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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Adriana Hung, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00420290
First received: January 10, 2007
Last updated: October 10, 2011
Last verified: October 2011
  Purpose

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 Intervention
End Stage Renal Disease
Drug: kineret
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: month 1 ] [ Designated as safety issue: No ]
    hsCRP is a sensitive laboratory assay for serum levels of C-reactive protein, which is a biomarker of inflammation.


Secondary Outcome Measures:
  • Interleukin-6 (IL-6) [ Time Frame: month 1 ] [ Designated as safety issue: No ]
    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.

  • Serum Prealbumin [ Time Frame: month 1 ] [ Designated as safety issue: No ]
    Prealbumin is a sensitive laboratory assay for serum levels of prealbumin, which is a biomarker of nutrition.

  • Serum Albumin [ Time Frame: month 1 ] [ Designated as safety issue: No ]
    Albumin is a sensitive laboratory assay for serum levels of albumin, which is a biomarker of nutrition.

  • Lean Body Mass (LBM) [ Time Frame: month 1 ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: January 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Publications:
Responsible Party: Adriana Hung, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00420290     History of Changes
Other Study ID Numbers: 060661
Study First Received: January 10, 2007
Results First Received: July 11, 2011
Last Updated: October 10, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Vanderbilt University:
inflammation
end stage renal disease

Additional relevant MeSH terms:
Inflammation
Kidney Diseases
Kidney Failure, Chronic
Pathologic Processes
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases

ClinicalTrials.gov processed this record on October 21, 2014