Sarcopenia: designing phase IIB trials

Abstract

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength.

Figure 1

An example of strength as a primary outcome