Zolpidem CR and Hospitalized Patients With Dementia

Does Zolpidem CR Treatment Change Clinical Outcomes in Elderly Hospitalized Patients With Dementia- A Pilot Study

The purpose of this research study is to compare the effectiveness of Zolpidem CR to that of placebo in improving sleep efficiency in people with dementia admitted to the hospital because of their symptoms. You can participate in this study if you have dementia of the Alzheimer's type or vascular dementia. This study involves placebo; a placebo is a tablet that looks exactly like Zolpidem CR, the study drug, but contains no active study drug. We will use placebos to see if the study results are due to the study drug or due to other reasons. Zolpidem CR is also called Ambien CR and is widely available by prescription. Zolpidem CR is approved by the U.S. Food and Drug Administration (FDA) for the short-term treatment of insomnia (trouble falling or staying asleep).

Study Overview

• Status: Completed
• Conditions: Dementia; Alzheimer Disease; Dementia, Vascular; Sleep Disorders; Circadian Dysregulation
• Intervention / Treatment: Drug: Zolpidem CR; Drug: Placebo

Detailed Description

Sleep patterns normally change with age. Sleep/wake cycles appear to be compromised in people suffering from dementia. Most research involving sleep in dementia has involved community dwelling or nursing home residents. Relatively little is known about the sleep patterns of patients with dementia who develop acute behavioral and psychiatric symptoms and necessitate hospitalization. The relationship between sleep disturbances in these patients and behavioral/psychiatric symptoms is also insufficiently studied. The current study will examine these two sets of data (sleep/wake cycles and clinical symptoms) in a population of elderly subjects with Dementia of the Alzheimer's type (DAT) or vascular dementia (VD) during their hospitalization period. We will compare the sleep outcome measures (primarily sleep efficiency) and clinical outcome measures in subjects treated with Zolpidem CR or Placebo. We will utilize a double-blind, randomized, placebo-controlled design to test our hypothesis that targeting sleep disturbances in hospitalized elderly subjects with DAT or VD leads to improvement in sleep and clinical outcomes.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 60-99 years
• Clinical diagnosis of Dementia of the Alzheimer's type or Vascular Dementia
• Only subjects with Mini Mental Status Examination scores of greater or equal to 10 will be enrolled.

Exclusion Criteria:

1. Subjects who are too agitated to be able to wear the activity monitors;
2. Subjects who are actively suicidal or homicidal or for whom the clinical treatment team considers participation in the study to be unsuitable;
3. Subjects with untreated primary sleep disorders;
4. Subjects who receive hypnotic medications during their participation in the study; Subjects who received hypnotic medications prior to enrollment may participate in the study if they agree to stop receiving hypnotic medications (with their attending physician's approval);
5. Subjects who are receiving over the counter sleep aids;
6. Subjects who can not commit to abstaining from alcohol use while in the study;
7. Subjects with known anaphylactic reaction or angioedema with Zolpidem CR.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zolpidem CR; Subjects randomized to Zolpidem CR	Drug: Zolpidem CR; After a 48-hour period of baseline actigraphy and clinical measurements, study subjects were randomized to take either Zolpidem CR 6.25mg by mouth (1 pink tablet) or Placebo by mouth (also 1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.; Other Names: Ambien CR
Placebo Comparator: Placebo; Subjects randomized to Placebo	Drug: Placebo; After a 48-hour period of baseline actigraphy and clinical measurements, study subjects were randomized to take either Zolpidem CR 6.25mg by mouth (1 pink tablet) or Placebo by mouth (also 1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Efficiency	Sleep efficiency during the down interval. The down interval signifies the period of time (in minutes) at night when subjects are in bed and trying to sleep. Sleep efficiency is calculated as (100*sleep minutes)/[time interval from sleep onset (as defined by the sleep latency) to sleep offset (the end of the last sleep episode in the Down interval)]. The time period was different for each patient, it was their duration of hospitalization. The first 48 hours patients were not on the study drug, so the reported least squares mean is an estimate of the mean for the subsequent time period where the patients received different therapies. These means are corrected for differences that might have existed during the first 48 hours. The results would be similar to the results attained from considering the mean during the first 48 hours as a baseline covariate in an Analysis of Covariance, but would be more robust to missing data.	Post-intervention, up to 3 weeks
Sleep Minutes	Total sleep minutes during the down period. The down interval signifies the period of time (in minutes) at night when subjects are in bed and trying to sleep. The time period was different for each patient, it was their duration of hospitalization. The first 48 hours patients were not on the study drug, so the reported least squares mean is an estimate of the mean for the subsequent time period where the patients received different therapies. These means are corrected for differences that might have existed during the first 48 hours. The results would be similar to the results attained from considering the mean during the first 48 hours as a baseline covariate in an Analysis of Covariance, but would be more robust to missing data.	post-intervention, up to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of Aggression, Psychosis, General Clinical Status, Cognitive Measures, Mood Symptoms	Rating Scale for Aggressive Behavior in the Elderly (RAGE, 0-61); higher is worse. Disruptive Behavior Rating Scales (DBRS, 0-105); higher is worse. Neuropsychiatric Inventory (NPI, 0-144) - measures 12 different domains of neuropsychiatric symptoms such as delusions, hallucinations, anxiety, depression, apathy, etc.; higher is worse. Montgomery-Asberg Depression Rating Scale (MADRS, 0-90); higher is worse. Mini-mental state examination (MMSE, 0-30); higher is better. The time period was different for each patient, it was their duration of hospitalization. The first 48 hours patients were not on the study drug, so the reported least squares mean is an estimate of the mean for the subsequent time period where the patients received different therapies. These means are corrected for differences that might have existed during the first 48 hours. The results would be similar to the results attained from considering the mean during the firs	post-intervention, up to 3 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Sanofi
• Investigators: Principal Investigator: Kaloyan S Tanev, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 24, 2008
• First Posted (Estimate): December 25, 2008

Study Record Updates

• Last Update Posted (Actual): May 22, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Sleep Disorders; Alzheimer disease; Circadian rhythm; Actigraphy; Dementia, vascular; Circadian dysregulation
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurologic Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Sleep Wake Disorders; Parasomnias; Dementia; Alzheimer Disease; Dementia, Vascular; Chronobiology Disorders; 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: 2008-P-001434/1

Plan for Individual participant data (IPD)

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