Wade 2014.
| Methods | RCT, 2 parallel treatment groups | |
| Participants | Number of participants: 73 patients were randomised; 13 of these were in the subpopulation with comorbid insomnia at baseline and hence were relevant to this review. Country: 1 centre in UK; 4 centres in USA Setting: outpatients Diagnosis: AD (diagnostic criteria not specified) Sleep‐related inclusion criteria: a subset of participants had insomnia at baseline, defined as Pittsburgh Sleep Quality Index (PSQI) score ≥ 6 Gender: data available for whole study population only, 36 women, 37 men Age: data available for whole study population only, range 52 to 85 years Severity of dementia: data available for whole study population only, MMSE had to be ≥15 for inclusion Other information: all participants were on stable doses of acetylcholinesterase inhibitor with or without memantine for 2 months prior to recruitment. Patients were instructed to spend 2 hours a day in outdoor daylight. |
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| Interventions | Duration of treatment: 2‐week single‐blind placebo run‐in phase, 24‐week double‐blind randomised treatment phase, 2‐week placebo run‐out phase Treatment group 1: 7 participants from insomnia subpopulation: 2 mg melatonin SR, once daily, 1 to 2 hours before bedtime. Treatment group 2: 6 participants from insomnia subpopulation: placebo |
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| Outcomes |
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| Notes | The study was funded by Neurim Pharmaceuticals. Four of eight authors were paid employees of Neurim Pharmaceuticals. The other four authors have acted as paid consultants to Neurim Pharmaceuticals. The study used the Pittsburgh Sleep Questionnaire (PSQ) as a carer‐reported sleep measure. No evidence was cited for its validity in this context. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Selection for treatment group was determined by a computer‐generated randomization list in a 1:1 ratio using the randomized permuted blocks method." Note: No stratification by baseline sleep score was used to identify insomnia subgroup. |
| Allocation concealment (selection bias) | Unclear risk | No information. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "To prevent bias, matching placebo tablets, which were identical in appearance, taste and odor, were used. The treatment was double‐blinded." |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No information. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | One participant lost from each group. |
| Selective reporting (reporting bias) | High risk | Relation of this report to NCT00940589 and to EUCTR2009‐014388‐38‐GB is uncertain. It seems likely that these all refer to the same study, but we have been unable to get confirmation of this from Neurim Pharmaceuticals. The trial registry entries and this report differ in several respects, including sites and outcome measures. |
| Other bias | High risk | Not clear that insomnia subgroup was defined prospectively. Possible conflict of interest |
Abbreviations AD = Alzheimer's disease ADCS‐ADL = Alzheimer’s Disease Cooperative Study Activities of Daily Living ADAS‐cog = Alzheimer's Disease Assessment Scale ‐ cognitive subscale AEs = adverse events CAS = Caregiver Burden via the Caregiver Activity Survey CGGI = Caregiver Global Impression of sleep CGI = Clinical Global Impression of sleep DSM‐IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition dTST = daytime total sleep time ECG = electrocardiogram h = hour(s) ITT = intention‐to‐treat LOCF = last observation carried forward MMSE = Mini‐Mental State Examination NINCDS‐ADRDA = National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association NPI = Neuropsychiatric Inventory nTST = night‐time total sleep time SDI = Sleep Disorder Inventory SR = slow release VAS = visual analogue scale