Memory Consolidation in Pharmacologically Enhanced Naps

Study Overview
=================
Brief Summary
-----------------
This study will examine whether various drugs affecting sleep cycles can improve different kinds of memory.

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.

Official Title
-----------------
Understanding Memory Consolidation by Studying Pharmacologically Enhanced Naps.

Conditions
-----------------
Sleep

Intervention / Treatment
-----------------
* Drug: zolpidem
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zolpidem first, then placebo<br>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<br>* Participants will receive one dose of 10 mg before each nap.<br>Drug: Placebo<br>* Participants will receive a dose of placebo before each nap.<br>|
| Placebo Comparator: Placebo first, then zolpidem<br>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<br>* Participants will receive one dose of 10 mg before each nap.<br>Drug: Placebo<br>* Participants will receive a dose of placebo before each nap.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nap, Pharmacology, Memory, Visual Learning, Verbal Memory, Motor Learning