Clinical trial NCT00474279: Effects of an Oral GH Secretagogue (MK-677) on Body Composition and Functional Ability of Older Adults
Official title: Effects of an Oral GH Secretagogue (MK-677) on Body Composition and Functional Ability of Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Aging
Keywords: Growth hormone secretagogue
Body composition
Functional ability
Aging
Sarcopenia
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2007-05-16
Enrollment: 72
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether treatment of healthy older men and women with oral MK-677 for 12 months will enhance pulsatile GH release and increase mean GH and IGF-I concentrations into the range of young adults and will have favorable effects on body composition and functional ability on older adults.

Detailed description: This is a two year, double-blind, placebo-controlled cross-over trial of once daily administration of MK-677, an oral GH secretagogue, to healthy older adults. During the first year, subjects will be randomized to MK-677 or placebo treatment. In each of three subgroups of subjects (men, women off and women on hormone replacement therapy), 16 subjects will receive MK-677 and 8 will receive placebo. After 1 year, the subjects who received placebo will be switched to MK-677 treatment; the subjects who received MK-677 for the first year will be randomized to either placebo or MK-677 for the second year of the study.The study will test changes in GH, IGF-I, body composition and function.

Eligibility criteria: Inclusion Criteria:

* Healthy men and women  60 years of age, with a body mass index of \< 35 kg/m2.

Exclusion Criteria:

* Medication known to affect GH secretion, other than estrogen replacement therapy
* Coronary artery disease,
* Congestive heart failure,
* Peripheral vascular disease,
* Diabetes mellitus (requiring insulin or an oral hypoglycemic agent),
* Significant hypertension (BP \>180 systolic or \>100 diastolic at rest);
* Renal, hepatic, pulmonary disease;
* Untreated hypothyroidism, untreated hyperthyroidism;
* History of seizure disorder;
* History of malignancy (other than some skin cancers), history of active chronic infections (e.g., HIV, tuberculosis).
* Hematocrit \< 40%, men, \< 36%, women
* History of daily tobacco use within past 3 months
* Chronic alcohol abuse
* Strenuous exercise for average of more than 60 min/day
* Investigational drug within past 6 weeks
* Psychiatric history, especially anorexia nervosa
* Transmeridian travel within 2 weeks prior to or during study

Primary outcomes:
measure: At 12 months: 24-hour mean growth hormone concentrations
measure: Insulin-like growth factor-I concentrations
measure: Body weight and fat mass, specifically abdominal visceral fat
measure: Fat-free mass
measure: Safety determined by routine laboratory tests at 1 to 3 month intervals, yearly pap smears and mammograms
Secondary outcomes:
measure: at 12 months: Growth hormone secretory dynamics
measure: Isokinetic muscle strength (knee and shoulder)
measure: Thigh muscle cross-sectional area
measure: Function tests (timed walks, stair climb, chair rise)
measure: Quality of life assessments
measure: Insulin sensitivity
measure: Lipid profile
measure: Resting metabolic rate
measure: Aerobic exercise capacity
measure: Exploratory outcomes:
measure: effects of gender and HRT on primary outcomes
measure: effects of treatment in year 2: Year 2 outcomes include effects of continuation on MK-677, or crossover to placebo, placebo to MK-677
measure: bone mineral density at end of year 2.
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Michael O. Thorner, MBBS, DSc,
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO. 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 Dec;81(12):4249-57. doi: 10.1210/jcem.81.12.8954023.