Renal Insufficiency, ChronicPhase 4NCT01663103
Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)
A Phase 4 study testing Rilonacept in people with Renal Insufficiency, Chronic, run by University of Colorado, Denver at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- Rilonacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2012to Dec 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Clinical and Translational Research Center (CTRC) Outpatient Clinic
Aurora, Colorado, 80045
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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
- Being tested
- Rilonacept, Placebo
- Keywords
- Interleukin-1, Endothelium, Vascular, Vascular Stiffness, Oxidative Stress, Inflammation, Endothelial cells
- Medical subject headings
- Renal Insufficiency, Chronic, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RilonaceptDrug
Also called Arcalyst
12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
PlaceboDrug
Also called normal saline
Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
| Study group | Role | What they receive |
|---|---|---|
| Rilonacept | Experimental | 12 weeks of treatment with rilonacept Receives: Drug: Rilonacept |
| Placebo | Placebo comparator | Twelve weeks of treatment with placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months after start of treatment
Secondary outcomes (2)
Change in Aortic Pulse-wave Velocity (aPWV)
Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Measured: 3 months after start of treatment
Change in Contribution of Oxidative Stress to FMD
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.
Measured: 3 months after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristen L Jablonski Nowak, Ph.D., Principal investigator, University of Colorado Denver Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663103
- Sponsor's protocol ID
- 12-0586
- Status last verified
- Jun 2016
- First submitted
- 7 Aug 2012
- Last updated
- 12 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)
- ClinicalTrials.gov ID
- NCT01663103
- Acronym / sponsor ID
- 12-0586
- Conditions
- Renal Insufficiency, Chronic
- Keywords
- Interleukin-1, Endothelium, Vascular, Vascular Stiffness, Oxidative Stress, Inflammation, Endothelial cells
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 13 Aug 2012 (estimated)
- Results
- Posted 12 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rilonacept | Experimental | Drug: Rilonacept12 weeks of treatment with rilonacept |
| Placebo | Placebo comparator | Drug: PlaceboTwelve weeks of treatment with placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (21 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RilonaceptAlso: Arcalyst12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk) | Drug | Rilonacept |
| PlaceboAlso: normal salineTwelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk) | Drug | Placebo |
Primary outcome
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.
2 secondary outcomes
Change in Aortic Pulse-wave Velocity (aPWV)
Time frame: 3 months after start of treatment
Change in Contribution of Oxidative Stress to FMD
Time frame: 3 months after start of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristen L Jablonski Nowak, Ph.D. principal investigator
University of Colorado Denver Anschutz Medical Campus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rilonacept in people with Renal Insufficiency, Chronic, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Flow-mediated Dilation (FMD) (time frame: 3 months after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2016.