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

Sponsored by:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00420290

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.

Condition	Intervention
End Stage Renal Disease	Drug: kineret Drug: placebo

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients

Resource links provided by NLM:

MedlinePlus related topics: Dialysis Kidney Failure

Drug Information available for: Anakinra

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

A decrease in muscle protein breakdown [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

A change in C-reactive protein (CRP) and serum amyloid A levels [ Time Frame: 1 month ] [ Designated as safety issue: No ]
whole-body protein turnover rate [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	July 2007
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator	Drug: kineret 100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks
2: Placebo Comparator	Drug: placebo placebo 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:

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).

Exclusion Criteria:

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, HIV, liver disease);
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)];
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00420290

Contacts

Contact: Cindy Booker

615-343-5828

cindy.a.booker@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Cindy Booker 615-343-5828 cindy.a.booker@vanderbilt.edu
Principal Investigator: Adriana Hung, MD

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

Adriana Hung, MD

Vanderbilt University

More Information

No publications provided

Responsible Party:	Vanderbilt University Medical Center ( Adriana Hung, MD )
Study ID Numbers:	060661
Study First Received:	January 10, 2007
Last Updated:	June 17, 2009
ClinicalTrials.gov Identifier:	NCT00420290 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Vanderbilt University:

inflammation
end stage renal disease

Study placed in the following topic categories:

Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic

Kidney Diseases
Kidney Failure
Inflammation

Additional relevant MeSH terms:

Renal Insufficiency
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic

Kidney Failure, Chronic
Kidney Diseases
Kidney Failure
Inflammation

ClinicalTrials.gov processed this record on September 09, 2009