greater than 3 years ago unless there is documentation that the
             prior anti-TB treatment was appropriate in duration and type.

          -  Therapy for latent TB which has not been completed as per local guidelines.