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

NCT00420290 | Completed Results DMC

• 1 other identifier: 060661
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Renal Disease

Keywords

inflammation; end stage renal disease

Outcome Measures

Primary Outcomes (1)

• 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.

  month 1

Secondary Outcomes (4)

• Interleukin-6 (IL-6)

  month 1

• Serum Prealbumin

  month 1

• Serum Albumin

  month 1

• Lean Body Mass (LBM)

  month 1

Study Arms (2)

Kineret

ACTIVE COMPARATOR

Interleukin-1 receptor antagonist

Drug: kineret

Placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

kineret DRUG

100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks

Also known as: Anakinra

Kineret

placebo DRUG

100 mg administered subcutaneously every other day (3 days a week during hemodialysis) for 4 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 \[recirculation and/or blood flow \< 500 ml/min for an arterial-venous graft (AVG) or \< 400 ml/min for an arterial-venous fistula (AVF)\];
• 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.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 21310819 RESULT

MeSH Terms

Conditions

Kidney Failure, Chronic; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

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.

Results Point of Contact

• Title: Adriana Hung, MD
• Organization: Vanderbilt University

adriana.hung@vanderbilt.edu

Study Officials

• Adriana Hung, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 10, 2007
• First Posted: January 11, 2007
• Study Start: January 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: November 17, 2011
• Results First Posted: November 17, 2011

Record last verified: 2011-10

Locations

US (1)