Clinical trial NCT03657212
Conditions: Aging
Sponsor: University of California, Irvine
Start date: 2018-10-01; Completion date: 2019-01-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this research study is to understand the neural mechanisms underlying long-term memory formation in older adults. Both sleep and memory decrease with age. The investigators are interested in discovering whether these two biological changes are related. This study is specifically focused on understanding what are the critical components of sleep that facilitate memory formation and are they impaired in older adults. The investigators will be using the hypnotic zolpidem, a sleep drug that has been shown to increase a specific aspect of sleep that have been shown to correlate with memory improvement in young adults. The Food and Drug Administration (FDA) have approved zolpidem for use in certain sleep disorders, specifically in the treatment of sleeplessness (i.e., insomnia). In the current study, the investigators will examine whether zolpidem (5mg), compared with placebo, increases memory-related sleep events in older adults and test the impact of these drug-related sleep changes on post-sleep memory recall.

This is a research study because the investigators are using pharmacological interventions to investigate our hypotheses about memory consolidation. The investigators are not studying the efficacy of zolpidem to treat conditions for which the FDA has already approved it.

Detailed description:

Arms: arm 1: The research involves oral administration of zolpidem (ZOL, 5mg) on week one and placebo on week two during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. The order of drug conditions will be randomized and counterbalanced. During the experimental phase, each drug condition will include one day in the sleep lab, two encoding test sessions, and one retrieval test session. Multiple subjects will be in the experimental phase concurrently, and multiple subjects will be tested on each day. arm 2: The research involves oral administration of placebo on week on and zolpidem (ZOL, 5mg) on week two during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. The order of drug conditions will be randomized and counterbalanced. During the experimental phase, each drug condition will include one day in the sleep lab, two encoding test sessions, and one retrieval test session. Multiple subjects will be in the experimental phase concurrently, and multiple subjects will be tested on each day.
Interventions: intervention 1: Zolpidem
Intervention descriptions: intervention 1: The research involves oral administration of zolpidem (ZOL) or placebo during sleep with EEG recording. This study will employ a within-subject, crossover design, in which every subject experiences each of the following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap to be scheduled one week prior to the first experimental day. One condition will be tested per week, with condition order counterbalanced. Each subject will have 2 visits (plus an adaptation nap), each separated by 5-7 days (although this may be extended based on participant availability) to ensure that the drug is completely eliminated from the body. The order of drug conditions will be randomized and counterbalanced.

Protocol documents:
ICF_000.pdf: 
UCI IRB: Biomed Consent – October 2017 
 
 
UNIVERSITY OF CALIFORNIA, IRVINE 
CONSENT TO ACT AS A HUMAN RESEARCH SUBJECT 
 
Enhancing memory consolidation in older adults 
 
 
You are being asked to participate in a research study.  Participation is completely voluntary.  Please 
read the information below and ask questions about anything that you do not understand.  A researcher 
listed below will be available to answer your questions. 
 
 
RESEARCH TEAM 
Lead Researcher 
Sara C. Mednick, PhD 
Department of Cognitive Sciences 
(949)824-4607 
24-Hour Telephone Number/Pager: (858)945-7904 
 
Other Researchers 
Steven C. Cramer, MD – UC Irvine School of Medicine 
Sara J. Stern-Nezer, MD – UC Irvine School of Medicine 
 
 
STUDY LOCATION(S):  
UC Irvine Institute for Clinical and Translational Science (ICTS), Irvine, CA 
UC Irvine Institute for Clinical and Translational Science (ICTS), Orange, CA 
Sleep and Cognition (SaC) lab in the Social Science Research building, room 380 
 
STUDY SPONSOR(S):  
National Institute of Health, Grant #: R01AG046646 
 
 
WHY IS THIS RESEARCH STUDY BEING DONE? 
The purpose of this research study is to understand the neural mechanisms underlying long-term 
memory formation in older adults. Both sleep and memory decrease with age. We are interested in 
discovering whether these two biological changes are related. This study is specifically focused on 
understanding what are the critical components of sleep that facilitate memory formation and are they 
impaired in older adults. We will be using the hypnotic zolpidem, a sleep drug that has been shown to 
increase a specific aspect of sleep that have been shown to correlate with memory improvement in 
young adults. The Food and Drug Administration (FDA) have approved zolpidem for use in certain 
sleep disorders, specifically in the treatment of sleeplessness (i.e., insomnia).  In the current study, we 
will examine whether zolpidem (5mg), compared with placebo, increases memory-related sleep events 
in older adults and test the impact of these drug-related sleep changes on post-sleep memory recall. 
 
This is a research study because we are using pharmacological interventions to investigate our 
hypotheses about memory consolidation. We are not investigating the efficacy of zolpidem to treat 
conditions for which the FDA has already approved it. 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?   
Approximately 60 participants will take part in the research at UCI. 
 
 
AM I ELIGIBLE TO PARTICIPATE IN THIS STUDY? 
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Please note this may not be a complete list of eligibility criteria. We have included a few examples of 
study criteria to help you better understand how your eligibility in the study will be determined; your study 
team will go through the study eligibility criteria with you to verify if you qualify for participation in this 
study. 
  
Inclusion Requirements 
You can participate in this study if you are a healthy, English-speaking, non-smoking adult between the 
ages of 60 to 75 without major medical problems. You must have a regular sleep-wake schedule, defined 
as obtaining 6-9 hours of sleep per night, with a habitual bedtime before 2am and a habitual wake time 
before 10am, and must have experience with Ambien to participate in the study. 
 
Exclusion Requirements  
You cannot participate in this study if you: a) have a sleeping disorder (reported or detected on the 
questionnaires); b) have any personal or immediate family (i.e., first degree relative) history of diagnosed 
mental disorders; c) have any personal history of head injury with loss of consciousness greater than 2 
minutes or seizures; d) have a history of substance dependence; e) currently use any medications that 
could affect sleep and/or thought processes; f) have any cardiac, respiratory or other medical condition 
which may affect cerebral metabolism; g) have dementia i) have non-correctable vision and hearing 
impairments, due to the nature of the stimulus and its presentation, will also be excluded. 
 
 
HOW LONG WILL THE STUDY GO ON? 
You will be involved in this study for about three weeks, although this time frame may be extended for 
scheduling purposes. Your involvement will include the following: in-person interview (1 hour), orientation 
(4 hours), medical history and physical appointment (30 mins), and two nap experimental visits (6:30am-
8pm, total: 13.5 hours/visit).  
 
The study will consist of two nap visits with at least one week in-between visits. The timing of each visit 
will be from 6:30am to 8pm. During both visits, you will complete cognitive testing, 
questionnaires/surveys, and be asked to take a nap. Before each nap, you will be given a pill (either 
Zolpidem or Placebo). After the nap, subjects will continue to stay in the lab to complete further cognitive 
testing and will be supervised and checked for any side effects. 
 
WHAT PROCEDURES ARE INVOLVED WITH THIS STUDY? 
Before you can participate in the main part of the study... 
You will need to have “screening” exams, tests or procedures.  The screening process helps the 
researchers decide if you meet the study requirements listed below.  The screening procedures include: 
 
In-person interview 
You will meet with a research staff for approximately 1 hour. During this time, you will be 
asked about medical or psychiatric conditions you may have, family history of medical or 
psychiatric conditions and your use of prescription and recreational drugs, alcohol, coffee, 
and cigarettes. Additionally, you will be told about all study procedures.  
 
Orientation 
During this appointment, you will be given questionnaires about your sleep-wake habits, 
mood and psychological status, and history of psychiatric symptoms. If any part of this 
process makes you uncomfortable, you are not obligated to answer and may choose to skip 
any question. In addition, you will be expected to inform the investigators of anything that 
occurs during the study that may affect your ability to fully participate in the study, including 
starting or stopping any prescription or over-the-counter medications. Your results will only be 
shared with authorized research personnel to determine eligibility for this study and not for 
other purposes. Afterwards you will complete four tests that measure cognitive abilities that 
include: 
o Digit span forward: You will be presented with a list of items and will be asked to 
repeat them in the same order. Items may include words, numbers or letters.  
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o Digit span backward: You will be presented with a list of items and will be asked to 
repeat them in reverse order. Items may include words, numbers or letters. 
o Stroop task: In this task, you will be presented with the name of a color that is printed 
in a color different from the name and will be asked to name the color. 
o Symbol digit task: This task deals with viewing a list of digit-symbol pairs followed by a 
list of digits. You will then be asked to type of the corresponding symbol under each 
digit as fast as possible. 
You will then be hooked up to an EEG cap and be given an opportunity to nap for two-hours, 
which is monitored. 
 
Medical history and physical appointment 
If you remain eligible after the initial screening interview, you will be scheduled for a medical 
history and physical appointment at the UCI Institute for Clinical and Translational Science 
(ICTS). During this interview, you will also be asked to provide a urine specimen sample. This 
sample will be used for a toxicology screen to ensure you have not engaged in recreational 
drug use. Prior to leaving the medical appointment, you will be loaned an actigraph, an 
activity monitor the size of a watch that measures movement, that needs to worn for one 
week prior to each test day. You will also be asked to maintain a regular sleep-wake schedule 
for one week prior to each test day. This means you will pick a two-hour window at night and 
always go to bed during that window and a two-hour window in the morning and always wake 
up during that window. You must follow this schedule 7 days a week, even on weekends. 
During the period when you are maintaining a regular sleep-wake schedule, you will be asked 
to log your sleep-wake schedule, caffeine, alcohol, and drug use with a daily Sleep Diary. You 
will also be asked to refrain from caffeine, alcohol, and any medications not approved by the 
study staff starting 48 hours prior to each test day. The night before each study day, you will 
be required to spend 8 hours time-in-bed from 10pm-6am, All of this is to assure that you 
have obtained an adequate amount of sleep prior to the study and that you have not 
consumed any substance that interferes with your sleep. 
During the main part of the study... 
If the screening exams, tests and/or procedures show that you can continue to be in the study, and you 
choose to take part, then you will have the following procedures and tests done. The main study tests 
and procedures include:  
 
 
Study Day Timeline  
o Test Session 1 - You will report to the lab at 6:30am and complete two cognitive tasks, 
word pair associates task and finger tapping task, starting at 7am. During the word pair 
associates task, you will be presented with word pairs and asked to remember them as 
you will be tested on them later. As for the finger tapping task, you will be shown a string 
of five digits and be asked to type the string of letter as quickly and as accurately as 
possible for 30 seconds. Each of these tasks take about 30 minutes to complete. 
o EEG Cap Setup - After completing these tasks, electrodes will be attached to your scalp 
and body using a conductive paste. We will use rubbing alcohol to clean your skin/scalp 
and remove any excess dirt, oil or makeup. Prior to attaching the electrodes, we will use 
an exfoliating gel and cotton swab to lightly scrub your skin/scalp to remove any dead skin 
cells. 
o Drug Administration - At 9am, you will be provided a snack. At 9:30am, you will be 
administered one of two possible drug treatments (i.e. 5mg zolpidem, or placebo (a pill 
that looks like the investigational drug but it includes no active ingredients). You will 
always be given a pill administered in a double-blind fashion, meaning that neither you nor 
the researcher(s) conducting the study will know which treatment you are receiving - only 
the research pharmacists know which treatment you are receiving. 
o Nap - Following drug administration, you will be asked to take a nap for 2 hours (from 
10am-12pm) where your sleep will be monitored with routine clinical polysomnographic 
procedures (i.e., a sleep study). We will monitor you the entire time you are in the lab 
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(including monitoring vital signs after the drug ingestion) and will ask you about possible 
drug effects and side-effects at several time points after you take the pill. 
o Break - During your down-time in the lab you will be able to watch TV, listen to music, 
read, eat snacks, etc. but will not be able to leave the lab, take any additional naps, or 
consume caffeine or alcohol. Lunch will be served during your down-time and you will be 
offered an opportunity to stretch your legs, accompanied by a team member. 
o Test Session 2 -  
o At 7pm, you will have a second test session in which you will do different versions of the 
tasks you learned earlier that day. Once testing is completed, research personnel will 
complete a side effects mobility test to ensure that you are well to leave the lab. If you 
experience any adverse events or do not pass the mobility test, you will remain in the lab 
until symptom free. 
 
 
Transportation: During visit days, you will not be allowed to drive or operate a vehicle. You will 
need to be dropped off and picked up by a friend or family member at the beginning and end of 
your visit day. 
 
 
Surveys/Questionnaires – Throughout the study day, you will complete a variety of 
questionnaires to evaluate sleepiness, sleep quality, and mood. 
 
 
Study Equipment: You will be loaned an actigraph device to wear for one week prior to each test 
day. Instructions for caring for the actigraph are listed below: 
- 
Remove the actigraph only when in water (e.g., showering, swimming, etc.), if playing a high 
impact sport (e.g., football), or if any risk of damage. Put watch back on immediately after 
such an instance. 
- 
Any time you remove the actigraph, record the interval that the watch was off and why in your 
sleep diary. 
- 
Although the actigraph is not an extraordinarily delicate instrument, it must still be handled 
with care. Do not strike it against anything rigid and do not drop it.  
- 
You will sign for the particular actigraph issued to you (on a separate form). It is a valuable 
piece of instrumentation, and you will be responsible for its safe return. 
- 
While wearing the actigraph, carry on in your normal daily activities. You will quickly adjust 
and will soon forget about it during day-to-day activities. 
- 
It is extremely important that you wear the watch at night. 
 
 
WHAT ARE THE POSSIBLE SIDE EFFECTS OR RISKS RELATED TO THE STUDY? 
You may have side effects while on the study.  Everyone taking part in the study will be watched carefully 
for any side effects.  However, researchers don't know all the side effects that may happen.  Side effects 
may be mild or very serious.  The researchers may give you medicines to help lessen side effects.  Many 
side effects go away soon after you stop taking the drug. In some cases, side effects can be serious, 
long lasting, or may never go away. 
You should talk to the research team about any side effects you experience while taking part in the 
study. 
Risks and side effects related to Ambien include those which are: 
Likely 
 
Drowsiness 
 
Dizziness 
 
Diarrhea 
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 
Grogginess or feeling as if you have been drugged 
Rare but serious 
 
Getting out of bed while not being fully awake and do an activity that you do not know you are 
doing. After taking AMBIEN, you may get up out of bed while not being fully awake and do an 
activity that you do not know you are doing. The next morning, you may not remember that you 
did anything during the night. You have a higher chance for doing these activities if you drink 
alcohol or take other medicines that make you sleepy with AMBIEN. Reported activities include: 
driving a car ("sleep-driving"), making and eating food, talking on the phone, having sex, and 
sleep-walking 
 
Abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than 
normal, confusion, agitation hallucinations, worsening of depression, and suicidal thoughts or 
actions. Ambien may cause serious effects, including: 
 
Memory loss 
 
Anxiety 
 
Severe allergic reactions. Symptoms include swelling of the tongue or throat, and trouble 
breathing. Get emergency medical help if you get these symptoms after taking Ambien.  
 
Falls, which may lead to severe injuries. 
Risks and side effects related to actigraphy devices include those which are: 
 Likely 
 
Discomfort from wearing the actigraph device if you are not used to wearing a wrist-watch.  
Risks and side effects related to the EEG-equipment include those which are: 
Likely 
 
Discomfort from wearing the electrodes 
 
Feel skin irritation caused by the electrode cream and skin exfoliating process 
Risks and side effects related to the procedures include those which are: 
Likely 
 
Discomfort from refraining from sleeping outside of the designated sleep periods during the 
experiment visits. 
 
Discomfort from refraining to consume caffeine of any kind 48 hours before your test day and 
until you are done with the testing procedure that day.  
Placebo: During this study there is a 50% chance that you will receive a placebo. This could lengthen 
the amount of time before you receive a treatment that may be effective. During this time you may 
experience worsening of your condition. The researchers will carefully monitor your condition. If your 
symptoms worsen and make you uncomfortable, you can withdraw from the study. 
 
Confidentiality: There may be a risk of breach of confidentiality during this study.  
Psychological discomforts: Some of the procedures may cause embarrassment or anxiety, or the 
questions the researchers ask you may be upsetting or make you uncomfortable.  If you do not wish to 
answer a question, you can skip it and go to the next question.  If you do not wish to participate you can 
stop. 
 
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Unknown risks: There may be risks related to the research that we don't know about yet.  However, you 
will be informed of any additional risks to which you may be exposed, and any changes that are made to 
the study, as a result of any newly-identified risks. 
 
Reproductive Risks: You should not get pregnant while in this study as it is not known if the drug used 
in this study could harm an unborn baby. Check with the researchers about what types of birth control, or 
pregnancy prevention, to use while in this study. You should also not breastfeed a baby while in this 
study, for the same reason.  
 
ARE THERE BENEFITS TO PARTICIPATING IN THIS STUDY? 
Participant Benefits 
You will not directly benefit from participation in this study. 
 
Benefits to Others or Society 
Other people may receive the following benefits from the information gathered from this study: The 
investigators may learn more about how sleep affects memory. This may prove important in leading to 
treatments in a wide range of disorders as well as enhancement of normal cognition.  
 
 
WHAT OTHER CHOICES DO I HAVE IF I DON’T WANT TO PARTICIPATE?  
There are no alternative treatments or procedures available.  The only alternative is not to participate in 
this study. 
 
 
WILL I BE PAID FOR TAKING PART IN THIS STUDY?  
 
Compensation 
You will receive $300 in the form of cash for your participation in this study. You will receive your 
compensation upon completion of the study. Compensation is broken down as follows: $100 for each of 
the two nap experimental visits, $50 for the adaptation nap, and a $50 bonus for completing the study. If 
you withdraw from the study before completion, the payment will be prorated based on the portion of the 
study you completed. You will not be compensated for only completing the initial interview or the medical 
examination.   
 
 
Reimbursement  
You will be reimbursed for costs of transportation. 
 
WHAT ARE THE COSTS OF TAKING PART IN THIS STUDY?  
 
There is no cost to you for participation in this study. However, there may be out-of-pocket expenses 
such as parking and transportation fees. 
 
 
WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THIS STUDY?  
It is important that you promptly tell the researchers if you believe that you have been injured because of 
taking part in this study.  You can tell the researcher in person or call him/her at the number listed at the 
top of this form. 
 
If you are injured as a result of being in this study, UCI will provide necessary medical treatment. The 
costs of the treatment may be covered by the University of California or the study sponsor, the National 
Institute of Health, or billed to you or your insurer just like other medical costs, depending on a number of 
factors. The University and the study sponsor do not normally provide any other form of compensation 
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for injury.  For more information about this, you may call UCI Human Research Protections (949) 824-
6068 or (949) 824-2125 or by e-mail at IRB@research.uci.edu 
 
 
WHAT HAPPENS IF I WANT TO STOP TAKING PART IN THIS STUDY?  
You are free to withdraw from this study at any time. If you decide to withdraw from this study, you 
should notify the research team immediately. The research team may also end your participation in 
this study if you do not follow instructions, miss scheduled visits, the study sponsor decides to stop the 
study or your safety and welfare are at risk. 
 
If you experience any of the side effects listed above, if your health worsens, or if you are injured during 
the research, you may need to be withdrawn from the study, even if you would like to continue.  The 
research team will make this decision and let you know if it is not possible for you to continue.  The 
decision may be made to protect your safety and welfare, or because the research plan does not allow 
people who develop certain conditions to continue to participate.  
 
If you withdraw or are removed from the study, the researcher may ask you to return all study-related 
equipment, such as the actigraph wrist monitor.  
 
If you elect to withdraw or are withdrawn from this research study, you may choose to terminate the 
continued use or disclosure of your protected health information (PHI) for research purposes. The 
request to end the use or disclosure of your PHI should be made in writing. 
 
HOW WILL INFORMATION ABOUT ME AND MY PARTICIPATION BE KEPT? 
Subject Identifiable Data  
 
No identifiable information will be collected about you except for your contact information if you agree to 
allow the investigators to retain this information. 
 
 
Data Storage  
 
Research data will be maintained in paper format in a secure location at UCI. Only authorized individuals 
will have access to it.   
 
 
Research data will be stored electronically on a secure computer in an encrypted file with password 
protection. 
 
Data Retention 
 
Investigators will keep the study data for 6 years as required by for studies that include identifiable 
information per HIPAA regulations  
 
WHO WILL HAVE ACCESS TO MY STUDY DATA? 
The research team, authorized UCI personnel, the National Institute of Health, and regulatory entities 
such as the Food and Drug Administration (FDA) and the Office of Human Research Protections 
(OHRP), may have access to your study records to protect your safety and welfare.   
 
Any information derived from this research project that personally identifies you will not be released or 
disclosed by these entities without your separate written consent, except as specifically required by law.  
Research records provided to authorized, non-UCI entities will not contain identifiable information about 
you.  Publications and/or presentations resulting from this study will not include identifiable information 
about you.   
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While the research team will make every effort to keep your personal information confidential, it is 
possible that an unauthorized person might see it.  We cannot guarantee total privacy. 
 
ClinicalTrials.gov is a Web site that provides information about clinical trials.  A description of this clinical 
trial will be available on http://www.clinicaltrials.gov/, as required by U.S. Law.  This Web site will not 
include information that can identify you.  At most, the Web site will include a summary of the results. 
You can search this Web site at any time. 
 
Certificate of Confidentiality  
 
To help us protect your privacy, we are in the process of obtaining a Certificate of Confidentiality. With 
this Certificate, researchers cannot be forced to disclose information that may identify you, even by a 
court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings. The Certificate also prohibits the researcher from providing to any other person not 
connected with the research, your name or any information, document, or biospecimen that contains 
identifiable, sensitive information about you that was collected or created for the research. There are 
exceptions – and they are noted below. 
 
The Certificate of Confidentiality does not prevent researchers from voluntarily disclosing information that 
would identify you as a participant in the research project as required by Federal, State or local laws, and 
with your consent, as necessary, for your medical treatment. This includes the disclosure of information 
that must be released to meet the requirements of the Food and Drug Administration (FDA). No voluntary 
disclosures will be made. 
 
A Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing 
information about yourself or your involvement in this research. If an insurer, employer, or other person 
obtains your written consent to receive research information, the researchers may not use the Certificate 
to withhold the information. 
 
ARE THERE OTHER ISSUES TO CONSIDER IN DECIDING WHETHER TO PARTICIPATE IN THIS 
STUDY?  
 
Use of Specimens  
Any specimens (e.g., urine) obtained for routine labs will be discarded or destroyed once they have been 
used for the purposes described in this consent. 
 
 
Investigator Financial Conflict of Interest  
 
No one on the study team has a disclosable financial interest related to this research project. 
 
 
 
UCI researchers may contact me in the future to ask me to take part in other research studies. 
 
 
YES 
 
NO 
 
 
 
WHO CAN ANSWER MY QUESTIONS ABOUT THE STUDY? 
If you have any comments, concerns, or questions regarding the conduct of this research, please contact 
the research team listed at the top of this form. 
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A 24-hour number is also listed on the top of this form to report any health concerns or unanticipated 
problems you may experience after normal hours or on weekends. 
 
If you wish to ask questions about the study or your rights as a research participant to someone other 
than the researchers or if you wish to voice any suggestions, problems or concerns you may have about 
the study, please contact UCI’s Office of Research by phone, (949) 824-6068 or (949) 824-2125, by e-
mail at IRB@research.uci.edu or at 141 Innovation Drive, Suite 250, Irvine, CA 92697.  
 
What is an IRB?  An Institutional Review Board (IRB) is a committee made up of scientists and non-
scientists.  The IRB’s role is to protect the rights and welfare of human subjects involved in 
research.  The IRB also assures that the research complies with applicable regulations, laws, and 
institutional policies.  
 
 
 
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HOW DO I AGREE TO PARTICIPATE IN THIS STUDY?  
You should not sign and date this consent form until all of your questions about this study have been 
answered by a member of the research team listed at the top of this form. You will be given a copy of this 
signed and dated consent form, and the attached “Experimental Subject’s Bill of Rights” to keep. 
Participation in this study is voluntary.  You may refuse to answer any question or discontinue your 
involvement at any time without penalty or loss of benefits to which you might otherwise be entitled.  
Your decision will not affect your future relationship with UCI or your quality of care at the UCI Medical 
Center.   
 
If, during the course of this study, significant new information becomes available that may relate to your 
willingness to continue to participate, this information will be provided to you by the research team listed 
at the top of the form. 
 
Your signature below indicates you have read the information in this consent form and have had a 
chance to ask any questions you have about this study.   
 
Note: If the research described in this form involves your protected health information (PHI), you 
will be asked to sign separate UC HIPAA Research Authorization form for the use of your PHI.  
 
I agree to participate in the study.  
 
___________________________________________________  
__________________ 
 Subject Signature  
 
 
 
 
 
 
Date 
 
___________________________________________________ 
 Printed Name of Subject   
 
 
 
 
___________________________________________________  
__________________ 
Signature of Person Obtaining Informed Consent 
 
 
Date 
(Individual must be listed on Page 1 of this consent) 
 
___________________________________________________  
 Printed Name of Person Obtaining Informed Consent  
 
 
 
 
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A witness signature is required on this consent form only if: (Researchers: check which one 
applies) 
 
Consent is obtained from the subject via the Short Form process, as approved by the IRB. 
The subject has decision-making capacity, but cannot read, write, talk or is blind.  
The subject’s guardian/legally authorized representative (LAR) cannot read, write, talk or is blind. 
The IRB specifically mandated a witness signature for this study (e.g., high risk and/or invasive  
     research procedures). 
 
Note: The witness must be impartial (i.e. not a member of the subject’s family, not a member of the study 
team).   
 
For the witness:  
I confirm that the information in this consent form was accurately explained to and understood by the 
subject or legally authorized representative and that informed consent was given freely. 
 
 
___________________________________________________ __________________ 
Witness Signature 
 
 
 
 
 
 
    
 Date 
 
___________________________________________________  
Printed Name of Witness 
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UCI IRB: Biomed Consent – October 2017 
 
UNIVERSITY OF CALIFORNIA, IRVINE 
Experimental Subject's Bill of Rights 
 
The rights listed below are the right of every individual asked to participate in a research study. 
You have the right:  
 
1. To be told about the nature and purpose of the study.  
 
2. To be told about the procedures to be followed in the research study, and whether any of the 
drugs, devices, or procedures is different from what would be used in standard practice.  
 
3. To receive a description of any side effects, discomforts, or risks that you can reasonably expect 
to occur during the study.  
 
4. To be told of any benefits that you may reasonably expect from the participation in the study, if 
applicable.  
 
5. To receive a description of any alternative procedures, drugs, or devices that might be helpful, 
and their risks and benefits compared to the proposed procedures, drugs or devices.  
 
6. To be told of what sort of medical treatment, if any, will be available if any complications should 
arise.  
 
7. To be given a chance to ask any questions concerning the research study both before agreeing 
to participate and at any time during the course of the study.  
 
8. To refuse to participate in the research study. Participation is voluntary. You may refuse to 
answer any question or discontinue your involvement at any time without penalty or loss of 
benefits to which you might otherwise be entitled.  Your decision will not affect your right to 
receive the care you would receive if you were not in the experiment.   
 
9. To receive a copy of the signed and dated written consent form and a copy of this form.  
 
10. To be given the opportunity to freely decide whether or not to consent to the research study 
without any force, coercion, or undue influence.  
------------------------------------------------------- 
 
If you have any concerns or questions regarding the research study you should contact the research 
team listed at the top of the consent form. 
 
If you are unable to reach a member of the research team and have general questions, or you have 
concerns or complaints about the research study, research team, or questions about your rights as a 
research subject, please contact the UCI’s Human Research Protections unit in the Office of Research 
by calling (949) 824-6068 or (949) 824-2125 Monday – Friday, 8 am – 5 pm; or by e-mail at 
IRB@research.uci.edu; or by writing us at 141 Innovation Drive, Suite 250, Irvine, CA 92697. 
 
 
 
 
  
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SAP_003.pdf: 
Cover Letter 
Title: Enhancing Memory Consolidation in Older Adults 
NCT: 03657212 
Date: Aug 3, 2018 
 
 
 


Aim 1 Expected Results: Determine the effect of pharmacological intervention during 
sleep on memory performance.  
Studies 1-4 will address Aim 1.  
Study 1: The effect of pharmacologically modulating sleep spindles on declarative 
associative verbal memory.  
We hypothesize that declarative associative verbal memory performance will be increased 
with ZOL in a dose-dependent manner and decreased with SO, compared with placebo. In 
addition, we predict that sleep spindles will be correlated with verbal memory performance 
in all four drug conditions and placebo. Furthermore, the ZOL condition will show absolute 
increases in spindle density compared to placebo. These results would be consistent with 
our hypothesis that sleep spindles are associated with declarative memory.  
Study 2: The effect of pharmacologically modulating sleep spindles on emotional 
memory and emotional arousal.  
We hypothesize that ZOL will show dose-dependent increases in memory for negative and 
high arousal emotional memo- ries, compared with neutral, positive and low arousal 
memories, and compared with placebo. We also hypothesize that SO will decrease 
memory for negative valence and high arousal memories compared with placebo. In 
addition, we hypothesize that spindles will correlate with negative and high arousal 
emotional memories in all five drug conditions, whereas REM sleep will be correlated with 
emotional arousal, consistent with our hypothesis that spindles increase consolidation of 
emo- tional memories, and REM sleep increases processing of emotional arousal (Baran et 
al. 2012).  
Study 3: The effect of pharmacologically modulating sleep spindles on motor memory. 
We hypothesize that there will be no changes in motor learning with either ZOL (increased 
spindle density) or SO (decreased spindle density). How- ever, similar to previous results, 
we predict a positive correlation between spindle density and motor learning in all four 
drug conditions and placebo. This pattern of results would suggest that previous findings of 
correlations between spindles and motor learning are a marker of some as of yet 
unexplained factor, and would increase the specificity of our understand- ing of the role of 
spindles in declarative and non-declarative memory.  
Study 4: The effect of pharmacologically modulating sleep spindles on perceptual 
learning. We hypothesize that ZOL will show dose-dependent decreases in perceptual 
learning compared with placebo and SO. We also predict a positive correlation between 
REM sleep and perceptual learning, and a negative correlation between spindle density 
and perceptual learning in all five conditions. The results will be a strong negative control 
for the role of sleep spindles in declarative and non-declarative memory.  
Aim 2 Expected Results: Determine the effect of pharmacological intervention during 
sleep on memory in older adults.  
Study 5: The effect of pharmacologically modulating sleep spindles on memory in 
older adults. We hypothesize that older adults will show a dose-dependent increase in 
declarative associative verbal memory compared with placebo. In addition, we hypothesize 
that spindle density will increase in a dose-dependent manner, compared with placebo, 
and that performance will be correlated with spindle density.  


Aim 3 Expected Results: Characterize the physiological effects of pharmacological 
intervention on sleep spindles. We hypothesize that sleep will be modulated similarly 
across Studies 1-4. In the experimental nap, we will see a dose-dependent increase in 
sleep spindle density in ZOL, whereas SO will significantly decrease spindle density, 
compared with placebo. We predict that spindle density will be modulated equally for fast 
and slow frequency spindles, and no differences in spindle amplitude, frequency, or 
duration between drug conditions. However, we predict that declarative verbal and 
emotional memory and motor learning will be correlated with the density of fast frequency 
spindles, but not slow frequency spindles. That is, ZOL will increase the amount of 
normally occurring fast and slow spindles, not affect spindle morphology, and only fast 
spindles will correlate with performance. We will examine spindles in Stage Two and SWS 
separately, and NREM (Stage Two + SWS) sleep combined. We expect Stage Two spindles 
and sigma power to be topographically dominant over the central electrodes and that 
spindles and sigma power in deeper NREM sleep will be concentrated in frontal electrode 
sites. As a negative control for spindles, we will examine slow oscillations and expect no 
differences across drug conditions. For sleep stages, we expect that there will be increased 
SWS in the ZOL and SO drug conditions compared with placebo. Furthermore, we predict 
dose-dependent decreases in REM sleep with ZOL, compared with SO and placebo. Both 
drug conditions will increase sleep efficiency by decreasing wake after sleep onset and 
sleep latency, compared with placebo. No differences between conditions in Stage 1, 
Stage Two sleep, or Total Sleep Time (which will be held constant) are predicted.  
In the experimental night (9-10 hours post-drug administration), we hypothesize that there 
will be no differences across drug conditions in spindle density, amplitude, or frequency, 
either in slow or fast frequency spindles. We also hypothesize that SWS will not differ 
across conditions due to a prior study that alternated nights of sleep with ZOL and placebo 
and reported no carry over effects of the drug on NREM sleep (Parrino et al. 2008). The 
study, however, did show increased total sleep time on the placebo night, which we also 
predict for our experimental drug nights, compared with placebo.  
In Study 5, we hypothesize that older adults will show a dose-dependent increase in sleep 
spindle density with ZOL, and increased frequency of frontal spindles (i.e. faster spindles), 
compared with placebo. Furthermore, the density of fast spindles at frontal sites will 
correlate with memory improvement in ZOL conditions.  
 

Prot_001.pdf: 
 
 
 
 
 
Institutional Review Board 
Human Research Protections 
Protocol Narrative ~ Expedited/Full Committee 
Biomedical/Clinical Research  
Version 2017 
Upload this completed narrative and any supplemental documentation 
to the IRB Application.   
IRB USE ONLY – 
HS#: 2018-4179 
Lead Researcher Name:  Sara C. Mednick 
Study Title:  Enhancing memory consolidation in older adults 
 
CLINICAL TRIAL MASTER PROTOCOL AND INVESTIGATIONAL BROCHURE INFORMATION * 
 
 
 
Master Protocol 
Investigator 
Brochure: 
<Specify 
Drug/Device> 
Investigator 
Brochure: 
<Specify 
Drug/Device> 
Sponsor 
Consent 
Form 
Template(s) 
Version #: 
 
 
 
 
Version Date: 
 
 
 
 
[ x ] This study is investigator-authored (investigator developed the study and is conducting the study 
at UCI and/or with other non-UCI sites). 
* Add columns as applicable 
 
NON-TECHNICAL SUMMARY   
 
Provide a brief non-technical summary or synopsis of the study that can be understood by IRB members 
with varied research backgrounds, including non-scientists and non-affiliated members.   
The purpose of this research study is to understand the neural mechanisms underlying long-term 
memory formation in older adults. Both sleep and memory decrease with age. We are interested in 
discovering whether these two biological changes are related. This study is specifically focused on 
understanding what are the critical components of sleep that facilitate memory formation and are they 
impaired in older adults. We will be using the hypnotic zolpidem, a sleep drug that has been shown to 
increase a specific aspect of sleep that have been shown to correlate with memory improvement in 
young adults. The Food and Drug Administration (FDA) have approved zolpidem for use in certain 
sleep disorders, specifically in the treatment of sleeplessness (i.e., insomnia).  In the current study, we 
will examine whether zolpidem (5mg), compared with placebo, increases memory-related sleep events 
in older adults and test the impact of these drug-related sleep changes on post-sleep memory recall. 
 
This is a research study because we are using pharmacological interventions to investigate our 
hypotheses about memory consolidation. We are not investigating the efficacy of zolpidem to treat 
conditions for which the FDA has already approved it. 
 
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SECTION 1: PURPOSE AND BACKGROUND OF THE RESEARCH  
 
1. Provide the scientific or scholarly rationale for the research.  Describe the relevant background 
information and the specific gaps in current knowledge that this study intends to address.  
Sleep quality, efficiency and continuity are all known to decrease with age (Spira et al. 2012; Stranges 
et al. 2012). One example of this is that spindle density, amplitude and duration are reduced in older 
adults compared with young subjects (Guazzelli et al. 1986; Wei et al. 1999; Crowley et al. 2002). This 
decline has been shown to be progressive through the aging process (Principe et al. 1982; Nicolas et 
al. 2001). Other studies have demonstrated decreases in spectral power in the spindle frequency 
range (i.e., sigma activity; 12.25–14 Hz) as early as middle age (Dijk et al. 1989; Landolt et al. 1996; 
Carrier et al. 2001). Disruptions have also been reported for slow wave sleep (SWS), specifically 
decreased slow wave activity (SWA) (.5-5Hz) (Dijk et al. 1989; Van Cauter et al. 2000). Co-occurring 
with these sleep impairments is the cognitive hallmark of aging: a progressive deterioration of 
declarative memory (Alexander et al. 2012). A primary deficit in aging is a deficit in associative 
memory (Chalfonte et al. 1996; Mitchell et al. 2000; Naveh-Benjamin 2000). This pattern has been 
observed with word (Castel et al. 2003), word-spatial location (Mitchell et al. 2000), word-font (Naveh-
Benjamin et al. 2003), name-face (Naveh-Benjamin et al. 2004; Miller et al. 2008) and face-face pairs 
(Bastin et al. 2003). Age-related impairments in declarative associative learning are correlated with 
reductions in hippocampal activity as well as dorsolateral prefrontal activity (Dennis 2008). Recent 
studies examine the possibility that these age-related memory deficits, at least in part, may be from 
disrupted sleep, perhaps disrupted sleep spindles (12-15 Hz electrophysiological signals during sleep 
associated with memory consolidation). The current research study will measure specific sleep events 
(i.e., sleep spindles) in older adults and examine their role in sleep-dependent memory. We will use 
zolpidem as a tool to increase sleep spindles in order to examine whether spindles are critically 
important for memory consolidation during sleep in older adults. 
2. Provide relevant preliminary data (animal and/or human).   
 We refer to two pharmacology/sleep studies that are relevant to the proposed work. First, we 
conducted a dose response study of ZOL (5mg & 10mg) to determine the optimal dose of ZOL for 
increasing the density of Stage Two sleep spindles in young adults (Brunner et al. 1991; Feinberg et 
al. 2000). The nap was scheduled to occur at 8:30AM to capitalize on circadian fluctuations in REM 
sleep (highest in the morning). This allowed us to maximize differences in sleep stages between the 
drug and placebo conditions. Results from this study showed that 1) 10mg dose of zolpidem was 
sufficient to pharmacologically-modulated sleep spindles in youngers, and 2) demonstrated our ability 
to effectively conduct a dose-response investigation using pharmacological intervention (Mednick et al. 
2015).  
Next, we conducted a study in young adults investigating the effect of the three pharmacological 
interventions (10mg ZOL, 2.5g SO, and placebo) on four memory domains: verbal, motor, perceptual 
and emotional memory (Mednick et al. 2015). The encoding session began at 6AM, the drug-
enhanced nap occurred at 8:30AM, and retrieval occurred at 3PM on the same day. As predicted, 
compared with placebo, ZOL improved verbal memory, but decreased perceptual learning. No 
changes were found for motor learning across drug conditions. Furthermore, these performance 
changes were associated with changes in specific sleep features. In line with prior studies, ZOL 
increased sleep spindle density and decreased REM sleep, but these changes did not affect motor 
learning. Verbal memory performance was significantly correlated with spindle density in ZOL (r=0.38, 
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p=0.02), and placebo (r=0.34, p=0.02), and marginally in SO (r=0.29, p=0.08). As we had 
hypothesized, perceptual learning was negatively correlated with spindle density in placebo (r=-0.41, 
p=0.02) and SO  (r=-.50, p=0.006), but not ZOL (p>0.44). For motor memory, a negative correlation 
with spindle density was found in SO (r=-0.38, p=0.03), whereas a positive correlation was found in 
placebo (r=0.35, p=0.05), and no correlation was found in ZOL (p>0.45).  
In order to further probe the relationship between Stage Two spindle density and enhancements in 
verbal memory independent of the drug conditions, we employed Analysis of Co-Variance (ANCOVA) 
using verbal memory performance as the dependent variable, drug condition as the independent 
variable, and spindle density as the covariate. The ANCOVA showed that when spindle density is 
accounted for, the main effect of drug condition disappeared (p=0.40), while the spindle density effect 
on performance was highly significant (p<0.001). Taken together, these results indicate that the verbal 
memory improvements with ZOL may represent an enhancement of a normal consolidation process 
during sleep, since similar correlations between spindles and verbal memory were found in all three 
drug conditions. In addition, the experimental manipulation of spindles and associated increases in 
verbal memory raise the possibility that sleep spindles may represent physiological processes critical 
for declarative verbal memory consolidation, evinced by the significant effect of spindles on 
performance in the ANCOVA analysis. Importantly, we did not find improved verbal memory to be 
related to any other sleep features (e.g., sleep duration, sleep efficiency, etc.) whether in the placebo 
condition or in changes associated with either of the active drugs.  
For emotional memory, as hypothesized, memory discrimination (da) for negative stimuli (p=0.03) and 
high arousal (p=0.04) was significantly better in the ZOL condition compared with placebo. No 
differences were found in positive, neutral or low arousal emotional memories across drug conditions. 
Spindle density was correlated with negative valence and high-arousal memory in SO but not placebo 
or ZOL. This discrepancy may be indicative of a ceiling effect in spindles in the placebo and ZOL 
conditions, whereas decreases in spindles in the SO condition produced a greater range of spindles, 
leading to a significant correlation with memory performance. This hypothesis will be tested in older 
adults who show decreased spindles (Guazzelli et al. 1986; Wei et al. 1999; Crowley et al. 2002). In 
this population, we hypothesize that correlations between spindle density and emotional memory 
performance will also be found. Of note, differences in discrimination were not accompanied by 
alterations in measures of bias (ca). Interestingly, we did not find any changes associated with REM 
sleep, except a significant correlation between REM and low arousal pictures, which is somewhat 
consistent with our hypothesis that spindles increase consolidation of emotional memories, and REM 
sleep increases processing of emotional arousal (Baran et al. 2012).  
These studies demonstrate the specificity of sleep-dependent memory with respect to: 1) sleep feature 
(i.e., increased Stage Two sleep spindle density), 2) memory domain (i.e., increased declarative 
associative verbal and emotional memory, compared with non-declarative motor and perceptual 
learning), 3) pharmacological intervention (i.e., ZOL increased memory, compared with SO and 
placebo). Furthermore, we demonstrate our capacity for successfully carrying forth the proposed 
pharmacology, sleep, and memory studies.  
 
Limitations of the pilot study, and their solutions:  
 
Localization of sleep spindles: A major limitation of the pilot study was the electrode 
configuration (i.e., no frontal sites), which prevented accurate assessment of sleep spindles in 
SWS or localization of spindles (frontal versus central) (Molle et al. 2011). Therefore, our 
analysis was confined to Stage Two sleep spindles at central sites. The proposed studies will 
record from 64 electrode sites to better measure the topography of spindles in all stages of 
NREM sleep. This improvement will allow us to dissociate the functional significance of 
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spindles in Stage Two and SWS, as well as differences between local and global sleep effects 
on memory consolidation. Furthermore, topographical changes in spindles have been found in 
older adults (i.e., decreased density of frontal spindles). We will examine whether behavioral 
changes due to the pharmacological intervention will be associated with changes to spindles in 
frontal or central sites in older adults.  
 
Automated Spindle Detection: Two major limitations to the prior data are that all spindles were 
hand-counted, and spindle morphology (amplitude, frequency, and duration) was not analyzed. 
In the current studies we will increase sophistication of analysis techniques of sleep spindles. 
This will allow us to examine 1) if the memory improvements were associated with fast or slow 
spindles, coupling with other electrophysiological events, 2) if the drugs changed additional 
aspects of spindles including amplitude, frequency and duration, and 3) if those changes were 
associated with performance changes. These advancements will hugely impact profundity of 
the conclusions we can draw from our results regarding the specificity of sleep for memory 
consolidation.  
 
Task Interference: The pilot study tested four tasks in a single session, which increased task 
interference. The proposed study will decrease task interference by testing only two memory 
tasks, declarative and non-declarative memory. This will provide a precise measurement of the 
magnitude of the drug effects on two memory domains that rely on non-overlapping neural 
mechanisms. 
 
Older adults dosage: Although we used a 10mg dose for younger adults, we will be using a 
5mg dose for older subjects as this dose is a standard dose for this age group, and the 5mg 
dose did modulate sigma activity in younger subjects as well. 
 
3. Describe the purpose, specific aims or objectives.  Specify the hypotheses or research questions to 
be studied. 
 
SPECIFIC AIM 1. To compare the effect of zolpidem versus placebo on sleep-dependent memory in  
declarative and non-declarative memory task in older adults. 
Hypothesis 1A: Declarative memory will be improved after a nap with zolpidem compared to placebo. 
Hypothesis 1B: Non-Declarative memory will show no differences between zolpidem and placebo. 
 
SPECIFIC AIM 2: To assess sleep stages and spindles morphology (frequency, amplitude, and 
duration) in a nap with zolpidem versus placebo and their correlation with performance in older adults.  
Hypothesis 2A: Improved declarative memory in the zolpidem condition will be mediated by the 
number of spindles in the naps of older adults.  
Hypothesis 2B: Non-declarative memory in older adults will be mediated by the amount of REM sleep 
in both drug conditions. 
Hypothesis 2C: Zolpidem will increase sleep spindles, compared with placebo. 
 
4. Describe the primary outcome variable(s), secondary outcome variables, and predictors and/or 
comparison groups as appropriate for the stated study objectives/specific aims.     
Our primary outcomes variable will be the level of memory recall. Specifically, we will assess memory 
performance change between baseline recall and post-intervention recall tests. We expect that 
zolpidem will improve memory recall compared to placebo. 
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Our secondary outcome variables will be electrophysiological activity during the naps. We expect that 
zolpidem will increase the activity of sleep spindles compared to placebo. 
Our main comparison will be the experimental conditions (1) zolpidem, and 2) placebo. 
 
We will examine several electrophysiological markers (spindles activity: fast and slow spindle density, 
amplitude and frequency) as predictors of memory performance.  
5. List up to ten relevant references/articles to support the rationale for the research. Do not append an 
extensive NIH-grant-style bibliography. 
Spira, A. P., K. Covinsky, et al. (2012). "Poor sleep quality and functional decline in older women." J Am 
Geriatr Soc 60(6): 1092-1098. 
Spira, A. P., K. Covinsky, et al. (2012). "Objectively measured sleep quality and nursing home placement 
in older women." J Am Geriatr Soc 60(7): 1237-1243. 
Guazzelli, M., I. Feinberg, et al. (1986). "Sleep spindles in normal elderly: comparison with young adult 
patterns and relation to nocturnal awakening, cognitive function and brain atrophy." 
Electroencephalogr Clin Neurophysiol 63(6): 526-539. 
Wei, H. G., E. Riel, et al. (1999). "Attenuated amplitude of circadian and sleep-dependent modulation of 
electroencephalographic sleep spindle characteristics in elderly human subjects." Neurosci Lett 
260(1): 29-32. 
Crowley, K., J. Trinder, et al. (2002). "The effects of normal aging on sleep spindle and K-complex 
production." Clin Neurophysiol 113(10): 1615-1622. 
Nicolas, A., D. Petit, et al. (2001). "Sleep spindle characteristics in healthy subjects of different age groups." 
Clin Neurophysiol 112(3): 521-527. 
 Dijk, D. J., D. G. Beersma, et al. (1989). "All night spectral analysis of EEG sleep in young adult and 
middle-aged male subjects." Neurobiol Aging 10(6): 677-682. 
Landolt, H. P., D. J. Dijk, et al. (1996). "Effect of age on the sleep EEG: slow-wave activity and spindle 
frequency activity in young and middle-aged men." Brain Res 738(2): 205-212. 
Carrier, J., S. Land, et al. (2001). "The effects of age and gender on sleep EEG power spectral density in 
the middle years of life (ages 20-60 years old)." Psychophysiology 38(2): 232-242. 
Van Cauter, E., R. Leproult, et al. (2000). "Age-related changes in slow wave sleep and REM sleep and 
relationship with growth hormone and cortisol levels in healthy men." JAMA 284(7): 861-868. 
Langtry, H.D. and Benfield, P. Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties 
and therapeutic potential. Drugs. 1990; 40: 291–313 
 
 
 
SECTION 2: ROLES AND EXPERTISE OF THE STUDY TEAM  
 
1. List all research team members who will interact or intervene with human subjects or will have 
access to identifiable private information about human subjects. Include additional rows for Co-
researchers and Research Personnel, as needed. 
2. For each research team member, indicate all applicable research activities the individual will 
perform.  Finalizing informed consent is reviewing, answering/asking questions, confirming 
competency, as necessary, and signing/confirming the informed consent. 
3. If applicable, list the Faculty Sponsor as a Co-Researcher who will have research oversight 
responsibilities. 
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Lead Researcher:   
Name and Degree:  Sara C. Mednick, PhD 
Position/Title and Department:  Associate Professor, Department of Cognitive Sciences 
Team Member will:  [  x ] Screen/Recruit    [  x ] Finalize Informed Consent    
[  x ] Perform Research Activities (describe below)    [ x  ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience):  
Research activities/procedures: study design, recruitment, informed consent (signing/confirming), 
interact with participants, answering questions, confirming eligibility, analyzing participant data, 
disseminating results. 
 
Qualification: Completion of CITI and HIPAA training. Her background in sleep and memory research, 
with a focus on aging provides adequate support for both the sleep-dependent learning aspect of this 
project and the older adults research. In 2003, she received her PhD in psychology from Harvard 
University working with Ken Nakayama and Robert Stickgold. She moved to the Salk Institute for 
Biological Studies in La Jolla, CA with a three-year, National Institute of Health funded, National 
Research Service Award fellowship, where she trained with Geoffrey Boynton and Sean Drummond. In 
fall 2007, she became faculty at University of California, San Diego and was awarded a five-year, 
National Institute of Mental Health funded, K01 Mentored Research Scientist Award. In 2011, Dr. 
Mednick moved her lab to UC Riverside. Most recently, Dr. Mednick has moved her lab to UC Irvine 
where she continues to conduct research. Dr. Mednick has conducted studies in conjunction with 
numerous academic institutions, the U.S. Navy, V.A. Medical Center and private businesses. Her articles 
have been published in such leading scientific journals as Nature Neuroscience and The Proceedings 
from the National Academy of Science.  
Co-Researcher: 
Name and Degree:  Steven C. Cramer, MD 
Position/Title and Department:  Professor, UCI School of Medicine 
Team Member will:    [   ] serve as Faculty Sponsor with research oversight responsibilities  
[ x ] Screen/Recruit    [ x  ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [  x ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: interact with participants, answering questions, perform physical 
examinations, collect and interpret medical history, and prescribe Zolpidem tartrate for the 
use described in this study. 
 
Qualification: Dr. Steven C. Cramer is a Professor of Neurology, Anatomy & Neurobiology, and 
Physical Medicine & Rehabilitation at the University of California, Irvine. He is also the Clinical Director 
of the Sue & Bill Gross Stem Cell Research Center and Associate Director of the UC Irvine Institute for 
Clinical & Translational Science at UC Irvine, and co-PI of the NIH StrokeNet. Dr. Cramer graduated 
with Highest Honors from University of California, Berkeley; received his medical degree from 
University of Southern California; did a residency in internal medicine at UCLA; and did a residency in 
neurology plus and a fellowship in cerebrovascular disease at Massachusetts General Hospital. He 
also earned a Masters Degree in Clinical Investigation from Harvard Medical School. 
 
His research focuses on neural repair after central nervous system injury in humans, with an emphasis 
on stroke and recovery of movement. Treatments examined include robotic, stem cell, brain 
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stimulation, biologic, drug, and telehealth methods. A major emphasis is on translating new drugs and 
devices to reduce disability after stroke, and on individualizing therapy for each person’s needs. Dr. 
Cramer co-edited the book “Brain Repair after Stroke” and is the author of over 250 manuscripts 
Co-Researcher: 
Name and Degree:  Sara Stern-Nezer, MD 
Position/Title and Department:  Assistant Professor, UCI School of Medicine 
Team Member will:    [   ] serve as Faculty Sponsor with research oversight responsibilities  
[ x ] Screen/Recruit    [ x ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [  x ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience):  
Research activities/procedures: interact with participants, answering questions, perform physical 
examinations, collect and interpret medical history, and prescribe Zolpidem tartrate for the 
use described in this study. 
 
Qualification: Dr. Sara Stern-Nezer is an Assistant Clinical Professor in the Department of Neurology 
at the UC Irvine School of Medicine. She is also a writer and editor for the Neurocritical Care Society. 
Dr. Stern-Nezer received her medical degree from Stanford University in 2011 and completed her 
residency in neurology at Stanford Health Care in 2015. She also holds an MPH, specializing in 
epidemiology and biostatistics, from UC Berkeley.  
 
Co-Researcher: 
Name and Degree:  Paola Malerba, PhD 
Position/Title and Department:  Faculty, Department of Cognitive Science 
Team Member will:    [   ] serve as Faculty Sponsor with research oversight responsibilities  
[ x ] Screen/Recruit    [ ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [  x ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: study design, recruitment, interact with participants, answering 
questions, confirming eligibility, analyzing participant data, disseminating results. 
 
Qualification: Paola obtained a PhD in Mathematics at Boston University in 2010 and she applies 
mathematical analysis and modeling to the understanding of brain rhythms. Within SaC Lab, she has 
studied the spatio-temporal patterns of slow oscillations on the electrode manifold. Using k-clustering 
and relative detection probability we have found that slow oscillations were clustered in three types: 
Global, Local or Frontal depending on their footprint on the electrode manifold during a time window. 
Global slow oscillations showed the strongest relationship with sleep spindles, both in amplitude and 
probability of detection. This research is laying the foundation for modeling work on the spatio-
temporal occurrence of slow oscillations and spindles on the electrode manifold, to study how closed-
loop stimulation during sleep changes sleep waves and possibly memory performance. 
 
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Co-Researcher: 
Name and Degree:  Trisha Maris (Hufnagel), B. Pharm 
Position/Title and Department:  Investigation Drug Pharmacist/Specialist 
Team Member will:    [   ] serve as Faculty Sponsor with research oversight responsibilities  
[ x  ] Screen/Recruit    [   ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [  x ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: provide the placebo and perform drug randomization 
 
Qualification: Maris received her B.S. in General Chemistry from the University of California, Los 
Angeles and her B. Pharm in Pharmacy from Ohio State University. Before accepting the role of 
investigational drug pharmacist at UC Irvine Health in 2015, she excelled in her role as outpatient 
pharmacist lead for 12 years at UC Irvine Health (2005-2017).   
Co-Researcher: 
Name and Degree:  Negin Sattari Barabadi, M.A. 
Position/Title and Department:  Graduate Student, Department of Cognitive Sciences 
Team Member will:    [   ] serve as Faculty Sponsor with research oversight responsibilities  
[ x  ] Screen/Recruit    [   ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [  x ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: study design, recruitment, interact with participants, answering 
questions, confirming eligibility, analyzing participant data, disseminating results. 
 
Qualification: Completion of CITI and HIPAA training.  She received her B.S in Computer Science from 
Iran and her MA in psychology from University of California, Riverside. Negin's research interests 
entail in the effect of sex hormones on sleep-related memory consolidation and learning. Negin also 
studied the effect of napping among older adults during her master’s thesis. 
Co-Researcher: 
Name and Degree:  Pin-Chun Chen, BS 
Position/Title and Department:  Graduate Student, Department of Cognitive Sciences 
Team Member will:  [ x  ] Screen/Recruit    [   ] Finalize Informed Consent   
[x   ] Perform Research Activities (describe below)    [ x  ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience):  
Research activities/procedures: recruitment, interact with participants, answering questions, confirming 
eligibility, analyzing participant data. 
 
Qualification: Completion of CITI and HIPAA training and has more than 3 years experience interacting 
with subjects and running a human subject study. 
 
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Co-Researcher: 
Name and Degree:  Frida Corona, BS 
Position/Title and Department:  Graduate Student, Department of Cognitive Sciences 
Team Member will:  [ x  ] Screen/Recruit    [   ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [ x  ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: recruitment, interact with participants, answering questions, confirming 
eligibility, analyzing participant data. 
 
Qualification: Completion of CITI and HIPAA training and has more than 3 years experience interacting 
with subjects and running a human subject study. 
Co-Researcher: 
Name and Degree:  Tenzin Tselha, M.S. 
Position/Title and Department:  Graduate Student, Department of Cognitive Sciences 
Team Member will:  [ x  ] Screen/Recruit    [   ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [ x  ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience): 
Research activities/procedures: recruitment, interact with participants, answering questions, confirming 
eligibility, analyzing participant data. 
 
Qualification: Completion of CITI and HIPAA training and has more than 4 years’ experience 
interacting with subjects and running a human subject study. 
Research Personnel: 
Name and Degree:  Lexus Hernandez, BA 
Position/Title and Department:  Lab Technician, Department of Cognitive Sciences 
Team Member will:  [  x ] Screen/Recruit    [  ] Finalize Informed Consent    
[ x  ] Perform Research Activities (describe below)    [ x  ] Access subject identifiable data 
List the research activities/procedures to be performed and the individual’s relevant qualifications 
(training, experience):  
Research activities/procedures: recruitment, interact with participants, answering questions, confirming 
eligibility, analyzing participant data. 
Qualification: Completion of CITI and HIPAA training and has more than 3 years experience interacting 
with subjects and running a human subject study.  
 
SECTION 3: SUBJECT POPULATION(S) (INDIVIDUALS/RECORDS/SPECIMENS) 
 
A. 
Subjects To Be Enrolled on this UCI protocol (Persons/Records/Biospecimens) 
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1. Complete the table of subject enrollments below.  Include additional rows for subject category/group, 
as needed. 
2. If the study involves the use of existing records or biological specimens, specify the maximum 
number to be reviewed/collected and the number needed to address the research question. 
Category/Group  
(e.g., adults, controls, parents, 
children) 
Age Range 
(e.g., 7-12, 13–17, 
adults) 
Maximum Number 
to be Consented or 
Reviewed/Collected 
(include withdrawals 
and screen failures)  
Number 
Expected to 
Complete the 
Study or Needed 
to Address the 
Research 
Question 
Adults 
60-75 
60 
45 
 
Total: 60 
 
 
B. Overall Study Sample Size 
If this is a multi-site study, provide the total number of subjects to be enrolled from all sites. 
[ x ] Not applicable: This study will only take place at UCI, and does not involve other sites. 
Total number of subjects across all sites:  <Type here> 
 
C.  Eligibility Criteria 
1. Identify the criteria for inclusion and exclusion. 
Subjects will be screened for neurological disorders (e.g., Parkinson’s disease, dementia, stroke) using 
several perceptual and cognitive tests (e.g., Digit Span Forward, Digit Span Backward). Inclusion 
criteria include ages 60-75, healthy with normal to corrected normal vision, at least 12 years of 
education and having a non-polarized chronotype (defined as a Horne-Ostberg Morningness-
Eveningness Questionnaire score between 9 to 24), and prior experience with zolpidem.  
 
Exclusionary criteria include:  a) having a sleep disorder (reported or detected on the questionnaires); 
b) any personal or immediate family (i.e., first degree relative) history of diagnosed significant 
psychopathology; c) personal history of head injury with loss of consciousness greater than 2 minutes 
or seizures; d) history of substance dependence; e) current use of any medications that could effect 
sleep and/or cognition; f) any cardiac, respiratory or other medical condition which may affect cerebral 
metabolism (Subjects with a heart rate lower than 50 beats per minute or with blood pressure readings 
less than 90 mmHg (systolic) or 60 mmHg (diastolic) will be excluded) ; g) dementia using Mini Mental 
Status exam questionnaire I) Given the nature of the stimuli and presentation, anyone with non-
correctable vision and audition impairments will also be excluded. 
 
The contraindications for zolpidem include: alcohol intoxication, attention deficit disorder with 
hyperactivity, history of parasomnias (complex/abnormal behaviors during sleep), severe chronic 
obstructed lung disease, liver problems, hangover, loss of memory, hallucinations, having thoughts of 
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suicide. Prior to subsequent study visits, participants will be asked to review their responses on the 
screening form and to verify that none of the responses have changed. 
 
Subjects will be screened for inclusion and exclusion criteria with an approved screening 
questionnaire.   
2. If eligibility is based on age, gender, pregnancy/childbearing potential, social/ethnic group, or 
language spoken (e.g., English Speakers only), provide a scientific rationale. 
[   ] Not applicable: Subject eligibility is not based on these factors. 
We propose to study a healthy older adult population (60-75). Physical and psychological health is 
important for this study in order to avoid adverse effects on sleep. An education requirement of at least 
12 years completed will be imposed, as education may affect performance on the cognitive tasks. We 
will be studying English speakers only, as second languages are processed differently than primary 
languages in the brain. We propose a large sample size in order to collect enough data to analyze 
individual differences in sleep-dependent learning for different memory domains. The PI's previous 
studies report about a 25% percent attrition rate. 
 
SECTION 4: RECRUITMENT METHODS  
 
Check any of the following methods that will be used to recruit subjects for this study: 
[   ] This study involves no direct contact with subjects (i.e., use of existing records, charts, 
specimens). 
 
Specify database or IRB-approved protocol number (HS#), if applicable: <Type here> 
[ x ] Advertisements, flyers, brochures, email, Facebook, and/or other media.   
Specify where recruitment materials will be posted: Flyers will be posted at retirement communities, 
senior centers, senior living communities, UCI campus, and other areas where there is a large 
presence of older adults. Advertisements will also be posted on Craigslist and Facebook (via 
groups and on personal pages of research personnel).  
If subjects will be recruited by mail, e-mail, or phone, specify how their contact information will be 
obtained:  
We will also use a direct mailing company, Direct Connection, that will send the attached 
recruitment letter to approximately 8000 older adults in the Irvine community.  
We will submit a mail list request to the ZotMail team in order to email our approved online script to 
all UCI faculty members and employees. The ZotMail team will send out the recruitment emails. If 
the faculty members/ employees are interested in this study, they will contact the study team. The 
study team will not access the list of emails, so we will not compromise their privacy/ confidentiality. 
Submit recruitment materials for IRB approval. 
[  x ] The study will be listed on Clinicaltrials.gov. All clinical research must be registered.  
[   ] The study will be listed on the UC Irvine Health Clinical Trials web page.  
Submit the UCIMC Standard Research Recruitment Advertisement for IRB approval.   
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[   ] The UCI Social Sciences Human Subjects Lab/Sona Systems will be used.   
Submit the Social Science Human Subject Pool Recruitment Advertisement for IRB approval. 
[   ] Referral from colleagues  
 
Study team will provide colleagues with UCI IRB-approved recruitment materials for 
distribution to potential subjects (e.g., recruitment flyer, introductory letter);  
 
An IRB-approved recruitment letter will be sent by the treating physician.  The letter will be 
signed by the treating physician and sent to his/her patients to inform them about how to 
contact study team members; and/or 
 
Colleagues obtain permission from interested patient to release contact information to 
researchers.  
 
Study team does not have access to patient names and addresses for mailing.  
 
If colleagues will screen their patients’ medical records to determine subject eligibility and 
approach patients directly about study participation: Complete Appendix T to request a 
partial waiver of HIPAA Authorization. 
Submit recruitment materials for IRB approval. 
[ x  ] Study team will contact potential subjects who have given prior permission to be contacted for 
research studies.  
Specify when and how these individuals granted permission for future contact: Recruitment will 
also occur through the Consent-to-Contact registry (C2C). The study team will request the contact 
information from subjects who have submitted data to the C2C registry and who have given 
permission to be contacted regarding participation in research studies. 
 
Specify database or IRB-approved protocol number (HS#): 2015-2494 
[   ] Study team members will approach their own patients, students, employees for participation in the 
study. 
[   ] Study team will screen UCIMC medical records to which they have access to determine subject 
eligibility. The patients’ physicians will approach patients directly about study participation. 
 
Complete Appendix T to request a partial waiver of HIPAA Authorization. 
[   ] Other Recruitment Methods: <Indicate the recruitment method(s) here> 
 
SECTION 5:  INFORMED CONSENT PROCESS  
 
A. 
Methods of Informed Consent 
1. Indicate all applicable informed consent methods for this study. Submit the consent/assent 
document(s) with your e-IRB Application (e.g., Study Information Sheet, Recruitment script, 
Consent Form, etc.). Only IRB approved consent forms (containing the IRB approval footer) may 
be used to consent human subjects at UCI. 
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[ x ] Written (signed) informed consent will be obtained from subjects.  Signed informed consent, 
parental permission, and/or child assent will be obtained from subjects, as applicable.  
[ x ] Requesting a waiver of written (signed) informed consent.  Signed consent will not be 
obtained; consent will be obtained verbally or via the web. Informed consent, parental permission 
and/or child assent will be obtained from subjects, as applicable.    
Complete Appendix P.  
[   ] Requesting to seek surrogate consent from a legally authorized individual. Surrogate 
consent may be considered only in research studies relating to the cognitive impairment, lack of 
capacity or serious or life-threatening disease and conditions of the research subjects. 
Complete Appendix E.  
[   ] Requesting a waiver of informed consent. (i.e., consent will not be obtained). Skip to Section 
5.B. 
Complete Appendix O.  
2. Indicate where the consent process will take place.  
[ x ] In a private room 
[   ] In a waiting room 
[   ] In an open unit 
[   ] In a group setting 
[   ] The internet 
[   ] In public setting  
[   ] Over the phone  
[   ] Other (specify): <Type here> 
3. Specify how the research team will assure that subjects have sufficient time to consider whether to 
participate in the research. 
[  x ] Subjects will be allowed to take home the unsigned consent form for review prior to signing it.  
[   ] Subjects will be allowed <Type here> hours to consider whether to consent.  
[ x ] Other (specify): Eligible participants will be contacted via email and/or telephone to see if they are 
still interested in participating. If they still are, the research team will set up and appointment to meet 
with them to go over the consent form and other approved documents that are study-related. This 
meeting will take place at the UC Irvine Institute for Clinical and Translational Science (ICTS), subjects 
will be provided with free parking. During this appointment, eligible participants will be given 45 
minutes (if needed, they will be given additional time) to read over the consent form and jot down any 
questions or concerns they may have. Afterwards, a member from the research team will go through 
all sections of the consent form with the individual and answer any questions they may have along the 
way. Once all sections are discussed and all questions have been answered, subjects will have the 
opportunity to decide if they want to participate in the study or not. If they agree to participate, the 
member from the research team will ask them to sign two copies of the consent form (one copy will be 
given to the participant for their own records) and the research team member will also sign both 
copies. If they are unsure if they want to participate, the research team member will give them an 
unsigned copy of the consent form to take home and will follow up with them in 1-2 days. If the subject 
decides not to participate in the study, they will be thanked for volunteering their time to come in for an 
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appointment and an unsigned consent form will be given for their records. Additionally, there will be no 
future communication initiated from the research team.  
4. If children are enrolled in this study, describe the parental permission process and the child assent 
process.   
[  x ] Not applicable: Children are not enrolled in this study. 
<Type here> 
5. Some subjects may be vulnerable to coercion or undue influence, such as those who are 
economically or educationally disadvantaged, mentally disabled, or students (undergraduate, 
graduate, and medical students) and employees of UCI (administrative, clerical, nursing, lab 
technicians, post-doctoral fellows and house staff, etc.), describe the procedures to ensure the 
voluntary participation of these individuals. 
[ x  ] Not applicable: Subjects are not vulnerable to coercion or undue influence. 
  
[  ] Other (specify):  <Type here> 
 
B. Health Insurance Portability and Accountability Act (HIPAA) Authorization 
Indicate all applicable HIPAA authorization methods for this study. 
[   ] Not applicable: Study does not involve the creation, use, or disclosure of Protected or Personal 
Health Information (PHI). 
[   ] Requesting a Total waiver of HIPAA Authorization. HIPAA authorization will not be obtained at 
all for the study.  
Complete Appendix T.   
[   ] Requesting a Partial waiver of HIPAA Authorization. HIPAA authorization will not be obtained 
for screening/recruitment purposes. However, written (signed) HIPAA research authorization is 
obtained for further access to personal health information.  
Complete Appendix T.   
 [ x ] Written (signed) HIPAA Research Authorization will be obtained from subjects. Signed 
authorization, parental authorization, and/or child assent will be obtained from subjects, as 
applicable.   
Complete the HIPAA Research Authorization form.   
 
C. Methods of Informed Consent for non-English Speakers 
1. Indicate the applicable informed consent method for non-English speakers.  
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[  x ] Not applicable: Only individuals who can read and speak English are eligible for this study. 
Scientific justification must be provided in Section 3.C.2. 
[   ] The English version of the consent form will be translated into appropriate languages for non-
English speaking subjects once IRB approval is granted. The translated consent form must be 
submitted to the IRB for review prior to use with human subjects.  Only IRB approved consent 
forms (containing the IRB approval stamp) may be used to consent human subjects at UCI.   
[   ] Requesting a short form consent process.  
Complete Appendix Q.  
       The short form process will be used for the following occasional and unexpected languages:  
[   ] All non-English languages  
[   ] All non-English languages except Spanish  
[   ] Other languages (specify): <Type here>  
2. Explain how non-English speaking subjects will be consented in their language and who will be 
responsible for interpreting and facilitating the informed consent discussion for the non-English 
speaking subjects.   
[   ] At least one member of the study team is fluent in the language that will be used for 
communication, and that study team member(s) will be available during emergencies.   
For all members of the study team responsible for obtaining informed consent from non-
English speaking subjects, provide their qualifications to serve in this capacity (i.e. language 
fluency) in Section 2. 
[   ] The study team has 24-hour access to a translation service with sufficient medical expertise to 
discuss the research in this study.  
[   ] Other (explain): <Type here> 
 
SECTION 6: RESEARCH METHODOLOGY/STUDY PROCEDURES 
 
A. 
Study Location 
Specify where the research procedures will take place (e.g. UCI Douglas Hospital – Cardiac Care Unit, 
UCI Main Campus Hewitt Hall, UCI Health – Pavilion II, UCI Family Health Center, Anaheim, Irvine High 
School).  
If research activities will also be conducted at non-UCI locations (e.g., educational institutions, 
businesses, organizations, etc.), Complete Appendix A. Letters of Permission or other documentation 
may be required (e.g. Off-site Research Agreements or IRB Authorization Agreements). 
The majority of all study appointments will be held at the UC Irvine Institute for Clinical and 
Translational Science (ICTS), the UCI Main Campus location and the UCI Orange Medical Center 
location. We will put both locations on the consent form due to availability changing on a weekly basis. 
On occasion, when the ICTS is closed, we will hold our non-medical screening appointments at the 
Sleep and Cognition (SaC) lab in the Social Science Research building, room 380. Subjects who 
remain eligible after this appointment will be scheduled for a medical history and physical appointment 
at the ICTS. 
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B. 
 Study Design  
1. Include an explanation of the study design (e.g., randomized placebo-controlled, cross-over, cross-
sectional, longitudinal, etc.) and, if appropriate, describe stratification/ randomization/blinding 
scheme.  
The research involves oral administration of zolpidem (ZOL) or placebo during sleep with EEG 
recording. A randomized, crossover design under double-blind conditions will be utilized. This study 
will employ a within-subject, crossover design, in which every subject experiences each of the 
following study conditions: Nap/5mg, Nap/placebo, plus an adaptation nap at the ICTS to be 
scheduled one week prior to the first experimental day. One condition will be tested per week, with 
condition order counterbalanced. The pharmacist will ensure that subjects who initially receive 
Zolpidem will get the placebo pill a week after and vice versa. Thus, each subject will have 2 visits 
(plus an adaptation nap), each separated by 5-7 days (although this may be extended based on 
participant availability) to ensure that the drug is completely eliminated from the body. The order of 
drug conditions will be randomized and counterbalanced. During the experimental phase, each drug 
condition will include one day in the sleep lab, two encoding test sessions, and one retrieval test 
session. Multiple subjects will be in the experimental phase concurrently, and multiple subjects will be 
tested on each day. 
 
2. Provide precise definitions of the study endpoints and criteria for evaluation; if the primary outcomes 
are derived from several measurements (i.e., composite variables) or if endpoints are based 
composite variables, then describe precisely how the composite variables are derived. 
Study endpoints will be the completion of data collection with respect of a priori decision on sample 
size. 
 
C. 
Research Procedures 
1. Provide a detailed chronological description of all research procedures.   
Participants will call or email the lab if they are interested in participating in the study. Eligibility 
determination will occur in three steps. Initial screening of subjects will take place with screening 
survey. Those who are not excluded for obvious violations of eligibility criteria will then be invited to the 
ICTS for an in-person interview during which informed consent will be thoroughly reviewed with the 
subject and they will be required express their understanding of the protocol and what is being asked 
of them at various places throughout the informed consent.  
 
Eligible subjects will then return for an orientation at the UCI ICTS. At orientation, subjects will 
experience: 1)  signing of consent form, 2) a Structured Clinical Interview for DSM disorders (SCID-5) 
conducted by a trained research assistant, 3) an EEG-monitored adaptation nap opportunity, 4) 
signing of the Health Insurance Portability and Accountability (HIPAA) form to ensure ICTS can share 
eligibility discrepancies with appropriate research personnel, 5) cognitive testing: Digit Span 
Forward/Backward, Stroop task, and the Symbol Digit task.  
 
Subjects who remain eligible after this appointment will be scheduled for a final screening 
appointment, which will include a medical history and physical. During this appointment, blood 
pressure and heart rate will be measured. Urine toxicology screens will also be taken during this 
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appointment and a complete drug panel will be run by the ICTS. Participants with a positive drug 
screen will be excluded from participation. Following the medical history and physical appointment, 
subjects will be invited to participate in the full study.  
 
Prior to leaving the medical appointment, subjects will be given an actigraph, a wrist activity monitor 
the size of a watch that measures movement. Participants will also be asked to complete a sleep diary 
for 7 nights prior to their in-lab visits. The sleep diary is available via a secure online website link 
provided to the participant. However, paper copies of the sleep diary will be available upon request 
from the participant.   
 
Participants will be asked to abstain from caffeine and alcohol 48 hours prior to and including each 
study session. 
 
Subjects will be instructed to spend 8 hours time-in-bed (10pm-6am) the night before each study day. 
All subjects will remain in the lab for the entirety of the visit day (7am-9pm). For each visit, subjects will 
report to the UCI ICTS at 6:30am. From 7am-8:30am (test session 1) subjects will complete two 
cognitive tasks (word-pair associates and finger tapping task) described below. Subjects will have 
electrodes attached from 8:30am-9am, and will be provided a snack between 9am-9:30am. At 9:30am, 
subjects will be taken to their bed, lie down and be given a pill (ZOL (5mg) or placebo) in a double-
blind fashion. We will be using 5mg in older adults, which is generally well tolerated in older adults 
(Langtry & Benfield, 1990). After ingesting the pill, subjects will be continuously monitored by study 
staff and allowed to nap for 2 hours. The two hour nap opportunity is being used in this study, contrary 
to the specification for treatment of insomnia suggested on the package insert suggesting a 6 hour 
time in bed. The reason for this discrepancy is that this is not a clinical treatment for insomnia but 
rather an investigation of the drug effects on the brain activty during a single cycle of sleep 
(approxminately 90-100minutes of sleep). Following their nap, subjects are allowed to watch TV, listen 
to music, read, etc. but must not nap or consume any caffeine or alcohol during this time. Lunch will be 
served, and subjects will be offered opportunities to stretch their legs accompanied by a research 
assistant. Subjects will have their blood pressure taken multiple times during their down time in the lab 
to make sure their blood pressure is not below or above the normal range. Following their observation, 
subjects will complete the word-pair associates task and finger tapping task from 7pm-8:30pm (test 
session 2).  At the end of the day, participants will go through gait testing to ensure that they are not 
feeling any residual effects from the medication. If participants are not experiencing adverse effects of 
drug, participants will be allowed to leave the lab. If participants report experiencing any adverse 
events or do not pass the gait examinations, they will remain in lab until symptom free. In addition, if 
during the experimental day the subject experiences an adverse event such as confusion, amnesia, 
ataxia, we will immediately terminate testing, and the on call doctor will be called. If no improvement is 
evident after a period of time set by the on-call doctor, we will call 911.  
 
Subjects will be asked to have someone drive them, or we will provide taxi service between the lab 
and home. 
 
2. Describe the duration of a subject’s participation in the study.  If there are sub-studies, include 
duration of participation in each sub-study. 
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Participants will be involved for about three weeks, but this time frame may be extended for scheduling 
purposes. Exact scheduling will depend on each individual subject’s personal schedule and 
availability. 
 
Each experimental day will require the subject to be available between 6:30AM and 9PM. Testing will 
occur between 7-8:30AM, and 7PM and 8:30PM, the nap will occur between 9:30AM and 11:30AM. 
3. List data collection instruments (e.g., measures, questionnaires, interview questions, observational 
tool, etc.).  
Investigator-authored, non-standardized, or un-validated measures must be submitted for 
review.      
Polysomnography: All in-lab sleep periods are PSG-recorded and include standard 
electroencephalographic (EEG), electro-oculographic (EOG), electromyographic (EMG), and 
electrocardiographic (ECG) measures for recording sleep. Electroencephalographic (EEG) sleep 
recording: The EASYCAP is comfortable to wear during wake and sleep recordings. Subjects will have 
their nap sleep recorded electroencephalographiclly with standard electroencephalographic (EEG), 
electro-oculographic (EOG), electromyographic (EMG), and electrocardiographic (ECG) measures. 32 
electrodes will be placed over the scalp using a conductive paste, after preparing the scalp area by 
light abrasion to reduce the scalp impedance. In this study, we will use EASYCAP GmbH from Brain 
Products with 32 sintered Ag/AgCl sensors, for their high signal quality and low steady electrode 
potentials. During wake the recorded event related potentials (ERPs) will be sampled at the rate of 500 
Hz and amplified using BrainAmp amplifier. The sampled ERPs will be transferred to the acquisition 
computer using USB2 adapter (BUA) for monitoring while recording EEG/ERPs and for further off-line 
analysis. The ERP signals will be recorded using an average reference (on-line reference) and will be 
re-referenced to the average of the left and right mastoids for off-line analysis. Eye movements and 
other artifacts will be removed manually from each data set. Naps will be conducted in the Psychology 
Building, rooms 2124A-E. Subjects will be monitored and their sleep minutes counted to ensure 
consistent sleep times for each group.  
 We will analyze minutes and percent in each sleep stage (i.e. Stage One, Stage Two, Slow Wave 
Sleep, and REM); total sleep time, wake after sleep onset, sleep latency, REM latency, and sleep 
efficiency; power spectral analysis of specific frequency bands associated with sleep (delta 0.3-4 Hz, 
theta 4-8 Hz, alpha 8-12 Hz, sigma 12-16 Hz); REM density (i.e., the frequency of rapid eye 
movements during REM sleep); phasic and tonic REM sleep (Ermis et al., 2010).  
 
EEG Electrode Maintenance: We use the standard procedure for cleaning and disinfecting our EEG 
electrodes that has been approved by the Board of Trustees of the American Society of 
Electroneurodiagnostic Technologists (ASET) and the Society for Psychophysiological Research’s 
(SPR) Ad Hoc Committee who compiled a report on guidelines for reducing the risk of disease 
transmission in the psychophysiological laboratory (Putman et al., 1992). 
 
The potential risk of infection for the surface electrodes used in the current proposal is of importance, 
as the electrodes come in contact with skin that has been purposely abraded with cleaning solution in 
order to reduce impedance levels. Importantly, little abrasion is needed to achieve optimal levels of 
impedance, and all products used to abrade the skin are sterile. 
The first step in handling the EEG equipment and contacting research participants is that all 
technicians wash hands before and after working with the research participant. Technicians wear 
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sterile, latex-free, surgical gloves during skin abrasion and cleaning, as well as during electrode 
preparation, application and removal. Gloves are disposed of after every use.  
Cleaning is accomplished before disinfection. We clean with warm water, and scrub gently with a soft 
brush. The electrodes are then dried with a soft cotton cloth. We disinfect the electrodes by soaking 
them for 15 minutes in Sekusept-Plus solution, a germicide used extensively in EEG labs and 
hospitals Glucoprotamin. This solution has broad spectrum microbial efficacy, is fast-acting and 
biodegradable. After disinfecting, the electrodes are rinsed using filtered water (i.e., drinking water 
quality). For drying, the electrodes are padded dry with a clean towel and then left to air dry.  Any 
defective electrodes will be discarded.  
Cognitive Tasks  
Word Pair Associates Task: In this task, subjects are visually presented with nonsense word pairs (e.g. 
table-disboon) to maximize the novel episodic and associative declarative memory demands of the 
task and minimize the semantic demands of the task (Otten et al., 2007). The second word is 
presented under the first word to avoid lateralization effects. Subjects are presented with 48 word-pairs 
in the morning session. Recognition tests are assessed both immediately following the encoding 
session, and delayed during retrieval sessions 1 and session 2. At test, participants are presented with 
40 intact word-pairs (minus the first and last four pairs to avoid primacy and recency effects), as well 
as 40 rearanged word-pairs (foils). Each word pair is displayed for 3000 ms followed by a response 
prompt asking for a discrimination of whether the two words were shown together as a pair in the study 
list. The discrimination is based on a standard 6-point confidence scale. 
 
Finger Tapping Task (FTT): In this task there will be 12 blocks (each 1 minute) in which participants 
will be asked to type a number sequence of 5 digits (e.g. 32451) as quickly and as accurately as 
possible. Participants will type for 30 seconds prior to having a 30 second rest period.  
 
Digit span Forward/Backward: In this task subjects are presented with a list of items and will be asked 
to repeat that with the same order or in reverse order. Items may include words, numbers or letters. 
 
Stroop task: In this task subjects are presented with the name of a color that is printed in a color not 
denoted by the name and they will be asked to name the color. 
 
Symbol digit: In this task subjects are presented with a list of digit-symbol pairs followed by a list of 
digits and will be asked to type the corresponding symbol under each digit as fast as possible. 
 
Survey testing: Participants may be asked to complete a variety of questionnaires throughout the 
study. Questionnaires administered will include: a) the Epworth Sleepiness Scale; b) Horne-Ostberg 
Morningness-Eveningnsess Questionnaire; c) Karolinska Sleepiness Scale; d) the Pittsburgh Sleep 
Quality Index; e) post-nap questionnaire; f) sleep inertia questionnaire; g) Spielberger State-Trait 
Anxiety Index; and h) the CES-D i) STOP BANG Questionnaire. Questionnaires will be administered 
online via a secure survey website (www.surveymonkey.com), and paper copies will be available in 
the lab in the event of loss of internet connection.  
 
Electroencephalographic (EEG) sleep recording: For sessions involving EEG recording, electrode 
caps will be attached following the EEG procedures described below. Participants in the nap condition 
will be allowed a two-hour nap opportunity to obtain either 60 or 90 minutes of total sleep time.  
 
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The SCID-5 interview is utilized as a screening tool and participant answers will be reviewed to 
determine their general psychological and psychiatric well being. Participant answers will only be used 
to determine eligibility for the current study. The SCID-5 will not be used as a formal diagnostic tool in 
the current protocol.  
 
Debriefing: At the end of the study, after all visits have been completed, subjects will be given the 
opportunity to ask any questions about the study and will be financially compensated. 
 
D. UCIMC Supplementary Clinical Services 
If a UCIMC clinical unit/department (e.g., phlebotomy for blood draws, pharmacy for dispensing study 
drug(s), radiation services for X-rays, MRIs, CT scans, and Neurology for lumbar punctures) will perform 
research-related procedures:  
1. List the research procedure (e.g. lumbar puncture, MRI, CT Scan), and  
2. Identify the unit/department that will perform the procedure. 
[   ] Not applicable: This study does not involve the services of a UCIMC clinical unit/department. 
1. This study will require drug dispensing and study blind set-up and maintenance by TRISHA MARIS 
(Hufnagel), Pharmacist Specialist at the Investigational Drug Services Pharmacy of UC Irvine 
Health (address: 101 The City Drive, Building #3, Room #211, Orange, CA 92868, Tel: 714-456-
7833/714-456-5911, thufnage@uci.edu) 
 
E. Privacy  
Privacy is about the subject’s ability to control how much others see, touch, or collect information about 
the subject.  Indicate all of the following methods that will be used to assure subject privacy. Violations 
of privacy include accessing a subject’s private information without consent, asking personal sensitive 
information in a public setting, being audio recorded or photographed without consent.   
[   ] Research procedures (including recruitment) are conducted in a private room. 
[   ] Use of drapes or other barriers for subjects who are required to disrobe. 
[   ] Only sensitive information directly related to the research is collected about subjects. 
[ x ] When information is collected from internet sources, the internet site’s privacy statement will be 
reviewed and followed.  
 Provide a copy of the Data Use Policy to the IRB. 
 
[   ] Other (specify): <Type here> 
 
F. Use of Existing Biological Specimens and/or Existing Information/Data 
1. For studies that involve use of existing (i.e. on the shelf; currently available) specimens: 
a. Indicate the source of the specimens and whether the specimens were originally collected for 
research purposes. 
b. Explain how the existing specimens will be obtained.  
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[ x ] Not applicable: This study does not involve use of existing biological specimens.   
Source: Indicate all that apply: 
[   ] UCI/UCIMC 
Originally collected for research purposes:    [   ] YES; UCI IRB number (i.e. HS#):  <Type here>      
            [   ] NO; explain: <Type here> 
 
[   ] UCIMC Pathology Biorepository will provide specimens. 
 
[   ] Non-UCI Entity; specify: <Type here> 
Originally collected for research purposes:    [   ] YES 
 Submit a copy of the IRB Approval Notice and 
Consent Form for the original collection.   
            [   ] NO; explain: <Type here> 
 
 [   ]  Other; explain:  <Type here> 
2. For studies that involve use of existing (i.e. on the shelf; currently available) clinical data: 
a. Specify the source of the clinical data. 
b. Explain how the study team will access the clinical data. Access to UCI Medical Center 
medical records for research purposes outside the capacity of the Honest Broker Services, 
such as access to physician notes, must be obtained from the Health Information Management 
Services.   
 For investigator initiated/authored studies only, submit a data abstraction sheet that includes a 
complete list of data elements/information that will be collected from (existing) records or submit the 
case report form (CRF; eCRF).   
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[  ] Not applicable: This study does not involve use of existing clinical data.  Skip to Section 6.G. 
Source: Indicate all that apply: 
[ x  ] UCI/UCIMC. 
[   ] non-UCI Entity; specify: <Type here> 
 
How Obtained: Indicate all that apply: 
[   ] The study team will request specific patient information/data from UCIMC Health Information 
Management Services. 
[  x ] The study team will review their patients’ records and abstract data directly from those records. 
[   ] The study team will request specific patient information/data from UCI Health Honest Broker 
Services.  Describe the following: 
Cohort selection criteria (e.g., use the available Clinical Terms from the Cohort Discovery Tool 
such as Demographics: Gender, Diagnoses: Asthma, Procedures: Operations on digestive 
system): <Type here> 
 
Expected cohort size/patient count: <Type here> 
 
Cohort attributes or data elements (e.g., lab test values, medication, etc.): <Type here> 
 
 [   ]  Other; explain:  <Type here> 
3. For studies that involve use of existing (i.e. on the shelf; currently available) clinical data, specify the 
time frame of the clinical data to be accessed (e.g. records from January 2002 to initial IRB 
approval).   
We will review subjects’ records immediately after the physician completes a medical history and 
physical form. 
 
G. Collection of Photographs, or Audio/Video Recording 
1. Describe all procedures involving the use and/or collection of photographs, or audio/video recording.  
[ x ] Not applicable: This study does not involve photographs or audio/video recording.  Skip to Section 
6.H. 
<Type here> 
2. Specify if photographs or audio/video recording will include subject identifiable information (e.g., 
name, facial image).  If so, indicate which identifiers will be collected. 
<Type here> 
3. Explain whether the photographs or audio/video recording will be included in subsequent 
presentations and/or publications and, if so, whether subject identifiers will be included.  
<Type here> 
 
H. Sharing Results with Subjects 
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1. Describe whether individual results (results of investigational diagnostic tests, genetic tests, or 
incidental findings) will be shared with subject or others (e.g., the subject’s primary care 
physician).  Only tests ordered by a physician and conducted in a CLIA certified lab may be 
shared.  
2. Explain what information will be shared and how the results will be shared.  
[ x ] Not applicable: Individual results will not be shared with subjects. 
<Type here> 
3. Describe whether overall study results will be shared with subjects.   
4. Explain how results will be shared. 
[ x] Not applicable: Final study results will not be shared with subjects. 
<Type here> 
 
I. 
     Statistical Considerations (This section is required for Investigator-Authored Research) 
1. Statistical Analysis Plan: Describe the statistical method(s) for the stated specific aims and 
hypotheses. 
 
The Biostatistics, Epidemiology and Research Design (BERD) Unit under the Institute for Clinical 
and Translational Science (ICTS) can assist in developing power and sample size calculation.  
Visit: http://www.icts.uci.edu/services/berd%20request.php for a consultation. 
 
Your analysis plans should match the stated study specific aims and hypotheses in Section 1. 
[   ] Not applicable: A statistical analysis plan is not appropriate for this qualitative study design. Plan 
for assessing study results: <Type here> 
Skip to Section 7. 
We hypothesize that older adults will show a dose-dependent increase in declarative associative 
verbal memory compared with placebo. In addition, we hypothesize that spindle density will increase in 
a dose-dependent manner, compared with placebo, and that performance will be correlated with 
spindle density.  
In the experimental nap, we will predict a dose-dependent increase in sleep spindle density in ZOL, , 
compared with placebo. We predict that spindle density will be modulated equally for fast and slow 
frequency spindles, and no differences in spindle amplitude, frequency, or duration between drug 
conditions. However, we predict that declarative verbal memory, but not motor learning, will be 
correlated with the density of fast frequency spindles, but not slow frequency spindles. That is, ZOL 
will increase the amount of normally occurring fast and slow spindles, not affect spindle morphology, 
and only fast spindles will correlate with performance. We will examine spindles in Stage 2 and SWS 
separately, and NREM (Stage 2 + SWS) sleep combined. We expect Stage 2 spindles and sigma 
power to be topographically dominant over the central electrodes and that spindles and sigma power 
in deeper NREM sleep will be concentrated in frontal electrode sites. As a negative control for 
spindles, we will examine slow oscillations and expect no differences across drug conditions. For sleep 
stages, we expect that there will be increased SWS in the ZOL condition compared with placebo. 
Furthermore, we predict dose-dependent decreases in REM sleep with ZOL, compared with placebo. 
ZOL will increase sleep efficiency by decreasing wake after sleep onset and sleep latency, compared 
with placebo. No differences between conditions in Stage 1, Stage 2 sleep, or Total Sleep Time (which 
will be held constant) are predicted.  
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2. Describe the primary statistical method(s) that will be used to analyze the primary outcome(s) or 
endpoints.  
We will employed repeated-measures anovas to examine differences in performance across drug 
conditions.  
Linear and hierarchical regressions will be used to assess the relationship between 
electrophysiological variables and memory performances, controlling for confounding factors such 
as age, BMI, anxiety and depression levels.  
 
3. Describe the secondary statistical method(s) that will be used to analyze the secondary 
outcome(s) or endpoints.  
 
4. If appropriate describe secondary or post hoc analyses of primary outcome(s) or other exploratory 
analysis. 
 
5. Sample Size Determination: Explain how the overall target sample size was determined (e.g., 
power analysis; precision estimation), providing justification of the effect size for the primary 
outcome based on preliminary data, current knowledge/literature and/or cost consideration; if 
appropriate, provide sample size justification for secondary outcomes. Power analysis should (at 
least) match the primary outcome/endpoint. 
Power Analyses: We have conducted power tests (Keppel, 1991) on the results obtained from our 
preliminary work as well as findings from the literature.  For example, the significant main effect of 
zolpidem on memory (a within-subjects design with 30 subjects) had 95% power with an eta 
squared effect size of 0.15 (us-ing α=.05). For older adults, a recent paper examining the effects 
of sleep on word pair learning in healthy older adults (a within-subjects design with 46 subjects; 
Wilson et al., 2012) reported 90% power with an R-squared effect size of 0.23  Based on these 
analyses we anticipate using minimum sample sizes of 45 subjects for the current study. 
 
SECTION 7: RISK ASSESSMENT AND POSSIBLE BENEFITS 
 
A. 
Risk Assessment 
1. Indicate the appropriate level of review of this study, based upon your risk assessment. 
[ x] This study involves greater than minimal risk to subjects and requires Full Committee review. Skip 
to Section 7.B. 
[   ] This study involves no more than minimal risk and qualifies as Expedited research.   
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2. If this study involves no more than minimal risk, provide justification for the level of review and for 
all applicable Expedited Categories you have chosen. 
<Type here> 
 
B.      Risks and Discomforts 
1. Describe and assess any reasonably foreseeable risks and discomforts — physical, psychological, 
social, legal or other.  Include an assessment of their expected frequency (e.g., common – 65%, less 
common – 40%, unlikely – 5%, rare - <1%) and the seriousness (mild, moderate, severe).  A bullet 
point list is recommended. If this study will involve the collection of identifiable private information, 
even temporarily, for which the disclosure of the data outside of the research could reasonably place 
the subjects at risk, include the risk of a potential breach of confidentiality. 
 
2. Discuss what steps have been taken and/or will be taken to prevent and minimize any risks/ 
potential discomforts to subjects.  Examples include: designing the study to make use of procedures 
involving less risk when appropriate; minimizing study procedures by taking advantage of clinical 
procedures conducted on the subjects; mitigating risks by planning special monitoring or conducting 
supportive inventions for the study; implement security provisions to protect confidential information. 
In older adults, zolpidem and other sleep aids have been shown to increase risks for falls. Due to the 
expanded age range of the subjects, we will take increased precautions in order to reduce this risk. 
These precautions include conducting the entire protocol under at the ICTS. In addition, during the 
naps a trained sleep technician will monitor the EMG throughout the nap for muscle movement and 
each subject will be closely attended throughout the study by a research assistant and nurse who will 
provide close monitoring and guidance for the subjects after drug administration and throughout the 
day.  For the most common side effects (i.e., nausea, vomiting headache), a discussion with the 
attending nurse and on-call doctor will occur to determine appropriate treatment (i.e., treated with an 
over-the-counter medication (e.g., ibuprofen), or the subject will be taken to the Health Services 
located on the UC Irvine campus for further treatment) per Risks section of the UCI Consent. 
 
For more serious events, 911 will be called and the study physician will be contacted immediately. Any 
medical care required as a result of study participation will be the financial responsibility of the 
researchers and will be provided to the participant at no cost to them or their third-party insurer. 
 
In the case of an emergency, study staff will call 911 immediately. In the event of a minor adverse 
event, medical aid will be enlisted in the following order: 1) Primary study physician), 2) Backup study 
physician); 3) Health Services for University-affiliated subjects or subject’s primary care provider. 
 
During the study, research staff will monitor subjects every 15 minutes while they are in the lab. Blood 
pressure and pulse will be collected before drug administration, as well as every hour after drug 
administration until nighttime sleep. 
 
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If a subject expresses a strong wish to discontinue the study, or has any major difficulty, the protocol 
will be discontinued. Research staff will have a list of phone numbers for use if questions or unusual 
events occur during the day or night. The research staff is experienced in monitoring subjects during 
these types of protocols.    
Adverse events, whether deemed related to drug administration or not, will be reported verbally to the 
UCI Office of Research within 24 hours and followed as soon as possible, but no later than 10 days, by 
a written report. 
 
All files with personal information will be kept in a locked file cabinet in a locked office and only people 
affiliated with this study will have access to the research records. All electronic data are de-identified 
and stored on password-protected computers. 
 
C. 
Potential Benefits 
1. Describe the potential benefits subjects may expect to receive from participation in this study.  
Compensation is not a benefit; do not include it in this section. 
[ x ] There is no direct benefit anticipated for the subjects. 
No tangible benefits to the participants are expected. 
2. Specify the expected potential societal/scientific benefit(s) of this study.   
Benefits to society at large include a better understanding of the role sleep has on memory 
consolidation.  This could lead to breakthrough treatments in a wide range of disorders as well as 
enhancement of normal cognition. The significance of this study rests on both the specific data to be 
collected and on the development of the experimental paradigm itself. With respect to the former, it is 
our ultimate aim to find a metric for implementing targeted naps for the specific behavioral needs of 
individuals. Previous work has shown sleep-stage-specific performance enhancements in well-rested 
subjects. Since real world situations involve either limited or no sleep, it becomes necessary to 
understand how naps can help integrate a wide variety of information under these circumstances. The 
knowledge derived from these data should be quickly amenable to direct transition field studies. 
Beyond this important contribution, though, the experimental paradigm itself holds much potential for 
addressing a variety of related questions. The experimental design allows for a consistent test of a 
variety of interventions that can occur throughout the day or night, in the context of any sleep and work 
schedule. Given the relatively minimal risks to participants involved and the potential benefits of 
understanding how daytime naps can improve memory and alertness, we believe the risk/benefit ratio 
is acceptable. 
 
SECTION 8: ALTERNATIVES TO PARTICIPATION 
 
Describe the alternatives to participation in the study available to prospective subjects. Include routine 
(standard of care) options as well as other experimental options, as applicable.  
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[ x ] No alternatives exist. The only alternative to study participation is not to participate in the study. 
[   ] There are routine standard of care alternatives available; specify: <Type here> 
[   ] There are other alternatives to study participation; specify: <Type here> 
 
SECTION 9: SUBJECT COSTS  
 
1. Indicate below if subjects or their insurers will be charged for study procedures. Identify and 
describe those costs.   
[   ] Not applicable: This study involves no interaction/intervention with research subjects. Skip to 
Section 10. 
[ x ] This study involves interaction/intervention with research subjects; however there are no costs to 
subjects/insurers. 
[   ] This study involves interaction/intervention with research subjects, and there are costs to 
subjects/insurers: <Type here> 
2. If subjects or their insurers will be responsible for study-related costs, explain why it is appropriate 
to charge those costs to the subjects or their insurers.  Provide supporting documentation as 
applicable (e.g., study procedures include routine (standard of care) procedures; FDA 
IDE/HDE/IND letter that supports billing to subjects). 
[ x ] Not applicable: The study involves no costs to subjects for study participation. 
[   ] Study related costs will be billed to subjects or their insurers for the following reasons: <Type 
here> 
 
SECTION 10: SUBJECT COMPENSATION AND REIMBURSEMENT 
 
1. If subjects will be compensated for their participation, explain the method/terms of payment (e.g., 
money; check; extra credit; gift certificate).  
[   ] Not applicable: This study involves no interaction/intervention with research subjects. Skip to 
Section 11. 
[   ] No compensation will be provided to subjects.   
[ x ] Compensation will be provided to subjects in the form of cash/gift certificate. 
[  ] Compensation will be provided to subjects in the form of a check issued to the subjects through the 
UCI Accounting Office. The subject’s name, address, and social security number, will be released 
to the UCI Accounting Office for the purpose of payment and for tax reporting to the Internal 
Revenue Service (IRS). 
[   ] Other:  <Type here> 
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2. Specify the schedule and amounts of compensation (e.g., at end of study; after each session/visit) 
including the total amount subjects can receive for completing the study.  Compensation should be 
offered on a prorated basis when the research involves multiple visits.  
 
For compensation ≥ $600, subject names and social security numbers must be collected. This 
information must be reported to UCI Accounting for tax-reporting purposes. 
[   ] Not applicable: This study involves no compensation to subjects. 
Subjects will be compensated with the following schedule and amounts: Participants will receive $300 
in the form of cash for their participation in this study. They will receive compensation upon completion 
of the study. Compensation is broken down as follows: $100 for each of the two nap experimental 
visits, $50 for the adaptation nap, and a $50 bonus for completing the study. If participants withdraw 
from the study before completion, the payment will be prorated based on the portion of the study they 
completed. They will not be compensated for only completing the initial interview or the medical 
examination. 
3.   Specify whether subjects will be reimbursed for out-of pocket expenses. If so, describe any 
requirements for reimbursement (e.g., receipt). 
[  ] Not applicable: This study involves no reimbursement to subjects. 
Subjects will be reimbursed; specify: Subjects will be reimbursed for costs of transportation. 
 
SECTION 11: CONFIDENTIALITY OF RESEARCH BIOSPECIMENS/DATA 
 
A. 
 Biospecimens/Data Storage 
1. Indicate all subject identifiers that may be included with the biospecimens or collected for the 
research study. If any study-related data will be derived from a medical record, added to a medical 
record, created or collected as part of health care, or used to make health care decisions the HIPAA 
policy applies. The subject’s HIPAA Research Authorization is required or a waiver of HIPAA 
Research Authorization must be requested by completing Appendix T. 
[   ] This study does not involve the collection of subject identifiers.  
Check all the following subject identifiers will be used, created, collected, disclosed as part of the 
research:   
[ x  ] Names  
[   ] Social Security Numbers  
   [   ] Device identifiers/Serial numbers 
[ x  ] Dates* 
[   ] Medical record numbers  
   [   ] Web URLs 
[ x  ] Postal address 
[   ] Health plan numbers                 [   ] IP address numbers 
[ x  ] Phone numbers 
[   ] Account numbers  
 
   [   ] Biometric identifiers 
[   ] Fax numbers 
[   ] License/Certificate numbers     [   ] Facial Photos/Images 
[ x  ] Email address 
[   ] Vehicle id numbers  
 
   [   ] Any other unique identifier 
[ x  ] Other (Specify all): Medical history and physical form that is completed by a physician will be 
shared with our research team.  
* birth date, treatment/hospitalization dates 
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Indicate how data will be stored and secured, including electronic data as well as hardcopy data paper 
records, electronic files, audio/video tapes, biospecimens, etc. If the research data includes subject 
identifiable data and/or Protected Health Information, the storage devices or the electronic research 
files must be encrypted.  [For guidance on the use of cloud services, please review the UCI OIT 
policy.] 
Electronic Data/Files (check all that apply): 
[   ] Anonymous data will be maintained; no subject identifiers 
[   ] Coded data; code key is kept separate from data in secure location. 
[   ] Data includes subject identifiable information.  Provide rationale for maintaining subject identifiable 
info): <Type here> 
[ x  ] Data will be stored on secure network server.  
[ x  ] Data will be stored on standalone desktop computer (not connected to network/internet) 
[   ] Other (specify here): <Type here> 
 
Hardcopy Data (Records, Recordings, Photographs) and Biospecimens (check all that apply): 
[   ] Anonymous biospecimens/data will be maintained; no subject identifiers 
[   ] Coded data; code key is kept separate from biospecimens/data in secure location. 
[ x  ] Biospecimens/Data includes subject identifiable information (Provide rationale for maintaining 
subject identifiable info): We will keep a hardcopy of identifiable information in the case we have to 
contact subjects after they complete their study. 
[ x  ] Data will be stored in locked file cabinet or locked room.  
[   ] Biospecimens will be stored in locked lab/refrigerator/freezer. 
[   ] Other (specify here): <Type here> 
2. List the location(s) where the data and/or biological specimens will be stored.  
Data will be stored at UCI Social Science Lab – Room 380. 
3. If subject identifiable data will be transported or maintained on portable devices, explain why it is 
necessary use these devices. Only the “minimum data necessary” should be stored on portable 
devices as these devices are particularly susceptible to loss or theft. If there is a necessity to use a 
portable device for the initial collection of identifiable private information, the research files must be 
encrypted, and subject identifiers transferred to a secure system as soon as possible.   
[  x ] Not applicable: Research data will not be transported or maintained on portable devices. 
Research data will need to be maintained on the following portable device(s) for the following 
reason(s): <Type here> 
 
B. 
Data and/or Biological Specimens Access 
Specify who will have access to subject identifiable data and/or biological specimens as part of this 
study. 
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[   ] Not applicable: No subject identifiers will be collected.  
[ x  ] Authorized UCI personnel such as the research team and appropriate institutional officials, the 
study sponsor or the sponsor’s agents (if applicable), and regulatory entities such as the Food and 
Drug Administration (FDA), the Office of Human Research Protections (OHRP), and the National 
Institutes of Health (NIH). 
[   ] Other:  <Type here> 
 
C. Data and/or Biological Specimens Retention    
Indicate how long subject identifiable data and/or biological specimens, including the subject code key 
will be retained. If more than one of the options below is applicable (e.g., the study involves children), 
records must be kept for the longer period. 
[   ] Not applicable: No subject identifiable research data will be retained.  
[   ] Separate code key will be destroyed or subject identifiable information will be removed from the 
biospecimens and/or data at the earliest convenience, consistent with the conduct of this research. 
Specify timeframe:  <Type here> 
[   ] Destroyed once research data is analyzed. 
[   ] Destroyed after publication/presentation. 
[   ] Will be maintained; specify time frame and provide the rationale: <Type here>   
[ x  ] Will be stored and maintained in a repository for future research purposes.  
Complete Appendix M  
[   ] Will be retained for six years as this research involves Protected Health Information (PHI) (e.g., IRB 
documentation, consent/assent forms – NOT the actual PHI).  Investigators must destroy PHI at the 
earliest opportunity, consistent with the conduct of this study, unless there is an appropriate 
justification for retaining the identifiers or as required by law. 
[   ] Will be retained for seven years after all children enrolled in the study reach the age of majority 
[age 18 in California] as this study includes children. 
 [   ] Will be retained 25 years after study closure as this study involves in vitro fertilization studies or 
research involving pregnant women.  
 [   ] Will be retained for two years after an approved marketing application, as this is a FDA regulated 
study. If approval is not received, the research records will be kept for 2 years after the investigation 
is discontinued and the FDA is notified. 
[   ] Other: <Type here> 
 
D.      Photographs, Audio/Video Recordings Retention 
1. If subject identifiable audio or video recordings will be collected, specify the timeframe for the 
transcription and describe retention/destruction plans.   
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[ x  ] Not applicable: Subject identifiable audio/video recordings will not be collected. 
[   ] Audio or video recordings transcribed; specify time frame:  <Type here> 
[   ] Audio or video recordings will be maintained; specify time frame:  <Type here> 
[   ] Audio or video recordings maintained indefinitely; provide the rationale:  <Type here> 
[   ] Audio or video recordings destroyed; specify time frame:  <Type here> 
2. If subject identifiable photographs will be collected, describe retention/destruction plans. 
[ x  ] Not applicable: Subject identifiable photographs will not be collected. 
[   ] Photographs will be maintained; specify time frame:  <Type here> 
[   ] Photographs maintained indefinitely; provide the rationale:  <Type here> 
[   ] Photographs destroyed; specify time frame:  <Type here> 
 
E. 
     Certificate of Confidentiality 
1. Indicate whether a Certificate of Confidentiality (COC) has been or will be requested.  
[  ] Not applicable: No COC has been requested for this study. 
[ x  ] A COC will be or has been requested for this study. The COC application must be submitted to 
the IRB staff for review after IRB approval. 
[   ] A COC has been obtained for this study. The expiration date of this COC is: <Type here> 
Provide a copy of the COC Approval Letter. 
2. Explain in what situations the UCI study team will disclose identifiable private information protected 
by a COC.   
The Certificate of Confidentiality does not prevent researchers from voluntarily disclosing information 
that would identify you as a participant in the research project as required by Federal, State or local 
laws, and with your consent, as necessary, for your medical treatment. This includes the disclosure of 
information that must be released to meet the requirements of the Food and Drug Administration 
(FDA). No voluntary disclosures will be made 
 
 
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