Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults

Abstract

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Development and validation of a short version of the Sarcopenia Quality of Life questionnaire: the SF-SarQoL

“…The number of factors present was evalu-ated with parallel analysis (PA) and Velicer's minimum average partial (MAP) test [35]. (2) The second assumption, local independence, means that there should be no correlation between two items after the effect of the underlying trait is filtered out. In other words, the item responses should be entirely a function of the underlying trait, and not (partly) dependent on a second factor [34].…”

“…The process of ageing is associated with numerous physiological changes. One of these changes is the age-related decrease in muscle mass and function known as sarcopenia, which has received a great deal of interest in the past decade [1,2].…”

Experts’ preferences for sarcopenia outcomes: a discrete-choice experiment from a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) in collaboration with the European Union of Geriatric Medicine Society (EUGMS)

“…To our knowledge, this study provides the first assessment of experts' preferences on sarcopenia outcomes and it revealed some differences between experts and patients. Results of such DCE identifying the most relevant outcomes of sarcopenia could be useful for the choice of primary and secondary endpoints of future interventional studies [12]. As experts and patients assigned different priorities to outcomes of sarcopenia, it is highly important to take both perspectives into account.…”

Cross-Talks between the Cardiovascular Disease-Sarcopenia-Osteoporosis Triad and Magnesium in Humans

“…A growing body of evidence on mitochondrial impairment in sarcopenia has been provided by both animal and human studies, as mitochondrial dysfunction is determinant in age-related loss of skeletal muscle mass and strength [36]. To date, research focuses on the impact of nutritional and pharmacological mitochondria-targeted interventions [36] and on the development of biomarkers, use of drug and non-drug approaches with nutrition and resistance exercise, and high grade clinical trials [37].…”