Strategies and Challenges in Clinical Trials Targeting Human Aging

Abstract

Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study.

Keywords: Acarbose; Aging; Clinical trials; Metformin; Rapamycin.

Figure 1.

Schematic of study designs. (A) The natural course of health span is often a gradual decline in function (red dotted line) that results in disability or dependence when a certain threshold is crossed (black dashed line). Interventions that target aging processes and extend health span would delay the occurrence of disability or dependence by slowing this decline (blue solid line). (B) Health span may also be interrupted by an acute stressor, which may push the individual’s function (red dotted line) below the disability/dependence threshold (black dashed line), where the individual may remain after recovery from the stressor. The intervention may enhance the individual’s ability to recover back to independence (blue solid line).