Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT00156533
• Collaborator: Sanofi-Synthelabo (Industry)
• Enrollment: 20
• Location: 1
• Arms: 4
• Duration (Months): 35.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

We want to assess whether "how and when" one takes sleep medication results in similar or different outcomes with respect to symptom relief. We also want to know whether taking medication for a period of time provides continued benefit once the medication is stopped.

Condition or Disease	Intervention/Treatment	Phase
Insomnia; Primary Insomnia; Psychophysiologic Insomnia	Drug: Zolpidem; Drug: Sugar Pill	Phase 4

Detailed Description

To date, the aggressive treatment (Tx) of chronic insomnia has been evaluated in terms of whether maintenance therapy is possible. While what constitutes maintenance therapy is a matter of debate, there are two studies which show that benzodiazepine receptor agonists (BZRAs) 1) are effective when used intermittently for up to 3 months and 2) may be used on a nightly basis for up to 6 months with no loss of efficacy.

The significance of the present research is two fold. First, it will allow us to compare the two primary strategies used for long term treat of insomnia (nightly dosing vs intermittent dosing). Second, it will allow an evaluation of the possibility that extended treatment, given careful withdrawal from medication, may yield long term clinical gains.

Re: Objective 1: It is widely assumed that intermittent dosing confers increased efficacy. That is, less frequent medication use will extend the duration of time for which the medication is maximally potent. An empirical assessment of this proposition is required. If incorrect, physicians and patients should be encouraged to adopt a more aggressive approach to treatment. If correct, physicians and patients should be encouraged to adopt the intermittent dosing approach to treatment.

Re: Objective 2: It is widely assumed that treatment with sedatives (sleep promoting medications) constitutes only palliative care. An empirical assessment of this proposition is required. If correct, physicians and patients should be encouraged to adopt a more aggressive approach to long term treatment. If incorrect, physicians and patients should be encouraged to adopt an approach to treatment that is not currently a standard of practice: extended treatment with a clear plan to taper medication that is designed to maintain the clinical gains that occurred with medication use.

We propose to evaluate the above issues in a pilot study of 40 subjects with Primary Insomnia where subjects are randomized to one of 4 conditions:

1. QHS dosing with placebo

2. QHS dosing with 10mg of zolpidem

3. Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed)

4. Monitor only condition.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Long Term Treatment With Zolpidem: The Relative Efficacy of Nightly (Quaque Hora Somni [QHS]) & Intermittent Dosing and the Potential for Long Term Clinical Gains After Treatment Discontinuation.
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo QHS dosing with placebo (i.e. nightly dose)	Drug: Sugar Pill
Active Comparator: QHS Zolpidem QHS dosing with 10mg of zolpidem (i.e. nightly dose)	Drug: Zolpidem; 10 mg of Zolpidem; Other Names: Ambien
Experimental: Intermittant Zolpidem Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed	Drug: Zolpidem; 10 mg of Zolpidem; Other Names: Ambien
No Intervention: Control Monitor only condition (no placebo, no drug).

Outcome Measures

Primary Outcome Measures

1. Sleep Latency (SL) [Baseline and Post-treatment (12wks)]

   Number of subjects with any reduction in SL (time to fall asleep in minutes)at post-tx compared to baseline where mean SL = mean of daily values for one week calculated from sleep diary values.

Secondary Outcome Measures

1. Wake After Sleep Onset (WASO) [Baseline and Post-Treatment (12 weeks)]

   Number of subjects with any reduction in WASO at post-tx compared to baseline where mean WASO = mean of daily values for one week calculated from sleep diary values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ages 25 - 55

• a stable sleep/wake schedule with a preferred sleep phase between 10:00 p.m. and 8:00 a.m.

• Patients with Primary Insomnia will meet diagnostic criteria for Psychophysiologic Insomnia according to the International Classification of Sleep Disorders manual (ICSD).

• complaint of disturbed sleep must have the following characteristics: >30 minutes to fall asleep, and/or >30 minutes wake after sleep onset time, a total sleep time of no more than 6.5 hours (or a sleep efficiency of less than 85%), a problem frequency of

4 nights/ week and a problem duration >6 months.

Exclusion Criteria:

• Unstable medical or psychiatric illness

• Use of medication that may cause insomnia or may be reduce the effectiveness of zolpidem (e.g. selective serotonin reuptake inhibitors(SSRI's), steroids, bronchodilators, calcium channel blockers, beta blockers, etc.)

• symptoms suggestive of sleep disorders other than insomnia

• polysomnographic data indicating sleep disorders other than insomnia

• Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence

• inadequate language comprehension

• pregnancy

• first-degree relatives with bipolar disorder or schizophrenia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Rochester Sleep Research Laboratory	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• Sanofi-Synthelabo

Investigators

• Principal Investigator: Michael L Perlis, Ph.D., University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wilfred Pigeon, PhD, Assistant Professor of Psychiatry, University of Rochester
• ClinicalTrials.gov Identifier: NCT00156533
• Other Study ID Numbers: PI Initiated; 11045
• First Posted: Sep 12, 2005
• Last Update Posted: Nov 20, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Wilfred Pigeon, PhD, Assistant Professor of Psychiatry, University of Rochester: Insomnia; Sleep; zolpidem; Ambien; Hypnotics
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Zolpidem

Study Results

Participant Flow

Recruitment Details	Subjects recruited from television and newspaper ads. After a telephone or web based screening, subjects brought into the lab to read the Informed Consent Form (ICF). After the ICF has been signed, an initial medical and psychiatric evaluation completed. If the subjects remain eligible they are required to keep two weeks of sleep diaries.

Arm/Group Title	Placebo	QHS (Nightly) Zolpidem	Intermittant Zolpidem	CTRL
Arm/Group Description	Once nightly dosing (quaque hora somni [QHS])with placebo	Once nightly (QHS) dosing with 10mg of zolpidem	Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed	Monitor only condition.
Period Title: Overall Study
STARTED	5	5	5	5
COMPLETED	3	3	3	3
NOT COMPLETED	2	2	2	2

Baseline Characteristics

Arm/Group Title	Placebo	QHS Zolpidem	Intermittant Zolpidem	CTRL	Total
Arm/Group Description	QHS dosing with placebo	QHS dosing with 10mg of zolpidem	Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed	Monitor only condition.	Total of all reporting groups
Overall Participants	5	5	5	5	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	5 100%	5 100%	20 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 80%	3 60%	3 60%	4 80%	14 70%
Male	1 20%	2 40%	2 40%	1 20%	6 30%

Outcome Measures

1. Primary Outcome

Title	Sleep Latency (SL)
Description	Number of subjects with any reduction in SL (time to fall asleep in minutes)at post-tx compared to baseline where mean SL = mean of daily values for one week calculated from sleep diary values.
Time Frame	Baseline and Post-treatment (12wks)

Outcome Measure Data

Analysis Population Description

Completers Only

Arm/Group Title	Placebo	QHS Zolpidem	Intermittant Zolpidem	CTRL
Arm/Group Description	QHS (i.e., nightly) dosing with placebo	QHS (i.e., nightly) dosing with 10mg of zolpidem	Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed)	Monitor only condition (no placebo and no zolpidem).
Measure Participants	3	3	3	3
Number [participants]	1 20%	2 40%	3 60%	0 0%

2. Secondary Outcome

Title	Wake After Sleep Onset (WASO)
Description	Number of subjects with any reduction in WASO at post-tx compared to baseline where mean WASO = mean of daily values for one week calculated from sleep diary values.
Time Frame	Baseline and Post-Treatment (12 weeks)

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Placebo	QHS Zolpidem	Intermittant Zolpidem	CTRL
Arm/Group Description	QHS (i.e., nightly) dosing with placebo	QHS (i.e., nightly) dosing with 10mg of zolpidem	Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed	Monitor only condition.
Measure Participants	3	3	3	3
Number [participants]	1 20%	2 40%	2 40%	1 20%

Adverse Events

Arm/Group Title	Placebo		QHS Zolpidem		Intermittant Zolpidem		CTRL
Arm/Group Description	QHS dosing with placebo		QHS dosing with 10mg of zolpidem		Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed		Monitor only condition.
All Cause Mortality
	Placebo		QHS Zolpidem		Intermittant Zolpidem		CTRL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		QHS Zolpidem		Intermittant Zolpidem		CTRL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		QHS Zolpidem		Intermittant Zolpidem		CTRL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)

Limitations/Caveats

About 25% of the target sample was obtained. As a result our capacity to detect trends and to calculate effect sizes was greatly diminished. Accordingly, our observations must be very limited in scope.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.