Nighttime agitation and restless legs syndrome in persons with alzheimer’s disease study protocol for a double-blind, placebo-controlled, randomized trial (Nightrest)

Nighttime agitation is a prevalent symptom in persons with Alzheimer’s disease (AD). Effective treat-ments are absent due to our limited knowledge of its etiology. We hypothesized that restless legs syndrome (RLS), a common neurological sensorimotor disorder of uncomfortable leg sensations that appear at night and interfere with sleep, might be a cause for nighttime agitation in persons with AD. RLS is in-frequently identified in persons with AD because traditional diagnosis is dependent on patients answer-ing complex questions about their symptoms. With a validated observational tool for RLS diagnosis, the Behavioral Indicators Test-Restless Legs, we aim to diagnose RLS and determine the effect of gabapentin enacarbil (GEn) compared to placebo on nighttime agitation, sleep, antipsychotic medications, and the mechanism for these effects. We hypothesize that frequency of RLS behaviors will mediate the relationship between GEn and nighttime agitation. This study is an 8-week, double-blind, placebo-controlled, randomized pilot clinical trial, followed by an 8-week open-label trial, that is being conducted in long-term care settings and private homes. The results of this study may shift, personalize, and improve stan-dards of care for treatment of nighttime agitation; reduce aggression and other nighttime agitation be-haviors; and improve sleep. Targets: Persons with AD with nighttime agitation potentially caused by RLS. Intervention Description: Diagnose RLS and determine the effect of GEn. Mechanisms of Action: The frequency of RLS behaviors will mediate the relationship between GEn and nighttime agitation. Outcomes: Determine the effect of GEn on nighttime agitation, sleep, and antipsychotic medications.