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Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML, MK-677 Protocol 30 Study Group.. Neurology, 2008-11-01
Topic: Brain proteins, microglia and lab models
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 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.
Key findings
- Results A total of 416 patients completed treatment and assessments 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.
Why it matters
In this double-blind, multicenter trial of 563 patients with mild to moderate Alzheimer disease, MK-677 increased serum IGF-1 levels but showed no significant differences from placebo on the CIBIC-plus or on change from baseline scores on the ADAS-Cog, ADCS-ADL, or CDR-sob. The treatment had no clinical effect on AD progression.
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Study details
- Participants563
- Effect size60.1%; 72.9%
- Evidence strengthHigh
How this study scored 69/100
Published in a leading specialty journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 563 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 91 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 3.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Michael L. Nessly: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19015485) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Sevigny, J. J., Ryan, J. M., van Dyck, C. H., Peng, Y., Lines, C. R., Nessly, M. L., et al. (2008). Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. https://doi.org/10.1212/01.wnl.0000335163.88054.e7
Vancouver
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. 2008. doi:10.1212/01.wnl.0000335163.88054.e7. PMID: 19015485.
BibTeX
@article{sevigny2008-19015485,
author = {Sevigny, J. J. and Ryan, J. M. and van Dyck, C. H. and Peng, Y. and Lines, C. R. and Nessly, M. L. and {MK-677 Protocol 30 Study Group}},
title = {{Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial}},
journal = {Neurology},
year = {2008},
doi = {10.1212/01.wnl.0000335163.88054.e7},
pmid = {19015485},
url = {https://doi.org/10.1212/01.wnl.0000335163.88054.e7}
}
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