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

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ClinicalTrials.gov Identifier: NCT01663103
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : September 12, 2016
Last Update Posted : September 12, 2016
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Renal Insufficiency, Chronic
Interventions Drug: Rilonacept
Drug: Placebo
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rilonacept Placebo
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12 weeks of treatment with rilonacept

Rilonacept: 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

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

Period Title: Overall Study
Started 21 21
Completed 18 19
Not Completed 3 2
Reason Not Completed
Withdrawal by Subject             1             2
Adverse Event             1             0
dog bite             1             0
Arm/Group Title Rilonacept Placebo Total
Hide Arm/Group Description

12 weeks of treatment with rilonacept

Rilonacept: 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

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

Total of all reporting groups
Overall Number of Baseline Participants 21 21 42
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 42 participants
61  (11) 65  (11) 63  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Female
5
  23.8%
5
  23.8%
10
  23.8%
Male
16
  76.2%
16
  76.2%
32
  76.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
White 16 16 32
Hispanic 6 6 12
African American 5 5 10
Etiology of CKD  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Hypertension 12 10 22
Type II Diabetes 10 9 19
Type I DIabetes 1 2 3
Autosomal Dominant Polycystic Kidney Disease 1 2 3
Renal Cell Carcinoma 0 3 3
Focal Segmental Glomerulosclerosis 1 0 1
Estimated glomerular filtration rate  
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73m^2
Number Analyzed 21 participants 21 participants 42 participants
38  (14) 38  (12) 38  (13)
1.Primary Outcome
Title Change in Flow-mediated Dilation (FMD)
Hide Description Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Time Frame 3 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rilonacept Placebo
Hide Arm/Group Description:

12 weeks of treatment with rilonacept

Rilonacept: 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

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

Overall Number of Participants Analyzed 18 19
Mean (Standard Deviation)
Unit of Measure: change in percent flow-mediated dilation
1.1  (3.2) -0.9  (2.2)
2.Secondary Outcome
Title Change in Aortic Pulse-wave Velocity (aPWV)
Hide Description Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Time Frame 3 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rilonacept Placebo
Hide Arm/Group Description:

12 weeks of treatment with rilonacept

Rilonacept: 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

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

Overall Number of Participants Analyzed 18 19
Mean (Standard Deviation)
Unit of Measure: change in pulse-wave velocity (cm/sec)
12  (65) 2  (71)
3.Secondary Outcome
Title Change in Contribution of Oxidative Stress to FMD
Hide Description 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.
Time Frame 3 months after start of treatment
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Hide Analysis Population Description
sub-group from Denver site
Arm/Group Title Rilonacept: Baseline Rilonacept: End of Study Placebo: Baseline Placebo: End of Study
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Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the rilonacept group at baseline.
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the rilonacept group at 12 weeks.
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
Overall Number of Participants Analyzed 10 7 13 10
Mean (Standard Deviation)
Unit of Measure: change in percent flow-mediated dilation
0.16  (2.52) 0.51  (2.24) -0.04  (1.96) 0.69  (1.73)
4.Other Pre-specified Outcome
Title Change in High-sensitivity C-reactive Protein (hsCRP)
Hide Description Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.
Time Frame 3 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rilonacept Placebo
Hide Arm/Group Description:

12 weeks of treatment with rilonacept

Rilonacept: 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

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

Overall Number of Participants Analyzed 16 19
Median (Inter-Quartile Range)
Unit of Measure: change in c-reactive protein (mg/L)
-1.02
(-2.9 to 1.3)
0.16
(-0.82 to 1.19)
5.Other Pre-specified Outcome
Title Change in Vascular Endothelial NADPH Oxidase Expression
Hide Description 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.
Time Frame 3 months after start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
sub-group from Denver site
Arm/Group Title Rilonacept Placebo
Hide Arm/Group Description:

12 weeks of treatment with rilonacept

Rilonacept: 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

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

Overall Number of Participants Analyzed 6 5
Mean (Standard Deviation)
Unit of Measure: absolute change in ratio
-0.02  (0.03) 0.01  (0.03)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rilonacept Placebo
Hide Arm/Group Description

12 weeks of treatment with rilonacept

Rilonacept: 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

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

All-Cause Mortality
Rilonacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Rilonacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   0/21 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Rilonacept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   5/21 (23.81%)   2/21 (9.52%) 
Infections and infestations     
Neck abscess/pyomyositis  1/21 (4.76%)  0/21 (0.00%) 
upper respiratory infection  3/21 (14.29%)  2/21 (9.52%) 
Skin and subcutaneous tissue disorders     
Injection site reaction  1/21 (4.76%)  1/21 (4.76%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Kristen Nowak
Organization: University of Colorado Anschutz Medical Campus
Phone: 303-724-4842
EMail: Kristen.Nowak@ucdenver.edu
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01663103    
Other Study ID Numbers: 12-0586
First Submitted: August 7, 2012
First Posted: August 13, 2012
Results First Submitted: April 6, 2016
Results First Posted: September 12, 2016
Last Update Posted: September 12, 2016