Growth hormone secretagogue MK-677

Sevigny, Jeff; Ryan, Jillian; Dyck, C H van; Peng, Yahong; Lines, Christopher; Nessly, Michael L.

doi:10.1212/01.wnl.0000335163.88054.e7

Cited by 80 publications

(74 citation statements)

References 23 publications

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“…However, application of the GH secretagogue MK-677, which is a potent inducer of IGF-I secretion, did not show a clinical effect on the disease progression in patients with AD in a randomised trial (Sevigny et al, 2008). More and detailed data is warranted from ongoing trials, which plan to finally evaluate the efficacy of IGF-I variants as potential AD modifying agents.…”

Section: Accepted M Manuscriptmentioning

confidence: 96%

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Skin and brain age together: The role of hormones in the ageing process

Makrantonaki

Schönknecht

Hossini

et al. 2010

Experimental Gerontology

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The importance of the endocrine environment in the initiation of the ageing process has been elucidated in several in vivo an in vitro studies. Changes in endocrine pathways accompany healthy ageing, these include the growth hormone /insulin like growth factor-I axis (somatopause) and that of sexual hormones, namely estradiol (menopause), testosterone (andropause), and dehydroepiandrosterone and its sulphate (adrenopause). The clinical significance of these changes is variable and results in morphological and functional alterations of all organ systems including the skin and the central nervous system. Moreover, the pathogenesis of age-associated diseases such as epithelial skin cancer and neurodegenerative diseases has been partly attributed to the lack of hormones. Several studies have been conducted in an attempt to reverse the ageing process and clinical signs by substitution of the serum hormone levels in older individuals, however the benefits of hormone replacement therapy, if any, are still controversial. On the other hand, recent data suggest that skin is a window to the human organism and represents an adequate model for ageing research, also implying the use of skin samples for evaluating the ageing status of the central nervous system.

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Section: Accepted M Manuscriptmentioning

confidence: 96%

“…(Sevigny et al, 2008) • ZR-75-1 cells (human breast carcinoma cell line) were • Induction of soluble Alzheimer amyloid precursor (Jaffe et al, 1994) A C C E P T E D M A N U S C R I P T…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Skin and brain age together: The role of hormones in the ageing process

Makrantonaki

Schönknecht

Hossini

et al. 2010

Experimental Gerontology

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“…ADLs were measured in 55 trials, using 12 measures. 27,28,33,37,41,45,46,49,51,52,54,55,57,59,61,63,64,66,68,77,78,81,[85][86][87][88][89][90]92,97,104,[106][107][108][110][111][112]114,115,118,119,[121][122][123][124][125]128,134,135,137,138,[142][143][144][145] Biological markers were measured in 51 trials using a variety of nine biological t...…”

Section: Published Trialsmentioning

confidence: 99%

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Webster

Groskreutz

Grinbergs-Saull

et al. 2017

Health Technol Assess

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Background: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. Objectives: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). Data sources: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. Review methods: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. Results: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Limitations: Most of the trials inclu...

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“…In the Protocol 030 trial, post hoc analysis suggested a possible beneficial effect of growth hormone secretagogue on AD progression rate in e4 non-carriers only 13 similar to the result seen with RSG treatment. In the rofecoxib study, however, conversion rate from mild cognitive impairment to AD was increased with rofecoxib treatment regardless of apoE genotype.…”

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confidence: 80%

“…13 Briefly, this was a 12-month randomized, double-blind, placebo-controlled trial which took place between November 2003 and January 2005. Patients were at least 50 years old, met criteria for probable AD, and had a Clinical Dementia Rating of 1 or 2 (mild-to-moderate severity) and a Mini Mental State Exam score between 14 and 26.…”

mentioning

confidence: 99%