Last updated on July 2018

Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease


Brief description of study

Nighttime agitation in persons with Alzheimer's disease causes patient suffering, distresses caregivers, and often results in prescriptions for harmful antipsychotics. Effective treatments are lacking because of limited knowledge of the etiology of nighttime agitation. The investigators propose a clinical trial to better elucidate whether a sleep disorder, restless legs syndrome, may be a mechanism for nighttime agitation, and if treatment with gabapentin enacarbil (Horizant) reduces nighttime agitation, improves sleep, reduces restless legs syndrome behaviors, and reduces antipsychotic medications.

Detailed Study Description

Nighttime agitation and sleep disturbance in persons with dementia (PWD) causes patient suffering, may accelerate cognitive decline, leads to burdened caregivers, and is costly to manage. Pharmacological interventions are primarily antipsychotics and hypnotics. Effectiveness is unconvincing, and these drugs are associated with falls, strokes, and death. There is a lack of tailored, effective, and sustainable treatments for nighttime agitation and sleep disturbance in PWD. The investigators approach to this problem is innovative because, unlike pharmacological interventions in the past, it tailors the intervention to a treatable condition, restless legs syndrome (RLS), which may be causing the nighttime agitation and sleep disturbance. In previous research, the investigators showed that about 24% of PWD have an undiagnosed sleep disorder, RLS; that RLS was associated with nighttime agitation and sleep disturbance in PWD; and the investigators developed and validated an RLS diagnostic and outcome measure suitable for PWD. In order for the investigators' work to significantly impact standards of clinical practice, evidence is needed on whether RLS behaviors cause nighttime agitation, and if treating RLS behaviors reduces or stops nighttime agitation and improves sleep in PWD. The investigators have chosen gabapentin enacarbil (GEn), as the RLS treatment in this research because it is FDA approved for RLS and has a favorable safety profile. The investigators propose an 8-week, double-blind placebo-controlled randomized clinical trial of GEn versus placebo in 136 community-dwelling and long-term care facility residents with nighttime agitation, sleep disturbance, and RLS. The specific aims of this pilot study are to: 1) Determine the effect of GEn, compared to placebo, on nighttime agitation (primary endpoint) in PWD with RLS. The investigators hypothesize that compared to the placebo control group, the treatment group will have fewer nighttime agitation behaviors. 2) Describe the safety profile of GEn compared to placebo in this population. 3) Estimate the effect size of GEn compared to placebo on nighttime sleep and RLS behaviors. The investigators hypothesize that compared to the placebo control group, the treatment group will have better nighttime sleep and fewer RLS behaviors. 4) Explore whether frequency of RLS behaviors is a causal mechanism for nighttime agitation. The investigators hypothesize that frequency of RLS behaviors will mediate the effect of GEn on nighttime agitation behaviors. The results of this study and future definitive trials have the potential to radically shift and drastically improve standards of clinical practice for assessment and treatment of three highly prevalent, often comorbid conditions in PWD: RLS, nighttime agitation, and sleep disturbance. For scientists, the results may provide insight into the mechanism for nighttime agitation and sleep disturbance in PWD and inform future research. For PWD, the findings may result in less nighttime agitation and discomfort from RLS, improved nighttime sleep, and improved sleep may enhance daytime cognitive functioning and quality of life. Application of the findings into the home setting may result in fewer nursing home admissions for PWD and less caregiver burden because the PWD (and their caregivers) can get more sleep.

Clinical Study Identifier: NCT03082755

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