Nutrition, Inflammation and Insulin Resistance in End Stage Renal Disease-Aim 2

ESRD Clinical Trial

— INSPIRED  

Official title:

Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02278562
• Other study ID #: NEPH-011-11S
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2014
• Last updated: March 29, 2018
• Start date: October 22, 2014
• Est. completion date: March 1, 2017

Study information

• Verified date: March 2018
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

By 2030 an estimated 2 million people in the US will need dialysis or transplantation for advanced kidney failure. An even more disturbing statistic is that mortality in End Stage Renal Disease (ESRD) is six times higher than in the general Medicare population with adjustment for age, gender and ethnicity. Protein energy wasting is highly prevalent in these patients and is one of the most important determinants of their poor clinical outcome.

Despite its well-recognized occurrence, the etiology and the mechanisms leading to protein energy wasting observed in chronic hemodialysis patients cannot be attributed to any single factor. However, irrespective of the specific etiologic mechanisms, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis (47).

Two well-recognized and presumably interrelated metabolic abnormalities, insulin resistance and chronic inflammation, may be the major determinants of protein catabolism in coronary heart disease (CHD) patients. There are no studies examining the effects of anti-inflammatory interventions and/or insulin sensitizers on protein homeostasis in CHD. Due to their established anti-inflammatory and other pleiotropic effects, Interleukin-1 receptor antagonist Anakinra and insulin sensitizer peroxisome proliferator-activated receptors (PPAR) agonist Actos represent two such promising interventions. By modulating inflammatory response and insulin signaling through two pharmacological interventions, the investigators will have the unique opportunity to clarify mechanisms contributing of these two particular metabolic derangements in the development of protein energy wasting observed in chronic hemodialysis patients.

The overall goal is to elucidate the mechanisms by which chronic inflammation and insulin resistance influence the development of protein energy wasting in hemodialysis patients.

Specific Aim: To test the hypothesis that inhibiting inflammatory response by administration of an Interleukin1receptor antagonist (Anakinra) or increasing insulin sensitivity by administration of a PPAR agonist (Actos) will improve net protein metabolism.

Hypothesis: The chronic inflammatory component of protein energy wasting (PEW) observed in hemodialysis patients is, at least in part, mediated by insulin resistance.

Interim analysis may be performed (no specific plan at this time).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 1, 2017
• Est. primary completion date: March 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Patients on CHD undergoing three time a week therapy for more than 6 months;

• Age 21 years old;

• Acceptable dialysis adequacy (spKt/V > 1.2);

• A patent, well-functioning, arterio-venous dialysis access;

• Ability to give informed consent;

• Life expectancy greater than 6 months;

• BMI >=20 and <=45.

Exclusion Criteria:

• Pregnancy;

• Intolerance or allergy to the study medication (including the metabolic clamp studies);

• Severe, unstable, active inflammatory disease (active infection, active connective tissue disorder), active cancer or cancer history in the prior 5 years except skin cancer, AIDS-HIV, active or history of liver disease (including hepatitis B virus and hepatitis C virus);

• Hospitalization or infection within 1 month prior to the study;

• Patients receiving steroids and/or other immunosuppressive agents (Prednisone > 5 mg/day; excluding inhaled and topical steroids);

• Diabetes Mellitus on insulin therapy;

• Previous history of tuberculosis (TB) with or without documented adequate therapy;

• Patients with recent close exposure to an individual with active TB;

• Females using oral contraceptives;

• Patients with New York Heart Association (NYHA) Class III or IV heart failure;

• Patients with a history of angina, myocardial infarction, transient ischemic attacks, or strokes within the last 6 months.

Related Conditions & MeSH terms

• ESRD
• Inflammation
• Insulin Resistance
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• anakinra
100 mg in syringes; administered subcutaneously 3 times a week for 12 weeks (3 months)
• actos
30 mg capsules; administered orally 1 capsule per day for 12 weeks (3 months)

Other:
• placebo
placebo capsules and injection

Locations

Country	Name	City	State
United States	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Leucine Disposal Rate (LDR)	LDR is a sensitive laboratory assessment of amino acid metabolism	baseline and 3 months
Secondary	Change in Whole-body Net Protein Balance	Whole-body net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the whole body	baseline and 3 months
Secondary	Change in Skeletal Muscle Net Protein Balance	Skeletal muscle net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the skeletal muscles.	baseline and 3 months