Chronic Insomnia and CSF Markers of Dementia
Conditions: Insomnia Chronic
Sponsor: University of Pennsylvania

Chronic Insomnia and CSF Markers of Dementia  
NCT# NCT04024020  
Document date: 11/15/2022 

Page 1 of 25
Continuing Review
Basic Info
Conﬁrmation Number:
dhbjifaj
Protocol Number:
829221
Created By:
GUNTER, PAUL
Principal Investigator:
GEHRMAN, PHILIP R
Protocol Title:
Chronic insomnia and CSF markers of dementia
Short Title:
Chronic insomnia and CSF markers of dementia
Protocol Description:
The goal of this project is to examine the relationship between chronic sleep disturbance 
(insomnia) and dementia biomarkers and orexin levels as assessed in cerebrospinal ﬂuid (CSF). 
Fifteen adults age 30-50 with chronic insomnia and age- and gender-matched good sleepers will 
undergo overnight polysomnography and morning CSF sampling.
Submission Type:
Biomedical Research
Application Type:
FULL
PennERA Protocol Status
Approved
Level of IRB Review Required
Convened Full Board Review
The following documents are currently attached to this item:
There are no documents attached for this item.
Summary of protocol modiﬁcations approved since last continuing review
Please provide a description of changes which have been reviewed and approved by the IRB since the 
last continuing review.
Subject Enrollment
Target subject enrollment at Penn
0
Target enrollment at other centers (multi-center study)
0
Number of subjects enrolled at Penn since the study was initiated
0
Actual enrollment at participating centers
0
Number of subjects enrolled at Penn since the last continuing review

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Total number of subjects who provided consent
0
Number of subjects determined to be ineligible
0
Number of subjects currently active/on study
0
Number of subjects lost to follow-up
0
Number of subjects no longer participating for other reasons
0
Number of subjects who have completed the study
0
Number of subjects who have withdrawn from the study
0
Race:
American Indian or Alaskan Native
0
Asian
0
Black or African American
0
Native Hawaiian or Paciﬁc Islander
0
White
0
Other
0
Unknown or Not Reported
0

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Ethnicity:
Hispanic or Latino
0
Not Hispanic or Latino
0
Gender
Male
0
Female
0
Other
0
Unknown / Not Reported
0
Total
0
Vulnerable Populations
Has your study enrolled pregnant woman?*
No
Has your study enrolled prisoners?*
No
Has your study enrolled children?*
No
Subject Withdrawal
How many subject voluntarily withdrew from the study?
0
How many subjects were withdrawn from the study at the request of the PI/Co-PI?
0
Number of subjects withdrawn due to adverse events/unanticipated problems
0
Subject withdraw reason*
If subjects voluntarily withdrew or were withdrawn, please indicate the reasons.

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Issues with recruitment/retention, informed consent, or other issues
If applicable, please provide a brief summary of any difﬁculty you experienced obtaining/retaining 
subjects or obtaining informed consent during the entire approval period. Additionally, please indicate if 
there have been any complaints about the research.
Informed Consent Process*
Recognizing that informed consent encompasses much more than a form or document there are a 
number of methods employed to educate a potential subject as to what is involved in a particular 
research project. The forms used are one method for documenting the informed consent process.Is 
written informed consent required for this project?
No
Is written HIPAA authorization required?*
No
New Findings
Signiﬁcant preliminary observations/interim ﬁndings
Have there been any signiﬁcant preliminary observations/interim ﬁndings during the past approval 
period. If yes, please describe below.
DMC or DSMB exists*
Does a data monitoring committee (DMC) or data and safety monitoring board (DSMB) exist?
No
DMC or DMB Report Status
The following documents are currently attached to this item:
There are no documents attached for this item.
Multi-site trial summary
If this study is a multi-site trial, provide a narrative summary of any relevant reports that have been 
received in the past year, regardless of whether the report has been previously submitted to the IRB.
Disclosure of Signiﬁcant Financial Interests*
Investigators (persons responsible for the design, conduct or reporting of this research protocol) must 
disclose any of the following ﬁnancial interests / relationships with any entity that sponsors, provides 
support, or otherwise has a ﬁnancial interest in the conduct or outcome of this research protocol 
(Outside Organization): Payments received for the past 12 months from a publicly traded Outside 
Organization for personal services (e.g., consulting, lecturing / speaking, service on the Scientiﬁc 
Advisory Board) plus the value of any current equity that when aggregated exceeds $5,000Payments 
received for the past 12 months from a non-publicly traded Outside Organization for personal services 
that in total exceed $5,000, or having any equity interestMembership on the governing board of any 
Outside Organization, including service on its board of directors, or having a position of authority or 
responsibility to act in its best interests, including being an ofﬁcer, manager, partner, or limited liability 
company member with management responsibilityInvestigators must also disclose any ﬁnancial interest 
in a drug, device or other product or a competing product (IP rights), regardless of whether the IP has 
been patented, licensed, or assigned to the Penn, if such IP is being tested, evaluated, or developed in, 
or if its commercial value could be affected by, this protocol.Investigators are not required to disclose 
equity in mutual funds and retirement accounts, as long as the Investigator does not directly control the 
investment decisions made in these vehicles.Does any Investigator (or his or her spouse or dependent 
children) have a SIGNIFICANT FINANCIAL INTEREST, as deﬁned above?
No

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If "YES", was this Financial Interest previously reported to the Conﬂicts of Interest Standing 
Committee?
Not Applicable
If "YES", has there been a change regarding this Financial Interest from what was previously 
reported to the Conﬂicts of Interest Standing Committee?
Not Applicable
The following documents are currently attached to this item:
There are no documents attached for this item.
Penn Intellectual Property*
To the best of the Principal Investigator's knowledge, does this protocol involve the testing, 
development or evaluation of a drug, device, product, or other type of intellectual property (IP) that is 
owned by or assigned to the University of Pennsylvania? Please refer to the Patent and Tangible 
Research Property Policies and Procedures.
No
Certiﬁcation
I have reviewed the Financial Disclosure and Presumptively Prohibited Conﬂicts for Faculty 
Participating in Clinical Trials and the Financial Disclosure Policy for Research and Sponsored Projects 
with all persons who are responsible for the design, conduct, or reporting of this research; and all 
required Disclosures have been attached to this application.
Yes
Study Completion / Expiration
Study Complete*
Is this study complete?
No
Study Complete - Explanation
If study is completePlease indicate why (eg., research related activities and data analysis are complete, 
required number of subjects reached, issues with protocol safety,etc.)
The following documents are currently attached to this item:
There are no documents attached for this item.
IRB Approval Expired*
Has IRB approval for this protocol expired or will it expire before the scheduled IRB review?
No
Research During IRB Approval Lapse
If the IRB approval for the protocol has expired or will expire before the scheduled IRB review, conﬁrm 
that no research related activities occurred/will occur without approval from the IRB unless the PI 
contacted the Ofﬁce of Regulatory Affairs and the IRB Executive Chair (or authorized designee) 
determined that it is in the best interest of subjects to continue during the lapse in IRB approval. For 
example, in a clinical trial there are (1) subjects who are enrolled but not on intervention, (2) subjects 
who are on intervention, and (3) subjects who have completed the intervention phase and are in follow 
up. The IRB Executive Chair must evaluate each of these groups separately regarding continuation of 
participation in the research after IRB approval has expired.Have any research activities occurred, or 
will any research activities need to occur, during the lapse in IRB approval?
No
Unanticipated Problems*
Since the last IRB Review, have there been any unanticipated study related events that have not been 

Page 6 of 25
previously reported to the IRB? If No, do not include these events with this submission. Refer to 
www.upenn.edu/regulatoryaffairs/index.php?option=com_content&task=view&id=16&Itemid=8
No
The following documents are currently attached to this item:
There are no documents attached for this item.
Adverse Events*
Since the last IRB review, has the proﬁle of adverse events (in terms of frequency, severity, or 
speciﬁcity) changed from previous experience or as documented in the research protocol, informed 
consent document, or investigator's brochure?
No
The following documents are currently attached to this item:
There are no documents attached for this item.
Documents attached from the IRB protocol application.
The following documents are currently attached to this item:
Full sponsor's protocol (csfprotocol.pdf)
Informed consent form (consent_1sep2022.pdf)
Additional Document (csf_cr_coverletter_29sep2022.doc)
List of Documents Details
Please detail the rationale for why any of the above documents are not attached to the submission (i.e. 
No Investigator's Brochure, Protocol, or Consent Forms are utilized for this protocol).

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Protocol Details
Resubmission*
Yes
Hospital Sites
Will any research activities and/or services be conducted at a Penn Medicine afﬁliated hospital site?
Yes
Active Hospital Sites
Hospital of the University of Pennsylvania (HUP) ***Primary***
Study Personnel
Principal Investigator
Name:
GEHRMAN, PHILIP R
Dept / School / Div:
10261 - PS-Affective Disorders Program
Campus Address
Mail Code
6021
Address:
U of PA Dept. of Psychiatry
3535 Market Street, Suite 670
City State Zip:
PHILADELPHIA PA 19104-3309
Phone:
215-746-3578
Fax:
215-573-0759
Pager:
Email:
philip.gehrman@pennmedicine.upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
GCP Training Completed:
Yes
Training Expiration Date:
05/17/2022
Name of course completed :
Good Clinical Practice: An Introduction to ICH (GCP) Guidelines

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Study Contacts
Name:
BARILLA, HOLLY
Dept / School / Div:
10261 - PS-Affective Disorders Program
Campus Address
Mail Code
3309
Address:
3535 MARKET
Suite 670
City State Zip:
PHILADELPHIA  PA 19104-3309
Phone:
215-746-4384
Fax:
-
Pager:
Email:
hbarilla@upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
GCP Training Completed:
Yes
Training Expiration Date:
06/14/2024
Name of course completed :
Good Clinical Practice: An Introduction to ICH (GCP) Guidelines
Name:
KAUTZMANN, JEREMIE
Dept / School / Div:
2100 - Health System
Campus Address
Mail Code
Address:
Clinical Practices of University of Pennsylvania
Psychiatry Admin
City State Zip:
Phone:
Fax:
Pager:
Email:
Jeremie.Kautzmann@Pennmedicine.upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
GCP Training Completed:
Yes
Training Expiration Date:
11/08/2024
Name of course completed :
Penn CR: Full Onboarding: Good Clinical Practice: An Introduction to ICH GCP Guidelines (2HRS)
Other Investigator
None
Responsible Org (Department/School/Division):
10261 - PS-Affective Disorders Program

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Key Study Personnel
Name:
RAIZEN, DAVID M
Department/School/Division:
NE-Neurology
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
GCP Training Completed:
No
Training Expiration Date:
Name of course completed:
Name:
GOONERATNE, NALAKA
Department/School/Division:
DM-Geriatrics
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
POR Recertiﬁcation Quiz - Full Board Review - SOM
GCP Training Completed:
Yes
Training Expiration Date:
01/21/2024
Name of course completed:
Good Clinical Practice (GCP) for the Experienced Investigator - OCR
Name:
FINDLEY, JAMES C
Department/School/Division:
DM-Sleep Medicine
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
GCP Training Completed:
No
Training Expiration Date:
Name of course completed:
Disclosure of Signiﬁcant Financial Interests*
Does any person who is responsible for the design, conduct, or reporting of this research protocol have 
a FINANCIAL INTEREST?
No
Penn Intellectual Property*
To the best of the Principal Investigator's knowledge, does this protocol involve the testing, 
development or evaluation of a drug, device, product, or other type of intellectual property (IP) that is 
owned by or assigned to the University of Pennsylvania? Please refer to the Patent and Tangible 
Research Property Policies and Procedures.
No
Certiﬁcation
I have reviewed the Financial Disclosure and Presumptively Prohibited Conﬂicts for Faculty 
Participating in Clinical Trials and the Financial Disclosure Policy for Research and Sponsored 
Projects  with all persons who are responsible for the design, conduct, or reporting of this research; and 
all required Disclosures have been attached to this application.
Yes
The following documents are currently attached to this item:
There are no documents attached for this item.

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Biomedical Research
Clinical Trial*
Is this a clinical trial? Please note the following deﬁnition:Clinical trial is deﬁned as a research study in 
which one or more human subjects are prospectively assigned to one or more interventions (which may 
include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral 
health-related outcomes. See CFR 45.46.102(b)
No
Investigator Initiated Trial*
Is this an investigator initiated trial? Please select "Yes" if ALL the following conditions are met:The 
research is subject to FDA regulations for human subjects research.The individual PI both initiates 
(plans and designs) and conducts an investigation and under whose immediate direction the 
investigational agent is administered or dispensed. The individual investigator has absolute 
responsibility and accountability and designs, conducts, monitors, manages the data, prepares reports 
and oversees all regulatory and ethical matters. See 21 CFR 312.3
No
Drugs or Devices*
Does this research study involve Drugs or Devices?
No
IND Exemption
For studies that fall under an IND exemption, please provide the number below
For studies including IND or IDE's, please provide the number(s) below
IDE Review*
NOTE: For research involving investigational devices, you are required to review the guidance on 
Managing Research Device Inventory. Consult the Penn Manual for Clinical Research: https://
www.med.upenn.edu/pennmanual/secure/investigational-product-management-at-sites-not-using-
investigational-drug-services-(ids).html Please check the box Yes if you have reviewed the guidance.
Yes
Research Device Management*
Please indicate how research device(s) will be managed.
Not Applicable (no investigational devices)
Drug, Herbal Product or Other Chemical Element Management *
Please indicate how drugs, herbal products or other chemical entities will be managed.
Not Applicable (no drugs, herbal products or other chemical entities)
Radiation Exposure*
Are research subjects receiving any radiation exposure solely because they are enrolled in this protocol? 
(e.g. X-rays, CT, Fluoroscopy, DEXA, pQCT, FDG, Tc-99m, etc.)?IF YES, the protocol must be 
approved by the RRSC (Radiation Research Safety Committee). Consult EHRS web site: 
www.ehrs.upenn.edu/protocols/radiohuman.html for more information.If you have questions, email 
jjesik@ehrs.upenn.edu or kavyap@upenn.eduIf your protocol includes Nuclear Medicine Procedures, 
the protocol must be reviewed by the Nuclear Med Operations Committee: https://redcap.link/NMOPS
No
Human Gene Therapy, Human Gene Transfer, Human Gene Editing*
Does this research involve the administration of any of the following to human subjects? Please consult 
your investigator's brochure, as needed. Recombinant or synthetic DNA or RNA (r-s-NA); Genetically 
modiﬁed Biologics (e.g., CAR T Cells) or Biosimilars; Recombinant or genetically modiﬁed:infectious 
organisms (e.g., Listeria),established cell lines, viral vectors, agents/products; Non-biologic vectors/
transfer agents delivering any of the above for a clinical trial; Use of novel gene editing approaches 
(e.g., CRISPR/Cas9, PRIME)IF YES, the study protocol and attendant materials must be registered in 
PIERS (Penn IBC Electronic Registration System) and reviewed by the Institutional Biosafety 

Page 11 of 25
Committee (IBC). Consult the EHRS website: https://ehrs.upenn.edu/health-safety/biosafety/
institutional-biosafety-committee-ibc. If you have questions, contact the Penn Institutional Biosafety 
Committee at 215-898-4453 (number subject to change) or contact the Institutional Biosafety Ofﬁcer 
(cell: 215-651-0546 or email: amaks@upenn.edu) The protocol may also require review by the Human 
Research Advisory Committee (HRAC). The IRB will notify the PI and study staff if this review is 
warranted. For new protocols requiring IBC registration and review, IRB approval cannot be granted 
until IBC approval is granted. Enrollment for a clinical trial cannot be initiated before obtaining IRB 
and IBC approvals.For new protocols requiring HRAC review, IRB approval cannot be granted until 
HRAC approval is granted.
No
Human Source Material*
Does this research include collection or use of human source material (i.e., human blood, blood 
products, tissues or body ﬂuids)? IF YES, consult the EHRS web site: www.ehrs.upenn.edu/programs/
bio/bbpathogens.html for information on OSHA Bloodborne Pathogens requirements (training, 
vaccination, work practices and Exposure Control Plan). If you have questions, call 215-898-4453. 
Yes
Image Guided Biopsies*
Does the research involve imaging guided biopsy? IF YES, please contact the Clinical Imaging Core. 
See https://www.med.upenn.edu/cbi for more details. Any questions should be directed to the Director 
of Research Operations, Dept of Radiology, Kathleen Thomas. 
No
Computerized Tomography (CT) Studies*
Does the protocol involve CT scans that are not considered standard of care and are being performed for 
research purposes?IF YES, complete the CACTIS Committee Application: https://is.gd/CACTIS and 
consult CACTIS website: http://www.uphs.upenn.edu/radiology/research/labs/cactis/ for application 
requirements.
No
CAMRIS and MRI Studies*
Is an MRI scan being performed for research only and NOT considered standard of care (example: 
speciﬁc scanner, parameters or solely for the purposes of research)?NOTE: Research/non-standard use 
of MRI may include but is not limited to any of the following: Situations in which MRI results may 
impact subjects current clinical care plan or treatment decisions, such as:The study requires a 
customized report with speciﬁcs regarding the study protocol (i.e., speciﬁc measurements or details); 
Introduction of a device of any kind during the MRI that is not used during a 'standard of care' type 
scan.Your MRI is not consistent with standard care time points for MRI imaging.Your MRI is not paid 
for by insurance.IF YES, consult CAMRIS website: https://www.med.upenn.edu/camris/application-
and-faq.html for application requirements and required institutional consent form language.
No
Investigational Agent or Device within the Operating Room*
Does the research project involve the use of an investigational agent or device within the Operating 
Room?
No
Cancer Related research not being conducted by an NCI cooperative group*
Does this protocol involve cancer-related studies in any of the following categories? Therapeutic, 
Prevention, Supportive Care, Screening, Early Detection, or Diagnostic, Epidemiologic, Observational, 
Outcome, Ancillary or Correlative. For a description of these categories, see http://www.ctsrmc.org/
submitting_a_protocol.php NCI Cooperative Groups are as follows:Alliance for Clinical Trials in 
OncologyNCI Clinical Trials Group (Canadian Cancer Society) (NCCTG)Children's Oncology Group 
(COG)NRG Oncology GroupECOG-ACRIN Cancer Research GroupSouthwest Oncology Group 
(SWOG) IF YES, the protocol must be submitted to the Cancer Center's Clinical Trials Scientiﬁc 
Review Committee for scientiﬁc review and approval prior to obtaining IRB approval. Consult the 
CTSRMC website: www.ctsrmc.org for application requirements 
No

Page 12 of 25
Processing of Materials*
Will the research involve processing (such as over encapsulating, or compounding)?
No
In-House Manufacturing of Materials*
Will the research involve processing (such as over encapsulating, or compounding)?
No
HIPAA / Protected Health Information
Does the research proposal involve accessing (viewing / using), collecting, or disclosing of protected 
health information (PHI) directly from participants or their medical or dental record for research 
purposes?
Yes
Indicate which item is provided with this submission:
Modiﬁed research informed consent document that incorporates HIPAA requirements
Cohort/data analysis tools used
Remote Study Visits
Does the research proposal involve conducting research visits remotely via any type of video 
conferencing software?
No
Remote Study Visits
Does the research proposal involve conducting research visits remotely via any type of video 
conferencing software?
No
CHPS Resources*
Does the research involve CHPS resources?
Yes
HUP Inpatient Nursing Resources
Does this research include an inpatient admission at HUP?
No
Pathology and Laboratory Medicine Resources*
Will samples be collected by hospital phlebotomy and/or processed or analyzed by any of the clinical 
laboratories of the University of Pennsylvania Health System?
No
Research Involves Apheresis, Cell Collection, and/or Blood Product Collection*
Does this research involve collection of blood products in the Penn Donor Center and/or the use of 
apheresis for treatment or collection of cells or other blood components?
No
Research involving blood transfusion or drug infusions*
Will your research involve blood transfusion or infusion of study drug in 3 Ravdin Apheresis Unit for 
research purposes?
No
HUP Perioperative and Procedural Services *
Does the research require the following: The collection of tissue, ﬂuid, or blood in HUP Perioperative 
and Procedural Services&emsp;ORThe administration of medications in HUP Perioperative and 
Procedural Services?This is inclusive to all phases of Perioperative care: pre-operative, intraoperative, 
and postoperative periods in all HUP Perioperative Procedure locations.If you have questions, please 
contact: HUPPeriopClinicalResearch@PennMedicine.upenn.edu
N/A

Page 13 of 25
Trial in Radiation Oncology
Is this research a prospective trial being done in Radiation Oncology, and if so, has this protocol been 
approved by the Radiation Oncology Protocol committee?
N/A
Study in Radiation Oncology
Is this research a retrospective study being done in Radiation Oncology, and if so, has this project been 
reviewed by the Radiation Oncology Clinical Research Group?
N/A
Use of UPHS services*
Does your study require the use of University of Pennsylvania Health System (UPHS) services, tests or 
procedures , whether considered routine care or strictly for research purposes? (UPHS includes all Penn 
hospitals and clinical practices, including the Clinical Care Associates network of community 
practices). Examples of UPHS services/tests/procedures includes the Clinical Translational Research 
Center (CTRC), laboratory tests, use of the pathology lab, cardiovascular imaging tests or radiology 
imaging tests (whether being billed via the Service Center or through UPHS), other diagnostic tests & 
procedures and associated professional services, etc. 
No
Veteran's Affairs (VA) Patients or Subjects
Does your study involve data from Veteran's Affairs (VA) patients or subjects?
No
If yes, was this approved by the Philadelphia VA?
No
Out of State Research
Will any Penn personnel conduct any research activities outside of the State of Pennsylvania?
No
Research involving Virtua Health
Will any Penn personnel conduct any research activities at a Virtua Health site location, OR in 
collaboration with Virtua Health System personnel, OR using any Virtua Health System resources (e.g., 
medical records)?
No
Artiﬁcial Intelligence Technology*
No
Human Stem Cells*
No
Primary Focus*
Mechanistic or physiologic study in human subjects (T1 Translational research in humans or Phase I 
drug research)

Page 14 of 25
Protocol Interventions
x Sociobehavioral (i.e. cognitive or behavioral therapy)
Drug
Device - therapeutic
Device - diagnostic (assessing a device for sensitivity or speciﬁcity in disease diagnosis)
Surgical
x Diagnostic test/procedure (research-related diagnostic test or procedure)
x Obtaining human tissue for basic research or biospecimen bank
x Survey instrument
None of the above
The following documents are currently attached to this item:
There are no documents attached for this item.
Sponsors
Business Administrator
Name:
CASTELLANO, DANIEL
Dept / School / Div:
4412 - PS-Psychiatry
Phone:
215-573-5833
Fax:
215-573-6410
Pager:
Email:
dcastel2@pennmedicine.upenn.edu
Department budget code
000 - 000 - 0 - 000000 - 0000 - 0000 - 0000
Funding Sponsors
Name:
MERCK & CO., INC.
Type:
UPENN Commercial/Industrial
Funding sponsors billing address
If you have selected a commercial or industry sponsor, please provide the appropriate address and 
contact information for the Sponsor for the purposes of billing for IRB review fees (initial review, 
continuing review and convened modiﬁcation fees apply here). If the Sponsor is not industry/
commercial, this information is not necessary to provide with your application.
Funding sponsors gift
Is this research being funded by a philanthropic gift?
No
Regulatory Sponsor
IND/IDE Sponsor
none

Page 15 of 25
000 - 000 - 0 - 000000 - 0000 - 0000 - 0000
Industry Sponsor
None
Project Funding*
Is this project funded by or associated with a grant or contract?
Yes
Selected Proposals
Proposal No
Title
10063203
Chronic Insomnia and CSF Markers of Dementia
Sponsor Funding
Is this study funded by an industry sponsor?
Yes
Status of contract
Complete
The following documents are currently attached to this item:
There are no documents attached for this item.
Multi-Center Research
Penn as lead
1. Is this a multi-center study where Penn is serving as the Lead Site or the Penn PI is serving as the 
Lead Investigator? 
No
Management of Information for Multi-Center Research
Penn irb of record
2. Is this a multi-center study where the Penn IRB will be asked to serve as the IRB of Record for other 
external study sites? 
No
Other Sites
No other sites
Protocol
Abstract
The longstanding view has been that insomnia, and other forms of sleep disturbance, emerge as a 
consequence of dementia and are the result of progressive neuronal damage. However, there is growing 
evidence that the direction of causation may go both ways, with sleep disturbance potentially increasing 
vulnerability to dementia. Longitudinal studies have found that sleep disturbance often precedes and 
increases risk for dementia by several years.The purpose of this study is to examine the relationship 

Page 16 of 25
between chronic insomnia and dementia biomarkers and orexin levels found in cerebrospinal ﬂuid 
(CSF). Fifteen adults age 30-50 with chronic insomnia and age- and gender-matched good sleepers will 
undergo overnight polysomnography and CSF sampling in the morning.
Objectives
Overall objectives
Patients with dementia very frequently have disturbed sleep that is thought to be caused, in part, by the 
dementing illness. There is growing evidence of the reverse direction of causation, with sleep 
disturbance increasing vulnerability to dementia. The recently-discovered glymphatic system, by which 
waste from neural metabolism is cleared from the brain, may be a mechanism for the sleep-dementia 
link. The goal of this project is to examine the relationship between chronic sleep disturbance 
(insomnia) and dementia biomarkers and orexin levels as assessed in cerebrospinal ﬂuid (CSF). Fifteen 
adults age 30-50 with chronic insomnia and age- and gender-matched good sleepers will undergo 
overnight polysomnography and morning CSF sampling.  These data will be used to address the 
following speciﬁc aims:  Speciﬁc Aim 1: To examine the association between chronic insomnia and 
CSF markers of dementia. Hypothesis 1: Chronic insomnia will be associated with higher levels of CSF 
AB markers compared to good sleepers.  Speciﬁc Aim 2 (exploratory): To examine the role of orexin in 
mediating the relationship between chronic insomnia and CSF markers of dementia. Hypothesis 2: 
Higher CSF orexin levels will mediate the relationship between chronic insomnia and A markers.
Primary outcome variable(s)
Dementia biomarkers in cerebrospinal ﬂuid
Secondary outcome variable(s)
CSF orexin levels
Background
Patients with Alzheimers dementia frequently experience sleep disturbance that gradual worsens with 
increasing severity of the disorder. For caregivers, having a patient with dementia awake during the 
night is one of the primary reasons cited for nursing home placement. The longstanding view has been 
that insomnia, and other forms of sleep disturbance, emerge as a consequence of dementia and are the 
result of progressive neuronal damage. For example, Alzheimers dementia has been shown to target the 
suprachiasmatic nucleus, the master clock of the body.  There is growing evidence that the direction of 
causation may go both ways, with sleep disturbance potentially increasing vulnerability to dementia. 
Longitudinal studies have found that sleep disturbance often precedes and increases risk for dementia 
by several years. In older adults without cognitive impairment, self-reported insomnia has been found to 
be associated with greater beta amyloid burden as assessed with PET imaging. One mechanism that 
could explain this relationship is the recently-discovered glymphatic system, through which potentially 
toxic byproducts of neural metabolism, such as A, are cleared from the nervous system. Metabolic 
solutes are excreted into the interstitial ﬂuid, which then ﬂow through interstitial space and pass into 
cerebrospinal ﬂuid (CSF) for clearance. During sleep, the interstitial space increases by 60%, allowing 
greater transport of metabolites. Acute sleep deprivation in mice leads to an increase in A levels in CSF. 
These studies demonstrate that disturbed sleep increases markers of Alzheimers disease and may 
increase vulnerability to the disorder. While the mechanisms underlying the glymphatic system are still 
under investigation, there is increasing evidence that the peptide orexin plays a crucial role. In humans, 
high CSF concentration of orexin-A was associated with increased phosphorylated tau. In an animal 
model of Alzheimers disease, genetic deletion of orexin led to only moderate increases in sleep duration 
but strongly suppressed the formation of amyloid plaques. In a second study of this mouse model, 
delivery of an orexin antagonist signiﬁcantly inhibited amyloid plaque formation. There is a need to 
better understand the role that orexin plays in the link between insomnia and Alzheimers disease.  Much 
of the literature in this area utilizes models of acute sleep disturbance, usually total sleep deprivation. 
Less is known about the impact of chronic sleep disturbance as it occurs in the general population, most 
notably in the form of chronic insomnia. Given that AB levels accumulate for up to years prior to the 
onset of dementia, improved understanding of the mechanisms through which deposition occurs could 
dramatically shift the landscape from treatment of dementia to one of prevention in two ways. First, 
promotion of good sleep throughout the lifespan may decrease vulnerability to dementia. Second, sleep 
research may provide a window into the physiology of the glymphatic system and lead to novel insights 
for non-sleep approaches for prevention and treatment. Given the commercial availability of an FDA-
approved orexin antagonist, there may be tremendous opportunity to decrease risk for dementia through 

Page 17 of 25
the treatment of chronic insomnia.
Study Design
Phase*
Not applicable
Design
Laboratory Observational study
Study duration
The total duration of the study will be 24 months, each participants duration in the study will be 
approximately 4 weeks.
Resources necessary for human research protection
Describe research staff and justify that the staff are adequate in number and qualiﬁcations to conduct 
the research. Describe how you will ensure that all staff assisting with the research are adequately 
informed about the protocol and their research related duties. Please allow adequate time for the 
researchers to conduct and complete the research. Please conﬁrm that there are adequate facilities for 
the research.
The principal investigator involved in this project has extensive experience in sleep research, including 
having a history of success in conducting studies with CSF sampling. A study coordinator will be hired 
for this study and they will be trained in all designated duties and responsibilities of the study. Philip 
Gehrman will provide oversight of the study coordinator. The study will be conducted at the CTRC, 
where there are sufﬁcient facilities and resources available.
Characteristics of the Study Population
Target population
Fifteen adults age 30-60 with chronic insomnia and ﬁfteen age- and gender-matched good sleepers.
Subjects enrolled by Penn Researchers
30
Subjects enrolled by Collaborating Researchers
0
Accrual
Participants will be recruited through targeted advertisements in the Philadelphia area community. We 
have a track record of success in recruitment through these approaches. To estimate the appropriate 
sample sizes, statistical calculations were carried out using pilot data obtained from OxA and ABO 
measurements from N=6 individuals. Speciﬁcally, two-sided two-sample t-test was utilized for a two-
group parallel design study which compared chronic insomniacs with good sleepers. For OxA, sample 
sizes needed to detect intended effect sizes (differences of 30%, 40%, and 50) were estimated at 80% 
power. For ABO, sample sizes were calculated to signiﬁcantly detect the differences between two 
groups of 50%, 100%, and 150% at 80% power. Power calculations were performed on OxA and ABO 
in raw and natural log scales, respectively, after examining the normality of data with residual plots. 
Variability estimates at each time point were obtained as averages of sample standard deviations of two 
treatment groups per time point.  As such, N=15/group would be sufﬁcient to identify changes in the 8 
AM samples considering effect sizes equal or greater than 30% and 100% for OxA and ABO, 
respectively.
Key inclusion criteria
All subjects must meet the following criteria: -Age 30-60 -Men and women To be included in the 
insomnia group, subjects must meet the following DSM5 Diagnostic Criteria for insomnia disorder: -
dissatisfaction with sleep quantity or quality (difﬁculty initiating or maintaining sleep, or waking up too 
early) despite adequate opportunity for sleep  -sleep disturbance causes clinical signiﬁcant distress or 
impairment in functioning  -present at least 3 times per week for at least 3 months  -sleep disturbance is 

Page 18 of 25
not better explained by a medical or psychiatric condition or based on the effects of a substance -
Insomnia Severity Index (ISI) score 14 or greater.
Key exclusion criteria
-Diagnosis or evidence of sleep disorders other than insomnia as determined by the screening 
questionnaires and clinical history -Women who have been pregnant or lactating within the past six 
months -Non-ﬂuency in spoken or written English -Current or past month shiftwork deﬁned as working 
during the evening or night shift -Current use of medications or OTC products that impact sleep -
Evidence of neurological abnormalities that could include the risks associated with lumbar puncture 
(e.g.papilledema, mass lesion, Chiari malformation).
Vulnerable Populations
Children Form
Pregnant women (if the study procedures may affect the condition of the pregnant woman or 
fetus) Form
Fetuses and/or Neonates Form
Prisoners Form
Other
x None of the above populations are included in the research study
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Populations vulnerable to undue inﬂuence or coercion
It is possible that a Penn employee could respond to a recruitment advertisement. They will be told that 
their participation or non-participation in the study will not in any way affect their employment with 
Penn.
Participant recruitment
Please describe the plan to equitably identify and recruit a diverse group of participants that is reﬂective 
of the population under study. If this is a multicenter protocol, the recruitment plan should describe the 
local (Penn) site's plan. Describe:how potential participants may be identiﬁed (review of medical 
records, Slicer Dicer, DAC reports including referrals from physician ofﬁces and clinics);who may 
approach potential participants;methods to achieve sample diversity and inclusiveness;what information 
may be presented to or discussed with them; andthe context and setting in which recruitment will 
happen.
Study advertising: Advertising will consist of newspaper advertisements, Penn Almanac, ﬂyers and 
brochures, iConnect, Craigslist, Reddit, data pull from PennChart and ResearchMatch. We only use 
University of Pennsylvania approved methods and materials that have current UPenn IRB approval. We 
plan to use our IRB approved shared pre-screen (IRB Protocol # 849262) as a method of recruitment.
Recruitment Materials
Is the research team using any recruitment materials? These may include but are not limited to: phone 
call scripts, radio/video scripts, ﬂyers/brochures, internet postings, email, letters to potential 
participants, letters to patient physicians, My Penn Medicine (MPM), other direct messaging, etc. For 
guidance regarding recruitment materials, please review the IRB's guidance on Participant Recruitment 
Materials online:https://irb.upenn.edu/recruitment
No
Use of Penn Media & Social Media Services
Will the recruitment plan propose to use any Penn media services (communications, marketing, etc.) for 
outreach via social media avenues (examples include: Facebook, Twitter, blogging, texting, etc.) or does 
the study team plan to directly use social media to recruit for the research?
No
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Page 19 of 25
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Subject compensation*
Will subjects be ﬁnancially compensated for their participation?
Yes
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If there is subject compensation, provide the schedule for compensation per study visit or session 
and total amount for entire participation, either as text or separate document
There will be compensation provided. Subjects will be compensated $25 for the screening visit, $50 for 
the home monitoring and $250 for the 22 hours spent in the lab. The total compensation for completing 
the study is $325. Payments will be made through the Clincard system.
Study Procedures
Suicidal Ideation and Behavior
Does this research qualify as a clinical investigation that will utilize a test article (ie- drug or biological) 
which may carry a potential for central nervous system (CNS) effect(s)? Centeral nervous system(CNS) 
effect: the ability of a test article to enter into and potentially interact with the central nervoous system 
(brain and spinal cord). Clinical Investigation: Any experiment that involves a test article and one or 
more human subjects that either is subject to requirements for prior submission to the Food and Drug 
Adminstration (FDA) under section 505(i) or 520(g) of the Federal Food, Drug, and Cosmetic Act, or is 
not subject to the requirements for prior submission to the FDA under these sections of the act, but, the 
results of which are intended to be submitted later to, or held for inspection by, the FDA as part of an 
application for a research or marketing permit. 
No
Procedures
At an initial visit, participants will provide informed consent; complete standard questionnaires on 
sleep, cognitive functioning, and demographics this visit, which will be completed remotely. All 
information will be collected via RedCAP. Participants will then complete an ambulatory sleep study at 
home to screen for the presence of sleep disordered breathing and to characterize their sleep 
architecture. There is the potential for the data from the ambulatory sleep study to reﬂect reactivity to 
the recording equipment (i.e. a ﬁrst night effect) this will be minimized by conducting the studies at 
home. Individuals who have evidence of sleep disorders based on the ﬁrst night recording will be 
excluded from further participation in the study. The criteria for deﬁning sleep disorders will be an 
apnea-hypopnea index greater than 15 events per hour for sleep apnea or a periodic limb movement 
index greater than 15 events per hour for PLMS. They will wear a wrist actigraph for one week and 
these data will be used to objectively assess sleep/wake patterns to determine eligibility based on 
habitual sleep duration.The actigraphy is a wrist-worn device that measures body movements. It is 
lightweight (17.5 g) and is worn like a wristwatch. Data are downloaded onto a personal computer and 
customized software uses the movement values to infer when the individual was awake or asleep. The 
methodology is commonly used to record sleep/wake patterns over several days. These data will be 
used to determine the individuals habitual sleep duration. In past studies, insomnia has most 
consistently associated with negative health outcomes when it is associated with objective evidence of 
short sleep duration (6 hours). As such, participants with insomnia who do not demonstrate average 
sleep duration 6 hours on actigraphy will not be eligible for further participation in the study. 
Participants who continue to be eligible following home sleep monitoring will then be studied in the 
Sleep Center on 11 Gates at the Hospital of the University of Pennsylvania for an overnight study. They 
will be arrive to the Sleep Center at 7:00 pm and will sleep overnight, following their habitual bedtime 
and wakeup time determined from the home actigraphy. Sleep will be monitored overnight using 
polysomnography. Standard polysomnographic procedures will be used to record the EEG, EOG, EMG, 
and EKG using an ambulatory system. Electrode placements of FpZ, CZ, OZ will be placed according 
to the International 10/20 system. Two EOG electrodes will be placed, positioned 1 cm below and 

Page 20 of 25
lateral to the outer canthus of the left eye and 1 cm above and lateral to the outer canthus of the right 
eye. Two surface EMG electrodes will be taped onto the chin 2 cm apart. Additional leads will be used 
to measure leg movements and breathing in order to rule out the presence of occult sleep disorders. Two 
electrodes will be taped over the anterior tibialis muscle of each leg to detect leg movements during the 
night. Flexible Resp-EZ belts will be placed around the abdomen and chest to measure breathing-
related movements during the night. A nasal cannula will be used to detect pressure and an oximeter 
probe will be placed on the ﬁnger to measure blood oxygen saturation. Records will be scored in 30-
second epochs according to standard criteria. PSG data will be used to compute standard sleep 
architecture variables of the amount of each stage of sleep in terms of minutes and percentage of total 
sleep time. In addition the following sleep continuity variables will be computed: sleep latency (SL; 
time from lights out to the ﬁrst epoch of stage 2 or higher), total sleep time (TST), wake after sleep 
onset (WASO; number of minutes spent awake between lights out and lights on), and sleep efﬁciency 
(SE; total sleep time divided by the total recording period). Additionally, our technicians will attached 
two sensors to the chest area of the subjects in order to measure respiration and test the sensors to see 
the accuracy of detecting sleep apnea. TatchSleep is a ﬂexible, thin, and wireless adhesive patch 
designed to collect physiological parameters related to sleep disorders in patients. Each patch consists 
of a wearable sensor and a bottom layer of double coat medical-grade adhesive. This adhesive is safe 
for patient use and enables the patch to stay afﬁxed to the body throughout the night. The sensor also 
connects directly to a battery which is hidden within the patch. During the study, patients will be asked 
to wear three patches. Data from the patches are transmitted wirelessly throughout the night to a 
companion mobile application, which stores the data for clinicians to upload to a sleep analysis 
platform. Upon waking, wires will be removed and the subjects will be allowed to shower. Those in the 
insomnia group who choose to participate in the optional second part of the protocol will have a fasted 
blood draw at this visit. Study staff will walk the subjects over to CHPS outpatient. Around 8:00 AM a 
lumbar puncture will be performed by a neurology fellow to collect 25 mL of CSF. Prior to the lumbar 
puncture the neurology fellow will conduct a neurological exam including fundoscopic exam, in order 
to rule out any contraindications to the procedure such as a coagulopathy or central mass lesion. If 
contraindications are found, the lumbar puncture will not be performed and the subject will be 
withdrawn from all further study procedures. If no contraindications are found, a small, specialized 
needle called a sprotte needle will introduced through an introducer. This type of needle has been 
demonstrated to reduce risk of headache. 25 mL of CSF will be collected and stored in polypropylene 
transfer tubes. In addition, bedrest for one or more hours immediately after the procedure will be 
recommended to the participant. Oral hydration will be encouraged to help reduce risk of headache. 
After ﬁnal samples are taken participants will have completed the protocol and will be free to leave. 
CSF Analysis:  Analysis 1: Endogenous ABO levels in human CSF will be measured in a blind fashion 
in a ﬂow-based ABO-speciﬁc sandwich ELISA using the Erenna immunoassay system (Millipore, 
Temecula, CA), described in Savage et al 2014 JN. In brief, Mercks proprietary 19.3 antibody coupled 
to paramagnetic microparticles will be used to capture ABO, repeatedly washed with assay-speciﬁc 
proprietary buffers, and detected using a ﬂuor-labeled detection antibody, 82E1 (IBL, Minneapolis, 
MN). Human CSF samples (100 uL/well) will be loaded in a blinded fashion in triplicate. The standards 
(ADDL), prepared in-house, will be run alongside CSF samples in triplicate using a 12-point ½ serial 
dilution between 42 pg/mL and 0.04 pg/mL. Statistical analysis of the data, including limit of detection 
(LOD) for the assay (deﬁned as 2 x SD Bkg/slope with percent coefﬁcient of variance 20%) and 
unknown ABO concentrations will be calculated using Singulex Sgx link and GraphPad Prism 
(GraphPad Software, Inc., San Diego, CA) software.  Analysis 2: OxA concentrations in CSF will be 
quantiﬁed 
by 
an 
in-house 
ELISA 
developed 
using 
Meso 
Scale 
Discovery 
(MSD) 
electrochemiluminescence detection technology platform (Gaithersburg, MD, USA). Puriﬁed 
polyclonal IgG (G-003-36, Phoenix Peptide, Burlingame, CA, USA), raised in rabbit against OxA 
(amino acids 16-33), will be used as a capture antibody. Goat anti-human polyclonal antibody against 
OxA (N-18) (sc-26491, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) will be used as a 
primary detection antibody. Sulfo-Tag labeled anti-goat antibody, raised in donkey, will be used as a 
secondary detection antibody and will be provided by MSD (R32AG-5). Blinded CSF samples will be 
run in triplicate alongside OxA standard (run as a 10-point 1/3 serial dilution between 30,000 and 4.57 
pg/mL). Statistical analysis of the data, including lowest detection limit (LDL) for the assay (deﬁned as 
2 x SD Bkg/slope with percent coefﬁcient of variance 20%) and unknown OxA concentrations will be 
calculated by extrapolating a nonlinear regression curve (sigmoidal, 4PL, X is log (Concentration)) and 
will be corrected for weight by 1/Y^2 using GraphPad Prism (GraphPad Software, Inc., San Diego, CA) 
software.
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Page 21 of 25
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Deception
Does your project use deception? Deception could be considered any direct misinformation presented to 
the subject or omission of key information pertaining to the design or nature of the project. 
No
International Research
Are you conducting research outside of the United States? 
No
Analysis Plan
Paired-samples t-tests will be conducted to compare each of the CSF analytes between patients with 
chronic insomnia and matched good sleepers. Multiple regression analyses will be used to examine 
whether CSF orexin levels mediate the relationship between chronic insomnia and AB markers. 
Mediation analyses will be conducted using a series of linear regression models in which group 
(insomnia or control) and orexin levels will be treated as independent variables and AB markers will be 
treated as the dependent variables.
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Data conﬁdentiality
x Paper-based records will be kept in a secure location and only be accessible to personnel involved 
in the study.
x Computer-based ﬁles will only be made available to personnel involved in the study through the 
use of access privileges and passwords.
x Prior to access to any study-related information, personnel will be required to sign statements 
agreeing to protect the security and conﬁdentiality of identiﬁable information.
x Wherever feasible, identiﬁers will be removed from study-related information.
A Certiﬁcate of Conﬁdentiality will be obtained, because the research could place the subject at 
risk of criminal or civil liability or cause damage to the subject's ﬁnancial standing, 
employability, or liability.
A waiver of documentation of consent is being requested, because the only link between the 
subject and the study would be the consent document and the primary risk is a breach of 
conﬁdentiality. (This is not an option for FDA-regulated research.)
Precautions are in place to ensure the data is secure by using passwords and encryption, because 
the research involves web-based surveys.
Audio and/or video recordings will be transcribed and then destroyed to eliminate audible 
identiﬁcation of subjects.
Subject Conﬁdentiality
Each participant will be assigned a study ID #. All study-related paperwork and computer ﬁles will only 
utilize the ID #. All study ﬁles will be stored behind a double lock system at 3535 Market Street, Suite 
670, Room 698. Only study staff will be able to access the data. All study records will be maintained in 
locked ﬁle cabinets for paper records and electronic ﬁles will be stored on an institutionally secured & 
managed network drive. The master ﬁle linking subjects with their ID #s will be kept in a separate 
locked ﬁle cabinet. Following completion of the study and all manuscripts are written, paper records 
will be archived and stored in accordance with regulations for retention of research records. PHI will be 
removed from electronic ﬁles at that point as well.
Sensitive Research Information*
Does this research involve collection of sensitive information about the subjects that should be excluded 
from the electronic medical record? [NOTE: This does not apply to: 1) research information that would 
not normally be included in the electronic medical record or 2) information that is in the electronic 
medical record as part of clinical care.]

Page 22 of 25
No
Subject Privacy
Privacy refers to the person's desire to control access of others to themselves.  Privacy concerns people, 
whereas conﬁdentiality concerns data. Describe the strategies to protect privacy giving consideration to 
the following: The degree to which privacy can be expected in the proposed research and the safeguards 
that will be put into place to respect those boundaries. The methods used to identify and contact 
potential participants. The settings in which an individual will be interacting with an investigator. The 
privacy guidelines developed by relevant professions, professional associations and scholarly 
disciplines (e.g., psychiatry, genetic counseling, oral history, anthropology, psychology). 
Participants records will only utilize a study ID # in order to avoid violation of privacy. Names of 
participants will not be shared outside of the study staff, except to the extent required by law. 
Participants will be asked to indicate their preferred means of contact (phone, email, etc). All study 
visits will take place in a private room and the door will be closed to maintain privacy.
Disclosures
Will any data or specimens from Penn participants OR other research generated work product (e.g., 
intellectual property) be disclosed to any individuals, entities, or vendors, etc. outside of Penn?
No
Data Protection*
x Name
x Street address, city, county, precinct, zip code, and equivalent geocodes
x All elements of dates (except year) for dates directly related to an individual and all ages over 89
x Telephone and fax number
x Electronic mail addresses
x Social security numbers
x Medical record numbers
Health plan ID numbers
Account numbers
Certiﬁcate/license numbers
Vehicle identiﬁers and serial numbers, including license plate numbers
Device identiﬁers/serial numbers
Web addresses (URLs)
Internet IP addresses
Biometric identiﬁers, incl. ﬁnger and voice prints
Full face photographic images and any comparable images
Any other unique identifying number, characteristic, or code
None
Does your research request both a waiver of HIPAA authorization for collection of patient information 
and involve providing Protected Health Information ("PHI") that is classiﬁed as a "limited data set" 
(city/town/state/zip code, dates except year, ages less than 90 or aggregate report for over 90) to a 
recipient outside of the University of Pennsylvania covered entity?
No
Tissue Specimens Obtained as Part of Research*
Are Tissue Specimens being obtained for research?
Yes

Page 23 of 25
Tissue Specimens - Collected during regular care*
Will tissue specimens be collected during regulator clinical care (for treatment or diagnosis)?
No
Tissue Specimens - otherwise discarded*
Would specimens otherwise be discarded?
No
Tissue Specimens - publicly available*
Will tissue specimens be publicly available?
No
Tissue Specimens - Collected as part of research protocol*
Will tissue specimens be collected as part of the research protocol?
Yes
Tissue Specimens - Banking of blood, tissue etc. for future use*
Does research involve banking of blood, tissue, etc. for future use?
Yes
Genetic testing
If genetic testing is involved, describe the nature of the tests, including if the testing is predicative or 
exploratory in nature. If predictive, please describe plan for disclosing results to subjects and provision 
of genetic counseling. Describe how subject conﬁdentiality will be protected Note: If no genetic testing 
is to be obtained, write: "Not applicable."
Not Applicable
Consent
1. Consent Process
Overview
Study personnel will meet with each individual virtually and describe the study in detail. Individuals 
will be provided with the combined consent / HIPAA form to read. They will have the opportunity to 
ask questions and discuss participation with other family members. Individuals will be asked to sign a 
consent form on RedCAP. Individuals who continue participation will provide written informed consent 
will be given a copy of the consent form for their records at their overnight sleep study.
Children and Adolescents
Not Applicable.
Adult Subjects Not Competent to Give Consent
Not Applicable.
2. Waiver of Consent
Waiver or Alteration of Informed Consent*
No Waiver Requested
Minimal Risk*
Impact on Subject Rights and Welfare*
Waiver Essential to Research*
Additional Information to Subjects
Written Statement of Research*
No

Page 24 of 25
If no written statement will be provided, please provide justiﬁciation
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Risk / Beneﬁt
Potential Study Risks
There is no substantial risk associated with the completion of the initial evaluation, though the subject 
will be asked to respond honestly to personal questions. Risks associated with polysomnography: There 
are few risks associated with the sleep study procedure. However, some people do experience minor 
discomfort (dry skin, rash) from having the skin cleansed and sensors placed on the skin over the course 
of the in laboratory studies. Risk of Lumbar Puncture: There is the risk of brain swelling or herniation if 
the subject has particular neurological abnormalities (e.g. papilledema, mass lesion, Chiari 
malformation). The neurology fellow performing the LP will conduct a neurological exam with 
fundoscopic exam to rule out these contraindications and will only proceed if there is no evidence of 
these risks. The lumbar puncture may cause pain at the site where the needle goes in and the spinal ﬂuid 
is taken. There is a small risk of infection or bleeding. After the lumbar puncture, there is a risk of 
headache. To minimize the risk of a headache, the doctor will use a small, specialized needle, a sprotte 
needle introduced through an introducer. This type of needle has been demonstrated to reduce risk of 
headache. In addition, bedrest for one or more hours immediately after the procedure will be 
recommended to the participant. Finally, oral hydration will be encouraged to help reduce risk of 
headache. If headache does occur, it is usually mild and can be controlled with bedrest, hydration (with 
oral ﬂuids), and acetaminophen or NSAIDS. Rarely, the headache is severe and may require additional 
treatment with a blood patch. In this procedure, a small amount of the patient's own blood is injected 
into the lumbar puncture site. This procedure is generally effective in stopping the headache. Although 
very rare, it is possible to have an allergic reaction to the local anesthetic used for the lumbar puncture. 
Signs of an allergic reaction include swelling and/or a rash on the skin where the anesthetic was 
injected. The patient will be asked about prior allergies to lidocaine and will be monitored for evidence 
of this reaction. There is a small risk of hemorrhage related to lumbar puncture. This risk will be 
minimized by checking a platelet count and coagulation studies (PT/PTT) prior to the lumbar puncture. 
To further minimize any possible risk, the lumbar puncture will be done by a neurology resident who is 
speciﬁcally trained in the procedure. Potential sources of research risk of this proposed investigation 
include the burden to participants cause by the amount of time asked of them, performance of the 
actigraphy and sleep study, and the conﬁdentiality of data obtained. We do not consider the time 
demands on participants a serious risk and they can withdraw at any time. In addition, study staff will 
be trained to minimizr the burden on research involving human participants, breach of conﬁdentiality of 
personal data obtained as part of this study is a potential risk to participants.
Potential Study Beneﬁts
It is possible that the sleep study could identify sleep disorders that participants are unaware of, 
enabling them to seek treatment. There are no other beneﬁts to the individual for participation. The 
knowledge we expect to gain from this study will be used to better understand the relationship between 
chronic insomnia and dementia.
Alternatives to Participation (optional)
The subject can choose to not participate.
Data and Safety Monitoring
Principal Investigator
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Risk / Beneﬁt Assessment
The procedures in this study are greater than ordinarily encountered in daily life, but they are 
commonly used without problems in the context of biomedical research. As such this study is moderate 

Page 25 of 25
risk.
General Attachments
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