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

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ClinicalTrials.gov Identifier: NCT00420290
Recruitment Status : Completed
First Posted : January 11, 2007
Results First Posted : November 17, 2011
Last Update Posted : November 17, 2011
Sponsor:
Information provided by (Responsible Party):
Adriana Hung, Vanderbilt University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
End Stage Renal Disease Drug: kineret Drug: placebo Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients
Study Start Date : January 2008
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Kineret
Interleukin-1 receptor antagonist
Drug: kineret
100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks
Other Name: Anakinra
Placebo Comparator: Placebo Drug: placebo
100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Interleukin-6 (IL-6) [ Time Frame: month 1 ]
    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.

  2. Serum Prealbumin [ Time Frame: month 1 ]
    Prealbumin is a sensitive laboratory assay for serum levels of prealbumin, which is a biomarker of nutrition.

  3. Serum Albumin [ Time Frame: month 1 ]
    Albumin is a sensitive laboratory assay for serum levels of albumin, which is a biomarker of nutrition.

  4. Lean Body Mass (LBM) [ Time Frame: month 1 ]
    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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Patients with residual renal function > 5 ml/min or urine output > 100 ml/day;
  2. Pregnancy;
  3. 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);
  4. 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);
  5. Hospitalization within 1 month prior to the study;
  6. 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)];
  7. Patients receiving steroids and/or other immunosuppressive agents;
  8. Life-expectancy less than 6 months;
  9. Age greater than 75 or less than 18 years old;
  10. Hypersensitivity to organic nitrates, isosorbide, or nitroglycerin.
  11. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00420290


Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Adriana Hung, MD Vanderbilt University

Publications of Results:
Responsible Party: Adriana Hung, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00420290     History of Changes
Other Study ID Numbers: 060661
First Posted: January 11, 2007    Key Record Dates
Results First Posted: November 17, 2011
Last Update Posted: November 17, 2011
Last Verified: October 2011

Keywords provided by Adriana Hung, Vanderbilt University:
inflammation
end stage renal disease

Additional relevant MeSH terms:
Inflammation
Kidney Diseases
Kidney Failure, Chronic
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents