Nutrition, Inflammation and Insulin Resistance in End Stage Renal Disease-Aim 2 (INSPIRED)
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|ClinicalTrials.gov Identifier: NCT02278562|
Recruitment Status : Completed
First Posted : October 30, 2014
Results First Posted : April 2, 2018
Last Update Posted : April 2, 2018
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).
|Condition or disease||Intervention/treatment||Phase|
|ESRD||Drug: anakinra Drug: actos Other: placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease|
|Actual Study Start Date :||October 22, 2014|
|Actual Primary Completion Date :||March 1, 2017|
|Actual Study Completion Date :||March 1, 2017|
Active Comparator: anakinra
100 mg of Anakinra in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months
100 mg in syringes; administered subcutaneously 3 times a week for 12 weeks (3 months)
Active Comparator: actos
Normal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and 30 mg of Actos in capsules administered orally 1 capsule per day for 3 months
30 mg capsules; administered orally 1 capsule per day for 12 weeks (3 months)
Placebo Comparator: placebo 1 and 2
Normal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months
placebo capsules and injection
- Change in Leucine Disposal Rate (LDR) [ Time Frame: baseline and 3 months ]LDR is a sensitive laboratory assessment of amino acid metabolism
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02278562
|United States, Tennessee|
|Tennessee Valley Healthcare System Nashville Campus, Nashville, TN|
|Nashville, Tennessee, United States, 37212-2637|
|Principal Investigator:||Talat A Ikizler, MD||Tennessee Valley Healthcare System Nashville Campus, Nashville, TN|