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

NCT ID: NCT00420290

Last Updated: 2011-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Kineret

Interleukin-1 receptor antagonist

Group Type: ACTIVE_COMPARATOR

kineret

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

Interventions

kineret

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

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

Anakinra

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Adriana Hung

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adriana Hung, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21310819 (View on PubMed)

Other Identifiers

060661

Identifier Type: -

Identifier Source: org_study_id