Z-Drugs for Sleep Disorders in Alzheimer's Disease
Primary Purpose
Sleep, Sleep Disorders, Insomnia
Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Zolpidem
Zoplicone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sleep focused on measuring Sleep Disturbances, Alzheimer Disease, Insomnia, Z-Drugs, Treatment
Eligibility Criteria
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
Sites / Locations
- Geriatric Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Zolpidem
Zoplicone
Placebo
Arm Description
Study group will receive zolpidem 10mg capsules, 10pm (before bedtime) for 14 nights
Study group will receive zoplicone 7.5mg capsules, 10pm (before bedtime) for 14 nights
Study group will receive inactive or inert capsules, which will be used as a comparator, 10pm (before bedtime) for 14 nights
Outcomes
Primary Outcome Measures
Nighttime Total Sleep Time
Mean Total Sleep Time (in minutes) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment
Secondary Outcome Measures
Daytime Total Sleep Time
Daytime Total Sleep Time (in minutes) during the 12h daytime period (8:00am-8:00pm) after 2 weeks under treatment
Ratio of daytime to nighttime sleep
Daytime Total Sleep Time / Nighttime Total Sleep Time
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
Proportion of sleep time at nighttime
Proportion of sleep time (%) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment
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
Differences between sleep efficiency between the two treatments.
Analyze possible differences between sleep efficiency between the two treatments after 2 weeks under treatment
Nighttime Number of Awakenings
Change in scores of nighttime number of awakenings from baseline to intervention weeks
Full Information
NCT ID
NCT03075241
First Posted
March 5, 2017
Last Updated
November 8, 2020
Sponsor
Brasilia University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03075241
Brief Title
Z-Drugs for Sleep Disorders in Alzheimer's Disease
Official Title
Z-Drugs for the Treatment of Sleep Disorders in Alzheimer's Disease: a Randomized, Triple-blind, Placebo-controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
October 2016 (Actual)
Primary Completion Date
April 2020 (Actual)
Study Completion Date
April 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brasilia University Hospital
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep, Sleep Disorders, Insomnia, Alzheimer's Disease
Keywords
Sleep Disturbances, Alzheimer Disease, Insomnia, Z-Drugs, Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zolpidem
Arm Type
Experimental
Arm Description
Study group will receive zolpidem 10mg capsules, 10pm (before bedtime) for 14 nights
Arm Title
Zoplicone
Arm Type
Experimental
Arm Description
Study group will receive zoplicone 7.5mg capsules, 10pm (before bedtime) for 14 nights
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Study group will receive inactive or inert capsules, which will be used as a comparator, 10pm (before bedtime) for 14 nights
Intervention Type
Drug
Intervention Name(s)
Zolpidem
Intervention Description
Zolpidem tablets, 10mg, 10pm (before bedtime) for 14 nights
Intervention Type
Drug
Intervention Name(s)
Zoplicone
Intervention Description
Zoplicone tablets, 7.5mg, 10pm (before bedtime) for 14 nights
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inactive or inert pill which will be used as a comparator
Primary Outcome Measure Information:
Title
Nighttime Total Sleep Time
Description
Mean Total Sleep Time (in minutes) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Secondary Outcome Measure Information:
Title
Daytime Total Sleep Time
Description
Daytime Total Sleep Time (in minutes) during the 12h daytime period (8:00am-8:00pm) after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Title
Ratio of daytime to nighttime sleep
Description
Daytime Total Sleep Time / Nighttime Total Sleep Time
Time Frame
Baseline, 14 days follow-up
Title
Nighttime Wake after Sleep Onset
Description
Nighttime Wake after Sleep Onset (in minutes) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Title
Proportion of sleep time at nighttime
Description
Proportion of sleep time (%) during the 12h nocturnal period (8:00pm-8:00am) after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Title
Proportion of patients with gain of at least 30 minutes in Total Sleep Time
Description
Proportion of patients with gain of at least 30 minutes in Total Sleep Time after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Title
Differences between sleep efficiency between the two treatments.
Description
Analyze possible differences between sleep efficiency between the two treatments after 2 weeks under treatment
Time Frame
Baseline, 14 days follow-up
Title
Nighttime Number of Awakenings
Description
Change in scores of nighttime number of awakenings from baseline to intervention weeks
Time Frame
Baseline, 14 days follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luciana L. Louzada, MD, MsC
Organizational Affiliation
Brasilia University - Brasilia's University Hospital - Geriatric Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Geriatric Medical Centre
City
Brasilia
State/Province
Distrito Federal
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34635802
Citation
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.
Results Reference
derived
Learn more about this trial
Z-Drugs for Sleep Disorders in Alzheimer's Disease
We'll reach out to this number within 24 hrs