Memory Consolidation in Pharmacologically Enhanced Naps

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00777829
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 33
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study will examine whether various drugs affecting sleep cycles can improve different kinds of memory.

Condition or Disease	Intervention/Treatment	Phase
Sleep	Drug: zolpidem; Drug: Placebo	N/A

Detailed Description

Research provides evidence for strong, specific connections between sleeping and memory. This research shows that sleeping is necessary for certain types of memories to form, certain sleep stages lead to specific types of learning and memory consolidation, and naps are as effective as night-time sleep in these learning and memory processes. Current evidence also indicates that there are different types of memory and that the different types can operate and develop independently. In this study, three different memory types will be examined: perceptual, motor, and declarative memory. Perceptual memory is measured through the ability to recognize discrete stimuli; motor memory is measured through the ability to perform specific, coordinated tasks; and declarative memory is measured through the ability to recite memorized information. Different stages in the sleep cycle correlate with improvements in each of these memory processes. For instance, improvement of perceptual memory tasks is dependent on rapid eye motion (REM) sleep; motor learning is related to sleep stage 2; and declarative memory consolidation is related to short wave sleep (SWS), which includes sleep stages 3 and 4.

New drugs can target specific sleep stages and increase the amount of time people spend in those stages when they sleep. For example, the new prescription drug zolpidem increases time spent in stage 2 during sleep, and the drug sodium oxybate increases time spent in SWS. Compared to sleep impacted by either zolpidem or sodium oxybate, normal sleep has proportionally more time spent in REM. This study will use medications, or their lack, to manipulate how much time is spent in REM, stage 2, and SWS. The study will then examine whether the percentage of sleep spent in different stages affects the learning processes associated with those stages.

Participation in this study will last 6 weeks. At the outset, participants will undergo a 2-hour screening visit that will include a medical history, a physical examination, routine lab tests, urine tests for drugs and pregnancy, an electrocardiogram, and a clinical interview for mental health. Participants will also be asked to complete a series of questionnaires on subjective sleep quality, sleep quantity, and daytime sleepiness.

Participants will complete five study visits, beginning 1 week from screening and separated by 5 to 10 days to allow drug wash-out and recovery from effects of the previous visit. Each study visit will involve an overnight stay in a sleep lab. Participants will arrive at 8 PM, go to bed at 10 PM, and be awakened at 5 AM. Between 6 and 8 AM, they will undergo three different tests, each corresponding to a different type of learning and memory process: perceptual, motor, or declarative. The test will include recognizing a target image, typing a specific finger sequence on a keyboard, and verbally recalling a list of words. Participants will receive one of the study drugs or placebo at 8:30 AM and then be allowed to take a 90-minute nap between 9 and 11 AM. They will receive a different drug, different dosage, or placebo at each study visit. Between 4 and 6 PM, they will be retested on the previous three tests. While sleeping, participants will be outfitted with sensors monitoring muscle activity, eye movements, brain waves, heart and lung functioning, and-on the first night-breathing.

For the entire duration of the study, participants will wear an actigraph, which is a wristwatch-like device that monitors sleep cycles. Participants will also be required to maintain a regular sleep schedule, going to sleep and waking up in the same 2-hour window each day. They will also report on sleep schedule and caffeine, alcohol, and drug use in a daily sleep diary. Caffeine, alcohol, and drug use will be prohibited starting at noon on the day prior to each study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Health Services Research
• Official Title: Understanding Memory Consolidation by Studying Pharmacologically Enhanced Naps.
• Actual Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: zolpidem first, then placebo Participants received one dose of zolpidem for one nap, then had a one week washout period, followed by once dose of placebo for one nap.	Drug: zolpidem; Participants will receive one dose of 10 mg before each nap.; Drug: Placebo; Participants will receive a dose of placebo before each nap.
Placebo Comparator: Placebo first, then zolpidem Participants received one dose of placebo for one nap, then had a one week washout period, followed by once dose of zolpidem for one nap.	Drug: zolpidem; Participants will receive one dose of 10 mg before each nap.; Drug: Placebo; Participants will receive a dose of placebo before each nap.

Outcome Measures

Primary Outcome Measures

1. Pharmacological Enhancement of Specific Sleep Parameters [Two weeks]

   Number of sleep spindles comparing placebo vs active drug. We count spindles in the EEG record.

Secondary Outcome Measures

1. Correlation of Pharmacological Interventions With Sleep-stage-specific Memory Tasks [two weeks]

   improvement on a verbal memory task in active drug. We measured the number of words recalled.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 39 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Speaks English

• Resides in the general San Diego community

• Completed at least 12 years of formal education, because education may affect performance on the cognitive task

Exclusion Criteria:

• No regular sleep-wake schedule, defined as not meeting study criteria or scoring between 31 and 69 on the Horne-Ostberg Morningness-Eveningness Questionnaire

• Presence of a sleep disorder reported or detected on the questionnaires

• Personal or immediate family (i.e., first degree relative) history of diagnosed significant psychopathology

• Personal history of head injury with loss of consciousness for more than 15 minutes or with seizures

• History of substance dependence

• Current use of any psychotropic medications

• Any cardiac, respiratory, or other medical condition that may affect cerebral metabolism

• Noncorrectable vision and audition impairments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD General Clinical Research Center Laboratory for Sleep and Chronobiology (GCRC-LSC)	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Sara C. Mednick, PhD, UCSD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sara C. Mednick, Prinicipal Investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00777829
• Other Study ID Numbers: K01MH080992-01; K01MH080992-01; 071529; DNBBS 7K-TGNB; NCT00773032
• First Posted: Oct 22, 2008
• Last Update Posted: Jul 28, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Sara C. Mednick, Prinicipal Investigator, University of California, San Diego: Nap; Pharmacology; Memory; Visual Learning; Verbal Memory; Motor Learning
• Additional relevant MeSH terms: Zolpidem

Study Results

Participant Flow

Arm/Group Title	Zolpidem First, Then Placebo	Placebo First, Then Zolpidem
Arm/Group Description	Participants received one dose of zolpidem for one nap, then had a one week washout period, followed by once dose of placebo for one nap.	Participants received one dose of placebo for one nap, then had a one week washout period, followed by once dose of zolpidem for one nap.
Period Title: Overall Study
STARTED	15	15
Study Orientation	15	13
COMPLETED	15	13
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	This was a within-subjects design, so all 30 started in the participant flow, but only 28 completed all arms of the study.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	15 50%
Male	15 50%

Outcome Measures

1. Primary Outcome

Title	Pharmacological Enhancement of Specific Sleep Parameters
Description	Number of sleep spindles comparing placebo vs active drug. We count spindles in the EEG record.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem	Placebo
Arm/Group Description	This arm reflects all participants who received the drug (one dose of 10mg before each nap) during the entire course of the study.	This arm reflects all participants who received the placebo (a dose of placebo before each nap) during the entire course of the study.
Measure Participants	28	28
Mean (Standard Deviation) [sleep spindles]	3 (0.5)	1 (0.5)

2. Secondary Outcome

Title	Correlation of Pharmacological Interventions With Sleep-stage-specific Memory Tasks
Description	improvement on a verbal memory task in active drug. We measured the number of words recalled.
Time Frame	two weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem	Placebo
Arm/Group Description	This arm reflects all participants who received the drug (1 dose of 10mg before each nap) during the entire course of the study.	This arm reflects all participants who received the placebo (1 dose of placebo before each nap) during the entire course of the study.
Measure Participants	28	28
Mean (Standard Deviation) [recall of words]	3 (1.0)	1 (0.5)

Adverse Events

Arm/Group Title	Zolpidem		Placebo
Arm/Group Description	This arm reflects all participants who received the drug (1 dose of 10mg before each nap) during the entire course of the study.		This arm reflects all participants who received the placebo (1 dose of placebo before each nap) during the entire course of the study.
All Cause Mortality
	Zolpidem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Zolpidem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Zolpidem		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/28 (60.7%)		0/28 (0%)
General disorders
drowsiness	17/28 (60.7%)		0/28 (0%)
dizziness	12/28 (42.9%)		0/28 (0%)
nausea	4/28 (14.3%)		0/28 (0%)
vomiting	2/28 (7.1%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

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.