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© 2008 American Academy of Neurology Growth hormone secretagogue MK-677No clinical effect on AD progression in a randomized trialFrom Merck Research Laboratories (J.J.S., J.M.R., Y.P., C.R.L., M.L.N.), North Wales, PA; and Yale University School of Medicine (C.H.v.D.), New Haven, CT. Address correspondence and reprint requests to Dr. J. Sevigny, Merck Research Laboratories, 351 North Sumneytown Pike, North Wales, PA 19454 jeffrey_sevigny{at}merck.com. Background: In animals, insulin-like growth factor-1 (IGF-1) increases clearance of β-amyloid, a pathologic hallmark of Alzheimer disease (AD), from the CNS. Serum IGF-1 level decreases with age, and shows a further decrease in AD. We examined whether the growth hormone secretagogue MK-677 (ibutamoren mesylate), a potent inducer of IGF-1 secretion, slows the rate of progression of symptoms in patients with AD. Methods: A double-blind, multicenter study was conducted in which 563 patients with mild to moderate AD were randomized to receive MK-677 25 mg or placebo daily for 12 months. Efficacy measures were mean change from baseline at month 12 on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC-plus), the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating-sum of boxes (CDR-sob).
Results: A total of 416 patients completed treatment and assessments at 12 months. Administration of MK-677 25 mg resulted in a 60.1% increase in serum IGF-1 levels at 6 weeks and a 72.9% increase at 12 months. In mixed-effects models that included treatment, time (month), randomization strata (baseline MMSE score Conclusion: Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.
Abbreviations: AD = Alzheimer disease; ADAS-Cog = cognitive subscale of the Alzheimer's Disease Assessment Scale; ADCS-ADL = Alzheimer's Disease Cooperative Study-Activities of Daily Living; CDR = Clinical Dementia Rating; CDR-sob = Clinical Dementia Rating-sum of boxes; CIBIC-plus = Clinician's Interview Based Impression of Change with caregiver input; GH = growth hormone; IGF-1 = insulin-like growth factor-1; ITT = intention-to-treat; MMSE = Mini-Mental State Examination.
*Members of the MK-677 Protocol 30 Study Group are listed in the appendix. Disclosure: This study was funded by Merck Research Laboratories. Drs. Sevigny, Ryan, Peng, and Lines and Mr. Nessly are employees of Merck and own stock/stock options in Merck. Dr. van Dyck has received research funding and honoraria from Merck. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. Received May 7, 2008. Accepted in final form August 12, 2008. This article has been cited by other articles:
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20 vs >20), and interaction of treatment-by-time, there were no significant differences between the treatment groups on the CIBIC-plus or the mean change from baseline scores on the ADAS-Cog, ADCS-ADL, or CDR-sob scores over 12 months. 
