Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients
Status:
Completed
Trial end date:
2010-05-01
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center