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

August 2, 2016 updated by: University of Colorado, Denver
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Clinical and Translational Research Center (CTRC) Outpatient Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Rilonacept
12 weeks of treatment with rilonacept
Drug: Rilonacept
12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
Other Names:
  • Arcalyst
PLACEBO_COMPARATOR: Placebo
Twelve weeks of treatment with placebo
Drug: Placebo
Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
Other Names:
  • normal saline

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Flow-mediated Dilation (FMD)
Time Frame: 3 months after start of treatment
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Aortic Pulse-wave Velocity (aPWV)
Time Frame: 3 months after start of treatment
Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.
3 months after start of treatment
Change in Contribution of Oxidative Stress to FMD
Time Frame: 3 months after start of treatment
FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.
3 months after start of treatment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in High-sensitivity C-reactive Protein (hsCRP)
Time Frame: 3 months after start of treatment
Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.
3 months after start of treatment
Change in Vascular Endothelial NADPH Oxidase Expression
Time Frame: 3 months after start of treatment
Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.
3 months after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Colorado, Denver

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kristen L Jablonski Nowak, Ph.D., University of Colorado Denver Anschutz Medical Campus

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 7, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 13, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12-0586

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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