Zolpidem CR and Hospitalized Patients With Dementia

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00814502
• Collaborator: Sanofi (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Dementia; Alzheimer Disease; Dementia, Vascular; Sleep Disorders; Circadian Dysregulation	Drug: Zolpidem CR; Drug: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Does Zolpidem CR Treatment Change Clinical Outcomes in Elderly Hospitalized Patients With Dementia- A Pilot Study
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Sleep Efficiency [Post-intervention, up to 3 weeks]

   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.

2. Sleep Minutes [post-intervention, up to 3 weeks]

   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.

Secondary Outcome Measures

1. Measures of Aggression, Psychosis, General Clinical Status, Cognitive Measures, Mood Symptoms [post-intervention, up to 3 weeks]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02144

Sponsors and Collaborators

• Massachusetts General Hospital
• Sanofi

Investigators

• Principal Investigator: Kaloyan S Tanev, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kaloyan Tanev, MD, Neuropsychiatrist, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00814502
• Other Study ID Numbers: 2008-P-001434/1
• First Posted: Dec 25, 2008
• Last Update Posted: May 22, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kaloyan Tanev, MD, Neuropsychiatrist, Massachusetts General Hospital: Alzheimer disease; Dementia, vascular; Actigraphy; Circadian dysregulation; Sleep Disorders; Circadian rhythm
• Additional relevant MeSH terms: Alzheimer Disease; Dementia; Sleep Wake Disorders; Parasomnias; Dementia, Vascular; Chronobiology Disorders; Zolpidem

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from among the patients admitted to the Massachusetts General Psychiatric inpatient service, Blake 11. Inclusion criteria included age between 60-99 years and a clinical diagnosis of Alzheimer's dementia and/or vascular dementia using DSM-IV criteria.
Pre-assignment Detail	3 subjects signed informed consent (IC) but were never randomized, and are not included in the table below. One changed his mind prior to randomization; another had untreated sleep apnea, discovered the day after he signed IC; the IC of a third subject was not received from her health care proxy until after her discharge from the hospital.

Arm/Group Title	Zolpidem CR	Placebo
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects randomized to Zolpidem CR received Zolpidem CR 6.25mg by mouth (1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.	Subjects randomized to Placebo After a 48-hour period of baseline actigraphy and clinical measurements, study subjects randomized to Placebo received Placebo by mouth (also 1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.
Period Title: Overall Study
STARTED	8	9
COMPLETED	7	7
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Zolpidem CR	Placebo	Total
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.	Subjects randomized to Placebo Zolpidem CR placebo: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.	Total of all reporting groups
Overall Participants	8	9	17
Age, Customized (Count of Participants)
Age > = 60	8 100%	9 100%	17 100%
Age < 60	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 37.5%	4 44.4%	7 41.2%
Male	5 62.5%	5 55.6%	10 58.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 50%	5 55.6%	9 52.9%
Unknown or Not Reported	4 50%	4 44.4%	8 47.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 11.1%	1 5.9%
White	7 87.5%	8 88.9%	15 88.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 12.5%	0 0%	1 5.9%
Region of Enrollment (participants) [Number]
United States	8 100%	9 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Sleep Efficiency
Description	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.
Time Frame	Post-intervention, up to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem CR	Placebo
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects took Zolpidem CR 6.25mg by mouth (1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.	Subjects randomized to Placebo After a 48-hour period of baseline actigraphy and clinical measurements, study subjects took Placebo by mouth (also 1 pink tablet) for up to 3 weeks or the end of the subjects' hospital stay.
Measure Participants	8	9
Least Squares Mean (Standard Error) [percentage of sleep (see above)]	75.93 (3.24)	75.30 (3.14)

2. Primary Outcome

Title	Sleep Minutes
Description	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.
Time Frame	post-intervention, up to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem CR	Placebo
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.	Subjects randomized to Placebo Zolpidem CR placebo: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.
Measure Participants	8	9
Least Squares Mean (Standard Error) [sleep minutes]	443.71 (30.11)	422.49 (29.27)

3. Secondary Outcome

Title	Measures of Aggression, Psychosis, General Clinical Status, Cognitive Measures, Mood Symptoms
Description	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
Time Frame	post-intervention, up to 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem CR	Placebo
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.	Subjects randomized to Placebo Zolpidem CR placebo: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.
Measure Participants	8	9
NPI Total Score	18.00 (5.72)	18.64 (5.36)
RAGE Total Score	1.40 (1.31)	5.82 (2.07)
DBRS Total Score	22.64 (0.56)	22.47 (0.58)
MMSE Total Score	24.45 (2.05)	21.57 (1.93)
MADRS Total Score	22.96 (4.75)	22.56 (4.80)

Adverse Events

Time Frame	Overall time frame of adverse events collection - 4 years, 2 months. Per subject time frame of adverse events collection - duration of study participation - variable length, up to 21 days.
Adverse Event Reporting Description	Adverse events were collected by regular investigator assessment, and by medical inpatient chart review of subjects participating in the study.
Arm/Group Title	Zolpidem CR		Placebo
Arm/Group Description	Subjects randomized to Zolpidem CR Zolpidem CR: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.		Subjects randomized to Placebo Zolpidem CR placebo: After a 48-hour period of baseline actigraphy and clinical measurements, study subjects will be 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.
All Cause Mortality
	Zolpidem CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Serious Adverse Events
	Zolpidem CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Zolpidem CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		2/9 (22.2%)
Nervous system disorders
Dizziness	2/8 (25%)		1/9 (11.1%)
Confusion	0/8 (0%)		2/9 (22.2%)
Feeling "foggy" or tired	1/8 (12.5%)	1	0/9 (0%)	0

Limitations/Caveats

Small sample size. We were unable to control for different treatments that our subjects received as inpatients.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.