Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial

Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial / Ralf Nass, Suzan S. Pezzoli, Mary Clancy Oliveri, James T. Patrie, Frank E. Harrell Jr, Jody L. Clasey, Steven B. Heymsfield, Mark A. Bach, Mary Lee Vance, Michael O. Thorner. - (Annals of Internal Medicine 149 (2008) 9 (4 November); p. 601-611)

  • PMID: 18981485
  • PMCID: PMC2757071
  • DOI: 10.7326/0003-4819-149-9-200811040-00003


Abstract

Background: Growth hormone secretion and muscle mass decline from midpuberty throughout life, culminating in sarcopenia, frailty, decreased function, and loss of independence. The decline of growth hormone in the development of sarcopenia is one of many factors, and its etiologic role needs to be demonstrated.

Objective: To determine whether MK-677, an oral ghrelin mimetic, increases growth hormone secretion into the young-adult range without serious adverse effects, prevents the decline of fat-free mass, and decreases abdominal visceral fat in healthy older adults.

Design: 2-year, double-blind, randomized, placebo-controlled, modified-crossover clinical trial.

Setting: General clinical research center study performed at a university hospital.

Participants: 65 healthy adults (men, women receiving hormone replacement therapy, and women not receiving hormone replacement therapy) ranging from 60 to 81 years of age.

Intervention: Oral administration of MK-677, 25 mg, or placebo once daily.

Measurements: Growth hormone and insulin-like growth factor I levels. Fat-free mass and abdominal visceral fat were the primary end points after 1 year of treatment. Other end points were body weight, fat mass, insulin sensitivity, lipid and cortisol levels, bone mineral density, limb lean and fat mass, isokinetic strength, function, and quality of life. All end points were assessed at baseline and every 6 months.

Results: Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, -0.5 kg [95% CI, -1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, -1.0 kg [CI, -2.1 to 0.2 kg] vs. 0.8 kg [CI, -0.1 to 1.6 kg], respectively; P = 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001). Body weight increased 0.8 kg (CI, -0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P = 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased. The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, -0.14 mmol/L [CI, -0.27 to -0.01 mmol/L]; -5.4 mg/dL [CI, -10.4 to -0.4 mg/dL]; P = 0.026); no differences between groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 microg/dL [CI, 1.0 to 2.6 microg/dL]) in MK-677 recipients (P = 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.

Limitation: Study power (duration and participant number) was insufficient to evaluate functional end points in healthy elderly persons.

Conclusion: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.

Original document

Parameters

Science
Study
Date
4 November 2008
People
Bach, Mark A.
Clasey, Jody L.
Harrell Jr., Frank E.
Heymsfield, Steven B.
Nass, Ralf
Oliveri, Mary Clancy
Patrie, James T.
Pezzoli, Suzan S.
Thorner, Michael O.
Vance, Mary Lee
Country
United States of America
Language
English
Other organisations
University of Kentucky (UKY)
University of Virginia (UVA)
Vanderbilt University (VU)
Doping classes
S2. Peptide Hormones, Growth Factors
Substances
Lenomorelin (ghrelin)
Medical terms
Health effects
Document category
Scientific article
Document type
Pdf file
Date generated
28 September 2021
Date of last modification
20 October 2021
Category
  • Legal Source
  • Education
  • Science
  • Statistics
  • History
Country & language
  • Country
  • Language
Other filters
  • ADRV
  • Legal Terms
  • Sport/IFs
  • Other organisations
  • Laboratories
  • Analytical aspects
  • Doping classes
  • Substances
  • Medical terms
  • Various
  • Version
  • Document category
  • Document type
Publication period
Origin