Nutrition, Inflammation and Insulin Resistance in End Stage Renal Disease-Aim 2
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease, Renal Impairment / Chronic Kidney Disease, Endocrine |
| Therapuetic Areas: | Endocrinology, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 4/17/2018 |
| Start Date: | October 22, 2014 |
| End Date: | March 1, 2017 |
Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease
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).
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).
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.
We found this trial at
1
site
Nashville, Tennessee 37212
Principal Investigator: Talat A Ikizler, MD
Phone: 615-343-5828
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