Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)

NCT01663103 | Completed Phase 4 Results DMC

• 1 other identifier: 12-0586
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Renal Insufficiency, Chronic

Keywords

Interleukin-1; Endothelium, Vascular; Vascular Stiffness; Oxidative Stress; Inflammation; Endothelial cells

Outcome Measures

Primary Outcomes (1)

• Change in Flow-mediated Dilation (FMD)

  Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.

  3 months after start of treatment

Secondary Outcomes (2)

• Change in Aortic Pulse-wave Velocity (aPWV)

  3 months after start of treatment

• Change in Contribution of Oxidative Stress to FMD

  3 months after start of treatment

Other Outcomes (2)

• Change in High-sensitivity C-reactive Protein (hsCRP)

  3 months after start of treatment

• Change in Vascular Endothelial NADPH Oxidase Expression

  3 months after start of treatment

Study Arms (2)

Rilonacept

EXPERIMENTAL

12 weeks of treatment with rilonacept

Drug: Rilonacept

Placebo

PLACEBO COMPARATOR

Twelve weeks of treatment with placebo

Drug: Placebo

Interventions

Rilonacept DRUG

12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)

Also known as: Arcalyst

Rilonacept

Placebo DRUG

Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)

Also known as: normal saline

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (2)

University of Colorado Clinical and Translational Research Center (CTRC) Outpatient Clinic

Aurora, Colorado, 80045, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Inflammation

Interventions

rilonacept; Saline Solution

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Kristen Nowak
• Organization: University of Colorado Anschutz Medical Campus

Kristen.Nowak@ucdenver.edu

303-724-4842

Study Officials

• Kristen L Jablonski Nowak, Ph.D.

  University of Colorado Denver Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 13, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 12, 2016
• Results First Posted: September 12, 2016

Record last verified: 2016-06

Locations

US (2)