The Effects of MK-0677, an Oral Growth Hormone Secretagogue, in Patients with Hip Fracture

• Published in: Journal of the American Geriatrics Society (JAGS) Vol. 52; no. 4; pp. 516 - 523
• Main Authors: Bach, Mark A., Rockwood, Kenneth, Zetterberg, Carl, Thamsborg, Gorm, Hébert, Réjean, Devogelaer, Jean-Pierre, Christiansen, Jens Sandahl, Rizzoli, René, Ochsner, J.Lockwood, Beisaw, Norman, Gluck, Oscar, Yu, Leisure, Schwab, Thomas, Farrington, Jeanne, Taylor, Alice M., Ng, Jennifer, Fuh, Vivian
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Inc 01.04.2004; Blackwell; Wiley Subscription Services, Inc
• Subjects: Activities of Daily Living; Administration, Oral; Aged; Biological and medical sciences; Clinical trials; Double blind randomized controlled trials; Double-Blind Method; Drug therapy; Elderly people; Female; Fractured hips; Fractures; Functional performance; Geriatric Assessment; Geriatrics; Gerontology; Glucose - metabolism; Glycated Hemoglobin A - metabolism; Growth hormones; hip fracture; Hip Fractures - blood; Hip Fractures - drug therapy; Hip Fractures - physiopathology; Hip Fractures - rehabilitation; Hip joint; Hormones; Humans; Indoles - adverse effects; Indoles - pharmacology; Indoles - therapeutic use; Injuries of the limb. Injuries of the spine; Insulin - blood; Insulin-Like Growth Factor I - metabolism; Longitudinal Studies; Male; Medical sciences; Mental Competency; MK-0677; Older people; oral growth hormone secretagogue; Prescribing; Recovery; Recovery of Function; Safety; Sickness Impact Profile; Spiro Compounds - adverse effects; Spiro Compounds - pharmacology; Spiro Compounds - therapeutic use; Surveys and Questionnaires; Traumas. Diseases due to physical agents; Treatment Outcome; Human; Adenohypophyseal hormone; Diseases of the osteoarticular system; Somatotropin hormone; Oral administration; Fracture; Trauma; Elderly; Hip; Geriatrics
• ISSN: 0002-8614; 1532-5415
• DOI: 10.1111/j.1532-5415.2004.52156.x

Objectives: To evaluate the effects of MK‐0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals. Design: Placebo‐controlled, randomized, double‐blind trial. Setting: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers. Participants: One hundred sixty‐one hip‐fracture patients were enrolled. Entry criteria included consenting hip‐fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity. Intervention: Random assignment to 6 months of daily treatment with MK‐0677 or placebo. Patients were followed for an additional 6 months after completion of therapy. Measurements: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP‐NH), the ability to live independently, and insulin‐like growth factor I (IGF‐I) levels. Results: MK‐0677 treatment increased serum IGF‐I levels by 84% (95% confidence interval (CI)=63–107), compared with an increase of 17% (95% CI=8–28) on placebo. There were no significant differences between MK‐0677 and placebo in improvement in functional performance measures or in the overall SIP‐NH score. Although MK‐0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant. Conclusion: Although MK‐0677 treatment increased serum IGF‐I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip‐fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.