End Stage Renal DiseaseNCT00420290

Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients

A study testing kineret in people with End Stage Renal Disease, run by Vanderbilt University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: End Stage Renal Disease
What is being tested?: kineret
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteUnited States
Study dates: Jan 2008to May 2010
Phase: Interventional
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients on CHD for more than 3 months;
Ability to read and sign the consent form;
Have acceptable dialysis adequacy (Kt/V > 1.2);
Use biocompatible hemodialysis membrane;
Have a patent, well functioning, arteriovenous dialysis access;
Signs of chronic inflammation (the average of three consecutive CRP measurements ≥ 5 mg/L).

Who cannot join

Patients with residual renal function > 5 ml/min or urine output > 100 ml/day;
Pregnancy;
Intolerance to the study medication or contraindication to the study medication: Hypersensitivity to E. coli-derived proteins, anakinra, or any component of the formulation; patients with active infections (including chronic or local infection);
Severe, unstable, active, or chronic inflammatory disease (active infection, active connective tissue disorder, active cancer or cancer history in the prior 5 years, HIV, liver disease including positive test or history of Hepatitis B or C);
Hospitalization within 1 month prior to the study;
Malfunctioning arterial-venous vascular access [recirculation and/or blood flow < 500 ml/min for an arterial-venous graft (AVG) or < 400 ml/min for an arterial-venous fistula (AVF)];

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Patients receiving steroids and/or other immunosuppressive agents;
Life-expectancy less than 6 months;
Age greater than 75 or less than 18 years old;
Hypersensitivity to organic nitrates, isosorbide, or nitroglycerin.
Presence of active infections or a history of pulmonary TB infection with or without documented adequate therapy. Subjects with current active TB, or recent close exposure to an individual with active TB, are excluded from the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University Medical Center
Nashville, Tennessee, 37232

Other trials in United States

About this study

Chronic hemodialysis (CHD) patients display multiple metabolic abnormalities related to advanced uremia. Despite vigorous attempts to prevent these abnormalities and their consequences, most CHD patients suffer from a unique form of nutritional derangement, which can be termed as "uremic wasting". Several studies have demonstrated that the presence of uremic wasting, especially the degree of loss of muscle mass, sharply increases mortality and hospitalization rate in CHD patients.

Several factors have been thought to be associated with uremic wasting, including hormonal derangement, anorexia, physical inactivity, and concurrent illnesses. Chronic inflammation, also highly prevalent in these patients, causes muscle catabolism in animal models and certain clinical conditions. Epidemiological studies show an association between chronic inflammation and uremic wasting in hemodialysis patients indicating a possible causal relationship.

The cause for the activated inflammatory state in CHD patients is believed to be multi-factorial. Nevertheless, it is certainly important for the host to limit its biological activity by eliciting a stronger anti-inflammatory response, for example through the production of naturally occurring receptor antagonist. Interleukin 1 beta, one of the major pro-inflammatory cytokines has been shown to be associated with protein catabolism in several chronic disease states, including advanced uremia. A balance between interleukin 1 beta (agonist) and its naturally occurring receptor antagonist IL-1ra may play a pivotal role in controlling the inflammatory response and its consequences in this population.

The overall goal of this particular grant application is to examine the short-term effects of the administration of the recombinant form of IL-1ra on 1) chronic inflammatory state and 2) protein homeostasis in chronically inflamed CHD patients.

We have updated our protocol to perform an interim analysis. The interim analysis will be performed after half of the planned study sample has been enrolled (14 subjects; 7 in each arm). The interim analysis has been approved by the Data Safety Monitoring Board.

Conditions: End Stage Renal Disease
Being tested: kineret, placebo
Keywords: inflammation, end stage renal disease
Medical subject headings: Kidney Failure, Chronic, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

kineretDrug
Also called Anakinra
100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks
placeboDrug
100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks

Study groups in NCT00420290
Study group	Role	What they receive
Kineret	Active comparator	Interleukin-1 receptor antagonist Receives: Drug: kineret
Placebo	Placebo comparator	Not described Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

High Sensitivity C-reactive Protein (hsCRP)
hsCRP is a sensitive laboratory assay for serum levels of C-reactive protein, which is a biomarker of inflammation.
Measured: month 1

Secondary outcomes (4)

Interleukin-6 (IL-6)
IL-6 is a sensitive laboratory assay for serum levels of interlukin-6, which is a pro-inflammatory cytokine that is used to evaluate the inflammatory response.
Measured: month 1
Serum Prealbumin
Prealbumin is a sensitive laboratory assay for serum levels of prealbumin, which is a biomarker of nutrition.
Measured: month 1
Serum Albumin
Albumin is a sensitive laboratory assay for serum levels of albumin, which is a biomarker of nutrition.
Measured: month 1
Lean Body Mass (LBM)
LBM is a measurement of body composition in terms of lean body mass as determined using Dual Energy X-ray Absorptiometry (DEXA) performed 1 to 2 hours after dialysis.
Measured: month 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008May 2010

First posted11 Jan 2007 (estimated)
Study startJan 2008
Primary completionMay 2010
Study completionMay 2010

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00420290
Sponsor's protocol ID: 060661
Status last verified: Oct 2011
First submitted: 10 Jan 2007
Last updated: 17 Nov 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Hung AM, Ellis CD, Shintani A, Booker C, Ikizler TA. IL-1beta receptor antagonist reduces inflammation in hemodialysis patients. J Am Soc Nephrol. 2011 Mar;22(3):437-42. doi: 10.1681/ASN.2010070760. Epub 2011 Feb 10.
PubMed 21310819

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All End Stage Renal Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients
ClinicalTrials.gov ID: NCT00420290
Acronym / sponsor ID: 060661
Conditions: End Stage Renal Disease
Keywords: inflammation, end stage renal disease
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Vanderbilt UniversityUniversity, hospital or other
Study start: Jan 2008
Primary completion: May 2010 (actual)
Study completion: May 2010 (actual)
First posted: 11 Jan 2007 (estimated)
Results: Posted 17 Nov 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Kineret	Active comparator	Drug: kineretInterleukin-1 receptor antagonist
Placebo	Placebo comparator	Drug: placebo

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Patients on CHD for more than 3 months;
Ability to read and sign the consent form;
Have acceptable dialysis adequacy (Kt/V > 1.2);
Use biocompatible hemodialysis membrane;
Have a patent, well functioning, arteriovenous dialysis access;

Key exclusion criteria (11 listed)

Patients with residual renal function > 5 ml/min or urine output > 100 ml/day;
Pregnancy;
Intolerance to the study medication or contraindication to the study medication: Hypersensitivity to E. coli-derived proteins, anakinra, or any component of the formulation; patients with active infections (including chronic or local infection);
Severe, unstable, active, or chronic inflammatory disease (active infection, active connective tissue disorder, active cancer or cancer history in the prior 5 years, HIV, liver disease including positive test or history of Hepatitis B or C);
Hospitalization within 1 month prior to the study;

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
kineretAlso: Anakinra100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks	Drug	Kineret
placebo100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks	Drug	Placebo

Primary outcome

High Sensitivity C-reactive Protein (hsCRP)
Time frame: month 1
hsCRP is a sensitive laboratory assay for serum levels of C-reactive protein, which is a biomarker of inflammation.

4 secondary outcomes

Interleukin-6 (IL-6)
Time frame: month 1
Serum Prealbumin
Time frame: month 1
Serum Albumin
Time frame: month 1
Lean Body Mass (LBM)
Time frame: month 1

Results and safety

Results posted to the registry on 17 Nov 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Kineret	11	7
Placebo	11	7

Primary outcome: High Sensitivity C-reactive Protein (hsCRP)

Time frame: month 1. Mean (Standard Deviation). Unit: mg/dl

Measure	Kineret n = 7	Placebo n = 7
Value	4.67 (2.87)	15.11 (10.18)

Kineret vs Placebo: p = 0.008, ANCOVA

Population analysed: The number of participants for analysis was based on those subjects who completed the 4-week study. The analysis was per protocol.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 month. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Kineret	0 of 7 (0%)	4 of 7 (57.1%)	Not reported
Placebo	0 of 7 (0%)	3 of 7 (42.9%)	Not reported

Limitations and caveats (from the sponsor): The sample size is small and the intervention is of short duration. Also, the results cannot be generalized to all CHD patients because our inclusion criteria were stringent.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21310819Hung AM, Ellis CD, Shintani A, Booker C, Ikizler TA. IL-1beta receptor antagonist reduces inflammation in hemodialysis patients. J Am Soc Nephrol. 2011 Mar;22(3):437-42. doi: 10.1681/ASN.2010070760. Epub 2011 Feb 10.

Related trials for End Stage Renal Disease

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Recruiting
Guiding Optimal Blood Pressure Management in Peritoneal Dialysis Pilot Trial
End Stage Kidney Disease (ESKD), Hypertension (HTN)
RecruitingObservational study
Physical Impairments in Children With Chronic Renal Failure
Chronic Kidney Failure, Chronic Kidney Diseases
RecruitingPhase 1
A Study to Test the Safety of the Study Drug Fosmanogepix and How the Body Handles It in Adults With Severe Kidney Failure on Dialysis
End Stage Renal Disease on Dialysis, Adult

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.

Adriana Hung, MD principal investigator

Vanderbilt University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing kineret in people with End Stage Renal Disease, run by Vanderbilt University at 1 site 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 6 inclusion and 11 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 17 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Nov 2011). 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?

High Sensitivity C-reactive Protein (hsCRP) (time frame: month 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00420290, which also lists 1 linked publication.

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 17 Nov 2011.