The objective of this study is to determine MK-0677 increases IGF-1 in patients with end stage renal disease (ESRD) on hemodialysis.
With development and progression of chronic kidney disease (CKD) to end stage renal disease (ESRD), malnutrition becomes an increasingly severe problem. This is thought to occur from two mechanisms: decreased appetite secondary to uremia and development of a catabolic inflammatory milieu. Patients experience decreased muscle mass and functional activity associated with increased morbidity and mortality. Many therapies to improve poor nutritional state have been used with little success. Growth hormone (GH) and insulin like growth hormone (IGF-1) improve muscle mass, quality of life, nutritional parameters, immune and physical functions but must be given parenterally and are limited by expense and patient compliance. Recently, the endogenous GH receptor secretagogue (GHRS) ghrelin has been shown to raise endogenous GH and improve food intake but must be given parenterally and is not available. The experimental drug MK-0677, a synthetic GHRS, ghrelin mimetic, which is given orally, has recently been shown to increase IGF-1 and muscle mass in the elderly. Its effects in CKD and ESRD are unknown. We will study the effects of MK-0677 on renal patients. Specifically, we hope to show that the drug increases IGF-1 in renal patients, and has similar effects to exogenous GH and IGF-1. Subjects will be ESRD hemodialysis patients. This protocol is an investigator-initiated, randomized, double-blind crossover, placebo-controlled pilot study. The study's primary outcome is IGF-1 levels for subjects. Secondary outcomes will be levels of cytokines, esterase, leptin, insulin, ghrelin, TNF-alpha, CRPs, IL-1, IL-6, IL-10, and adiponectin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
49
University of Virginia
Charlottesville, Virginia, United States
Change in IGF-1 After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the IGF-1 levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Acyl-Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention.
Change in Leptin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Leptin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Insulin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Insulin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Des-Acyl Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in TNF-alpha After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the TNF-alpha levels after the subject has been on intervention for 30 days compared to baseline levels.
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Time frame: Baseline and after 30 days of intervention
Change in CRPs After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the CRPs levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in IL-1 After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the IL-1 levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Changes in the Following Level: IL-6
Change in IL-6 after 30 days of intervention.
Time frame: After the subject has comleted their last visit
Change in IL-10 After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the IL-10 levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Esterase After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Esterase levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Adiponectin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Adiponectin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention
Change in Ghrelin After 30 Days of Intervention Compared to Baseline Level.
Looking for a change in the Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.
Time frame: Baseline and after 30 days of intervention