Designing a trial to evaluate potential treatments for apathy in dementia: the apathy in dementia methylphenidate trial (ADMET)

Abstract

Background: Research on efficacious treatments for apathy in Alzheimer disease has been hindered by a lack of consensus diagnosis, difficulties in measurement, and studies with small sample sizes.

Methods: In designing the Apathy in Dementia Methylphenidate Trial (ADMET), a trial to evaluate the efficacy and safety of methylphenidate for the treatment of apathy in Alzheimer disease, we encountered the following issues: defining and measuring apathy, distinguishing apathy and depression, determining an appropriate test treatment, selecting relevant secondary outcomes, recruiting participants, and deciding on a suitable method for treatment unmasking. ADMET is a 6-week randomized, double-masked, placebo-controlled multicenter clinical trial with two parallel treatment groups assigned in a 1:1 ratio with randomization stratified by clinical center. The recruitment goal is 60 randomized participants over 2 years. The primary outcomes are change in apathy severity as measured by the Apathy Evaluation Scale and the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change.

Conclusion: The design decisions made for ADMET are important elements to be considered in trials assessing the safety and efficacy of medications for clinically significant apathy in Alzheimer disease.

Figure 1. Change scores for methylphenidate versus placebo in 13 patients

Data from preliminary, randomized, cross-over study of 13 patients on cholinesterase inhibitors. The shaded bars are the mean change (end of treatment minus baseline) such that negative change values indicate improvement, and the lines indicate the standard deviation of the change.