Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology 2008 Nov 18;71(21):1702-8
Date
11/19/2008Pubmed ID
19015485DOI
10.1212/01.wnl.0000335163.88054.e7Scopus ID
2-s2.0-58149260966 (requires institutional sign-in at Scopus site) 77 CitationsAbstract
BACKGROUND: In animals, insulin-like growth factor-1 (IGF-1) increases clearance of beta-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 < or =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.
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.
Author List
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML, MK-677 Protocol 30 Study GroupAuthor
Piero G. Antuono MD Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Activities of Daily LivingAged
Aged, 80 and over
Alzheimer Disease
Antipsychotic Agents
Confidence Intervals
Disease Progression
Double-Blind Method
Female
Humans
Indoles
Insulin-Like Growth Factor I
Male
Psychiatric Status Rating Scales
Spiro Compounds
Time Factors
Treatment Outcome
