Protocol: Using N-of-1 tests to identify responders to melatonin for sleep disturbance in Parkinson's disease

Abstract

Background 40% of Parkinson's Disease (PD) sufferers experience insomnia, impacting health and quality of life for patients and family members, especially carers. There is little evidence that current treatments are effective. Objectives To determine the effectiveness of melatonin in reducing insomnia in 44 individuals with PD using N-of-1 trials. To aggregate group data to arrive at population estimates of effectiveness (measured by improvements in PDSS-2) and safety (measured by adverse events) of melatonin in improving insomnia in PD. To assess the feasibility of offering N-of-1 trials for insomnia in PD. Methodology Participants will receive either immediate-release melatonin or placebo in random order in 3 paired two-week treatment periods (12 weeks total). Based on their response in a two-week run-in period on 3 mg daily, they will trial either 3 mg or 6 mg. Patients will keep daily sleep diaries and wear a MotionWatch throughout. After the trial patients will discuss their individual report with their doctor, which provides direct feedback about effectiveness and safety of melatonin for them. Statistical methods We will analyse N-of-1 tests 1) individually: effects of melatonin on PDSS-2 and safety will be reported; and 2) aggregated across individual N-of-1 studies, combined using a Bayesian multilevel random effects model, which will account for repeated measures on individuals over time, and will return posterior estimates of overall treatment effect, and effect in each individual. Clinical Trial Registration number ACTRN12617001103358.

Exploring the Potential for Collaborative Use of an App-Based Platform for n-of-1 Trials Among Healthcare Professionals That Treat Patients With Insomnia

“…Punja et al have described a protocol to assess the effectiveness of melatonin in children (ages 6–17) taking medications for ADHD ( 17 ). Nikles et al have described a protocol to assess the effectiveness of melatonin in patients with PD ( 18 ).…”

Exploring the potential for collaborative use of an app-based platform for n-of-1 trials among healthcare professionals that treat patients with insomnia

“…Coxeter et al reported the effectiveness of valerian versus placebo in 24 patients with chronic insomnia [15]. Punja et al have described a protocol to assess the effectiveness of melatonin in children (ages [6][7][8][9][10][11][12][13][14][15][16][17] taking medications for ADHD [16]. Nikles et al have described a protocol to assess the effectiveness of melatonin in patients with PD [17].…”

“…Punja et al have described a protocol to assess the effectiveness of melatonin in children (ages 6-17) taking medications for ADHD [16]. Nikles et al have described a protocol to assess the effectiveness of melatonin in patients with PD [17].…”

Bayesian adaptive N‐of‐1 trials for estimating population and individual treatment effects

“…Such features may seem restrictive in practice, however, N-of-1 trials have been applied widely to inform clinical care for, for example, arthritis, asthma, insomnia, attention deficit hyperactivity disorder, hypertension, sleep disturbance, and fatigue from cancer. [3][4][5][6][7][8] Most notably, N-of-1 trials will typically recruit far fewer patients than randomized controlled trials making them suitable for smaller patient cohorts such as those with rare diseases. 9,10 Furthermore, given individual treatment effects can be estimated, N-of-1 trials are suitable when there is significant variability in response to treatment as seen, for example, in response to the treatment of chronic pain.…”

“…In typical N‐of‐1 clinical trials, treatments do not permanently change the disease or condition, and therefore, once off treatment, the patient will return to their underlying stable state (after a sufficiently long wash‐out period). Such features may seem restrictive in practice, however, N‐of‐1 trials have been applied widely to inform clinical care for, for example, arthritis, asthma, insomnia, attention deficit hyperactivity disorder, hypertension, sleep disturbance, and fatigue from cancer 3‐8 . Most notably, N‐of‐1 trials will typically recruit far fewer patients than randomized controlled trials making them suitable for smaller patient cohorts such as those with rare diseases 9,10 .…”