Z-Drugs for Sleep Disorders in Alzheimer's Disease

Z-Drugs for the Treatment of Sleep Disorders in Alzheimer's Disease: a Randomized, Triple-blind, Placebo-controlled Study

The purpose of this study is to determine whether Zolpidem and Zoplicone are efective in the treatment of sleep disorders in Alzheimer's disease (AD)

Study Overview

• Status: Completed
• Conditions: Insomnia; Sleep; Alzheimer's Disease; Sleep Disorders
• Intervention / Treatment: Drug: Placebo; Drug: Zolpidem; Drug: Zoplicone

Detailed Description

Sleep disorders (SD) affects 35 to 50 percent of patients with AD. These disorders often make caring for patients at home very difficult. Zolpidem and Zoplicone are prescribed drugs for sleep disorder in AD patients.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Distrito Federal
    • Brasilia, Distrito Federal, Brazil
      • Geriatric Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 55 years of age or older
• Diagnosis of probable Alzheimer's disease (AD) by National Institute of Neurological and Communicative Disorders and Stroke / the Alzheimer's Disease and Related Disorders Association Criteria
• Hachinski Ischemia Scale less than 5
• Mini-Mental State Examination score of 0 to 26
• Actigraph evidence of a mean time immobile of less than 7 hours per night based on at least 7 nights of complete actigraph data collected over a single week
• Four-week history of sleep disorder behaviors, occurring at least once weekly, as reported by the caregiver using the Neuropsychiatric Inventory (NPI) Nighttime Behavior scale
• Sleep disturbance observed was not present before the diagnosis of AD
• Other co-morbidities, especially delirium, depression, chronic pain and medication use may be present, but do not cooperate in the primary symptoms
• Computed tomography or magnetic resonance imaging since the onset of memory problems showing no more than 1 lacunar infract in a nonstrategic area and no clinical events suggestive of stroke or other intracranial disease or normal
• Stable medications for 4 weeks prior to the screening visit
• Having a mobile upper extremity to which to attach an actigraph
• Residing with a responsible spouse, family member, or professional caregiver who is present during the night and would agree to assume the role of the principle caregiver for the 3-week protocol
• Ability to ingest oral medication and participate in all scheduled evaluations

Exclusion Criteria:

• Sleep disturbance associated with an acute illness, delirium or psychiatric disease
• Clinically significant movement disorder, such as akinesia, that would affect actigraphic differentiation of sleep and wakefulness
• Severe agitation
• Unstable medical condition
• Discontinuation of psychotropic or sleep medication within 2 weeks of the screening visit
• Patient unwilling to maintain caffeine abstinence after 2:00pm for the duration of the protocol
• Patient unwilling to comply with the maximum limit of 2 alcoholic drinks per day, and only 1 alcoholic drink after 6:00pm for the duration of the protocolo
• Prior use of zolpidem/zoplicone for the treatment os sleep disturbances
• Caregiver deemed to be unreliable to supervise the wearing of the actigraph, to administer study capsules at the proper time, to maintain the sleep diary, or to bring the patient to the scheduled visits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zolpidem; Study group will receive zolpidem 10mg capsules, 10pm (before bedtime) for 14 nights	Drug: Zolpidem; Zolpidem tablets, 10mg, 10pm (before bedtime) for 14 nights
Experimental: Zoplicone; Study group will receive zoplicone 7.5mg capsules, 10pm (before bedtime) for 14 nights	Drug: Zoplicone; Zoplicone tablets, 7.5mg, 10pm (before bedtime) for 14 nights
Placebo Comparator: Placebo; Study group will receive inactive or inert capsules, which will be used as a comparator, 10pm (before bedtime) for 14 nights	Drug: Placebo; Inactive or inert pill which will be used as a comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nighttime Total Sleep Time	Mean Total Sleep Time (in minutes) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment	Baseline, 14 days follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daytime Total Sleep Time	Daytime Total Sleep Time (in minutes) during the 12h daytime period (8:00am-8:00pm) after 2 weeks under treatment	Baseline, 14 days follow-up
Ratio of daytime to nighttime sleep	Daytime Total Sleep Time / Nighttime Total Sleep Time	Baseline, 14 days follow-up
Nighttime Wake after Sleep Onset	Nighttime Wake after Sleep Onset (in minutes) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment	Baseline, 14 days follow-up
Proportion of sleep time at nighttime	Proportion of sleep time (%) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment	Baseline, 14 days follow-up
Proportion of patients with gain of at least 30 minutes in Total Sleep Time	Proportion of patients with gain of at least 30 minutes in Total Sleep Time after 2 weeks under treatment	Baseline, 14 days follow-up
Differences between sleep efficiency between the two treatments.	Analyze possible differences between sleep efficiency between the two treatments after 2 weeks under treatment	Baseline, 14 days follow-up
Nighttime Number of Awakenings	Change in scores of nighttime number of awakenings from baseline to intervention weeks	Baseline, 14 days follow-up

Collaborators and Investigators

• Sponsor: Brasilia University Hospital
• Investigators: Principal Investigator: Luciana L. Louzada, MD, MsC, Brasilia University - Brasilia's University Hospital - Geriatric Medical Center

Publications and helpful links

General Publications

• Louzada LL, Machado FV, Quintas JL, Ribeiro GA, Silva MV, Mendonca-Silva DL, Goncalves BSB, Nobrega OT, Camargos EF. The efficacy and safety of zolpidem and zopiclone to treat insomnia in Alzheimer's disease: a randomized, triple-blind, placebo-controlled trial. Neuropsychopharmacology. 2022 Jan;47(2):570-579. doi: 10.1038/s41386-021-01191-3. Epub 2021 Oct 11.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: March 5, 2017
• First Submitted That Met QC Criteria: March 5, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 8, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Treatment; Insomnia; Alzheimer Disease; Sleep Disturbances; Z-Drugs
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Neurologic Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Parasomnias; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Agents; Sleep Aids, Pharmaceutical; GABA-A Receptor Agonists; GABA Agonists; Zolpidem
• Other Study ID Numbers: ZOLP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No