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

Annals of Internal Medicine

Volumn 149, Issue 9, 2008, Pages 601-611

  Nass, Ralf ^a   Pezzoli, Suzan S ^a   Oliveri, Mary Clancy ^a   Patrie, James T ^a   Harrell Jr , Frank E ^b   Clasey, Jody L ^c   Heymsfield, Steven B ^d   Bach, Mark A ^d   Vance, Mary Lee ^a   Thorner, Michael O ^a  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF KENTUCKY   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROCORTISONE; IBUTAMOREN; INSULIN; LIPID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; SOMATOMEDIN C; HUMAN GROWTH HORMONE; INDOLE DERIVATIVE; SOMATOMEDIN BINDING PROTEIN 1; SPIRO COMPOUND;

ABDOMINAL FAT; ADULT; AGED; APPETITE; ARTHRALGIA; ARTICLE; BODY COMPOSITION; BODY FAT; BODY WEIGHT; BONE DENSITY; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; COLON CANCER; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIET RESTRICTION; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG TOLERABILITY; FEMALE; FOLLOW UP; FRAIL ELDERLY; FUNCTIONAL ASSESSMENT; GLUCOSE BLOOD LEVEL; GROUPS BY AGE; GROWTH HORMONE RELEASE; HEART INFARCTION; HORMONE SUBSTITUTION; HUMAN; HYDROCORTISONE BLOOD LEVEL; INNER CELL MASS; INSULIN SENSITIVITY; INTRAABDOMINAL FAT; INTRACELLULAR SPACE; LABORATORY TEST; LEG EDEMA; LIMB; LIPID BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MAMMOGRAPHY; MORNING DOSAGE; MUSCLE ATROPHY; MUSCLE MASS; MUSCLE STRENGTH; MYALGIA; PAPANICOLAOU TEST; PATIENT COMPLIANCE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SUBCUTANEOUS FAT; TESTOSTERONE BLOOD LEVEL; TONGUE CARCINOMA; TOTAL BODY WATER; TREATMENT OUTCOME; UNIVERSITY HOSPITAL; ADIPOSE TISSUE; BLOOD; HISTOLOGY; METABOLISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; PATIENT EDUCATION; SECRETION; SKELETAL MUSCLE; THIGH; CHEMICALLY INDUCED DISORDER; PAIN;

ADIPOSE TISSUE; ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; BLOOD GLUCOSE; BODY COMPOSITION; DOUBLE-BLIND METHOD; FEMALE; HUMAN GROWTH HORMONE; HUMANS; INDOLES; INSULIN; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 1; MALE; MIDDLE AGED; MUSCLE, SKELETAL; SPIRO COMPOUNDS; THIGH; APPETITE; PAIN;

EID: 55749097801     PISSN: 00034819     EISSN: 15393704     Source Type: Journal    
DOI: 10.7326/0003-4819-149-9-200811040-00003     Document Type: Article

References (48)

1. Fantin F, Di Francesco V, Fontana G, Zivelonghi A, Bissoli L, Zoico E, et al. Longitudinal body composition changes in old men and women: interrelationships with worsening disability. J Gerontol A Biol Sci Med Sci. 2007;62:1375-81. [PMID: 18166688]
2. Kotler DP, Tierney AR, Wang J, Pierson RN Jr. Magnitude of body-cellmass depletion and the timing of death from wasting in AIDS. Am J Clin Nutr. 1989;50:444-7. [PMID: 2773823]
3. Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol. 2000;89: 81-8. [PMID: 10904038]
4. Zadik Z, Chalew SA, McCarter RJ Jr, Meistas M, Kowarski AA. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab. 1985;60:513-6. [PMID: 3972964]
5. Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest. 1981;67:1361-9. [PMID: 7194884]
6. Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism. 1991;40:1323-6. [PMID: 1961129]
7. DeNino WF, Tchernof A, Dionne IJ, Toth MJ, Ades PA, Sites CK, et al. Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care. 2001;24: 925-32. [PMID: 11347756]
8. Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146:104-15. [PMID: 17227934]
9. Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, et al. Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab. 1996;81:4249-57. [PMID: 8954023]
10. Smith RG. Development of growth hormone secretagogues. Endocr Rev. 2005;26:346-60. [PMID: 15814848]
11. Veldhuis JD, Johnson ML. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986;250:E486-93. [PMID: 3008572]
12. Johnson ML, Veldhuis PP, Farhi LS, Evans WS. Performance properties of an automatic multi-parameter deconvolution method (AutoDecon). Paper presented at 88th Meeting of the Endocrine Society. Boston, MA, 26 June 2006. Poster session 3, p 459.
13. Heymsfield SB, Lichtman S, Baumgartner RN, Wang J, Kamen Y, Aliprantis A, et al. Body composition of humans: comparison of two improved four-compartment models that differ in expense, technical complexity, and radiation exposure. Am J Clin Nutr. 1990;52:52-8. [PMID: 2360552]
14. Clasey JL, Kanaley JA, Wideman L, Heymsfield SB, Teates CD, Gutgesell ME, et al. Validity of methods of body composition assessment in young and older men and women. J Appl Physiol. 1999;86:1728-38. [PMID: 10233141]
15. Heymsfield SB, Smith R, Aulet M, Bensen B, Lichtman S, Wang J, et al. Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry. Am J Clin Nutr. 1990;52:214-8. [PMID: 2375286]
16. Gallagher D, Visser M, De Meersman RE, Sepúlveda D, Baumgartner RN, Pierson RN, et al. Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J Appl Physiol. 1997;83:229-39. [PMID: 9216968]
17. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147:755-63. [PMID: 9554417]
18. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147:755-63. [PMID: 9554417]
19. Clasey JL, Bouchard C, Wideman L, Kanaley J, Teates CD, Thorner MO, et al. The influence of anatomical boundaries, age, and sex on the assessment of abdominal visceral fat. Obes Res. 1997;5:395-401. [PMID: 9385612]
20. Silva AM, Wang J, Pierson RN Jr, Wang Z, Heymsfield SB, Sardinha LB, et al. Extracellular water: greater expansion with age in African Americans. J Appl Physiol. 2005;99:261-7. [PMID: 15731394]
21. Schoeller DA, van Santen E, Peterson DW, Dietz W, Jaspan J, Klein PD. Hydrometry. In: Roche AF, Heymsfield SB, Lohman TG, eds. Human Body Composition. Champaign, IL: Human Kinetics; 1996:25-49.
22. Plotkin D, Ng J, Farmer M, Gelato M, Kaiser F, Kiel D, et al. Use of MK-677, an oral GH secretagogue, in frail elderly subjects. Endocrinol Metab. 1997;4(Suppl A):35-36.
23. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402-10. [PMID: 10902785]
24. Tabachnick BG, Fidell LS. Using Multivariate Statistics. 5th ed. New York: Pearson Education; 2007.
25. Wang Z, St-Onge MP, Lecumberri B, Pi-Sunyer FX, Heshka S, Wang J, et al. Body cell mass: model development and validation at the cellular level of body composition. Am J Physiol Endocrinol Metab. 2004;286:E123-8. [PMID: 14532167]
26. Morley JE. Weight loss in older persons: new therapeutic approaches. Curr Pharm Des. 2007;13:3637-47. [PMID: 18220800]
27. Morley JE. Anorexia and weight loss in older persons [Editorial]. J Gerontol A Biol Sci Med Sci. 2003;58:131-7. [PMID: 12586850]
28. Bengtsson BA, Edén S, Lönn L, Kvist H, Stokland A, Lindstedt G, et al. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab. 1993;76:309-17. [PMID: 8432773]
29. Franco C, Brandberg J, Lönn L, Andersson B, Bengtsson BA, Johannsson G. Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. J Clin Endocrinol Metab. 2005;90:1466-74. [PMID: 15598680]
30. Münzer T, Harman SM, Hees P, Shapiro E, Christmas C, Bellantoni MF, et al. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab. 2001;86:3604-10. [PMID: 11502785]
31. Götherström G, Bengtsson BA, Sunnerhagen KS, Johannsson G, Svensson J. The effects of five-year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients. Clin Endocrinol (Oxf). 2005;62:105-13. [PMID: 15638878]
32. Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, et al. Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med. 1996;124:708-16. [PMID: 8633830]
33. Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA. 2002;288:2282-92. [PMID: 12425705]
34. Buchner DM, Larson EB, Wagner EH, Koepsell TD, de Lateur BJ. Evidence for a non-linear relationship between leg strength and gait speed. Age Ageing. 1996;25:386-91. [PMID: 8921145]
35. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56: M146-56. [PMID: 11253156]
36. Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/ National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc. 2006;54:991-1001. [PMID: 16776798]
37. Thomas DR. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clin Nutr. 2007;26:389-99. [PMID: 17499396]
38. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999; 341:1097-105. [PMID: 10511607]
39. Murden RA, Ainslie NK. Recent weight loss is related to short-term mortality in nursing homes. J Gen Intern Med. 1994;9:648-50. [PMID: 7853074]
40. Ryan C, Bryant E, Eleazer P, Rhodes A, Guest K. Unintentional weight loss in long-term care: predictor of mortality in the elderly. South Med J. 1995;88: 721-4. [PMID: 7597475]
41. del Rincon JP, Iida K, Gaylinn BD, McCurdy CE, Leitner JW, Barbour LA, et al. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes. 2007;56:1638-46. [PMID: 17363744]
42. Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, et al. MK-677/Alendronate Study Group. Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab. 2001;86:1116-25. [PMID: 11238495]
43. Svensson J, Lönn L, Jansson JO, Murphy G, Wyss D, Krupa D, et al. Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab. 1998;83:362-9. [PMID: 9467542]
44. Götherström G, Bengtsson BA, Bosaeus I, Johannsson G, Svensson J. Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency. Eur J Endocrinol. 2007;156:55-64. [PMID: 17218726]
45. Landin-Wilhelmsen K, Nilsson A, Bosaeus I, Bengtsson BA. Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized placebo-controlled trial. J Bone Miner Res. 2003;18:393-405. [PMID: 12619921]
46. Chapman IM, Hartman ML, Straume M, Johnson ML, Veldhuis JD, Thorner MO. Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab. 1994;78:1312-9. [PMID: 8200931]
47. Weltman A, Despres JP, Clasey JL, Weltman JY, Wideman L, Kanaley J, et al. Impact of abdominal visceral fat, growth hormone, fitness, and insulin on lipids and lipoproteins in older adults. Metabolism. 2003;52:73-80. [PMID: 12524665]
48. Després JP, Gagnon J, Bergeron J, Couillard C, Leon AS, Rao DC, et al. Plasma post-heparin lipase activities in the HERITAGE Family Study: the reproducibility, gender differences, and associations with lipoprotein levels. Health, risk factors, exercise training and genetics. Clin Biochem. 1999;32:157-65. [PMID: 10383074]