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NCT Number: NCT02278562

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

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).

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Key information

Conditions

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

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Anakinra

Drug

100 mg in syringes; administered subcutaneously 3 times a week for 12 weeks (3 months)

Actos

Drug

30 mg capsules; administered orally 1 capsule per day for 12 weeks (3 months)

Placebo

Other

placebo capsules and injection

Primary outcomes

  1. Change in Leucine Disposal Rate (LDR)

    Time frame: baseline and 3 months

    LDR is a sensitive laboratory assessment of amino acid metabolism

Secondary outcomes

  1. Change in Whole-body Net Protein Balance

    Time frame: baseline and 3 months

    Whole-body net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the whole body

  2. Change in Skeletal Muscle Net Protein Balance

    Time frame: baseline and 3 months

    Skeletal muscle net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the skeletal muscles.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Registry information

Official study title

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

Acronym: INSPIRED

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Oct 30, 2014
Registry last updated
Feb 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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