Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study.
Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials.



We performed a randomized crossover double-blind study in assessing the effect of MK-0677 versus placebo on IGF-1 levels, the primary outcome, in hemodialysis patients. In total, 26 subjects enrolled and 22 completed the 3-month crossover study.



The geometric mean IGF-1 was 1.07-fold greater [95% confidence interval (CI) 0.89-1.27; P = 0.718] after placebo. In patients receiving MK-0677, the geometric mean IGF-1 were 1.76-fold greater (95% CI 1.48-2.10; P < 0.001) following MK-0677. When the data were adjusted for preintervention IGF-1 concentration, the ratio of geometric means (MK-0677 relative to placebo) for the pre- versus postintervention change in the IGF-1 was 1.65 (95% CI 1.33-2.04; P < 0.001). These data demonstrate a 65% greater increase (95% CI 33-104%) in IGF-1 in MK-0677-dosed subjects compared with placebo. There were no serious adverse effects attributable to MK-0677.



MK-0677 increased serum IGF-1 levels with minimal adverse effects in hemodialysis subjects. Studies are needed to evaluate whether long-term therapy with MK-0677 improves PEW, lean body mass, physical strength, quality of life and survival in CKD/ESRD patients.
Division of Nephrology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
Garland A
GA
Campbell
PBHS Public Health Sciences Administration, Public Health Sciences, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
James T
JT
Patrie
Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
Bruce D
BD
Gaylinn
Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
Michael O
MO
Thorner
Division of Nephrology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
Warren K
WK
Bolton
D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011788:Quality of Life; D054440:Receptors, Ghrelin / Q000819:agonists*; D006435:Renal Dialysis; D013141:Spiro Compounds / Q000008:administration & dosage*
C583557:IGF1 protein, human; D007211:Indoles; D054440:Receptors, Ghrelin; D013141:Spiro Compounds; D007334:Insulin-Like Growth Factor I; C094817:ibutamoren mesylate