Lutein & Zeaxanthin in Pregnancy - Carotenoid Supplementation During Pregnancy: Ocular and Systemic Effects
Phase: PHASE2
Conditions: Nutrient Deficiency, Pregnancy Related
Sponsor: Paul S. Bernstein

Study Protocol and Statistical Analysis Plan for NCT03750968 
Lutein & Zeaxanthin in Pregnancy – Carotenoid Supplementation during Pregnancy: Ocular and Systemic 
Effects 
The following pages contain the IRB approved study protocol and statistical analysis plan at the most 
recent renewal approved on 21 December 2022. 
 

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IRB_00116610
1. Contacts and Title
Date: Tuesday, May 2, 2023 2:01:03 PM
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
1. Study Introduction
1. Responsible Investigator:
Paul Bernstein
Email
Training
CoI Date
paul.bernstein@hsc.utah.edu 7/27/2021 MCG
4/3/2023
a. Position of the Investigator:
Faculty or Non-Academic Equivalent
Student
Staff
Resident/Fellow
Other
2. Contact Persons for the Responsible Investigator:
Name
Email
Training
Susan Allman
susan.allman@hsc.utah.edu
1/30/2023 MCG
Melanie Fiuza
melanie.fiuza@hsc.utah.edu
CG
Deborah Harrison
deborah.harrison@hsc.utah.edu
1/31/2023 MCG
Elizabeth Nuttall
Elizabeth.Nuttall@hsc.utah.edu
1/4/2023 MCG
Katie Rogers
katie.rogers@utah.edu
6/17/2022 MCG
3. Guests of the Responsible Investigator:
Last Name
First Name
E-Mail
There are no items to display
4. What type of application is being submitted?
New Study Application (or Amendment/Continuing Review)
5. Title Of Study:
Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid Supplementation During Pregnancy: Ocular and Systemic
Effects
6. Study Purposes and Objectives:
The primary objective of this study is to characterize the carotenoid status of mothers during pregnancy, specifically to determine if
prenatal supplementation counteracts maternal systemic and ocular carotenoid depletion. 

The primary outcome measure will be change in carotenoid levels from enrollment to final study visit (birth of child) as measured in
serum, skin and the macula by high-performance liquid chromatography (HPLC), resonance Raman spectroscopy, and macular pigment
imaging, respectively.
7. Is this a multi-site study, where more than one site needs IRB approval?
    Yes  No
8. Background and Introduction:
The human macula has a high concentration of the dietary carotenoids lutein and zeaxanthin which results in a yellow spot centered on
the fovea, the macula lutea.  Carotenoids are abundant in plants, fruits, and vegetables, and they are thought to play important roles in
the physiologic function of the retina and other tissues (Scott et al., 1996; Scarmo et al., 2010; Zimmer et al., 2007; Bernstein et al.,
2016).  Of the hundreds of carotenoids found in nature, 10 to 15 are detectable in human serum, but only lutein, zeaxanthin, and their
metabolites are present in the retina (Bone et al., 1985; Khachik et al., 1997).  The potential antioxidant and photoprotective effects of
carotenoids, especially with regard to age-related macular degeneration (AMD), have been studied extensively in the laboratory and in
clinical studies (Seddon et al., 1994; Bernstein et al., 2002; Eye Disease Case-Control Study Group, 1993), and recent reports have
demonstrated a role of dietary and supplemental carotenoids in slowing or preventing AMD (Age-Related Eye Disease Study (AREDS)
Report No. 22, 2007; AREDS2 Report No. 3, 2014). 
Studies also suggest a functional role for the macular carotenoid pigment earlier in life, at a time when they may enhance contrast
sensitivity, decrease glare disability, and even increase visual acuity (Kvansakul et al., 2006; Stringham et al., 2008; Olmedilla et al.,
2003).  The physiological accumulation of the macular carotenoid pigments occurs even in utero (Malone, 1975; Dimenstein et al.,
1996).  Investigators have recently shown that the macular pigment is detectable immediately after birth, correlates with infant and
maternal serum zeaxanthin levels, and progressively increases through the first seven years of life (Bernstein et al, 2013).  This
suggests that the macular carotenoids play physiological and protective roles throughout the lifecycle and may be particularly important
during infant visual development. 
Prenatal vitamin and micronutrient supplementation is standard-of-care for pregnant women worldwide; however, with the exception of
a few ingredients, most prenatal supplementation guidelines are not yet supported by substantial prospective clinical research.  Recently,
prenatal supplements with added lutein and zeaxanthin have entered the American market with the stated intentions of enhancing infant
visual and neural development and maintaining maternal health.  Although clinical trials were never performed to support these
contentions, it is physiologically plausible from the neonate’s perspective because these dietary carotenoids are selectively concentrated
in human ocular and neural tissue in utero, especially during the third trimester of pregnancy.
From the mother’s perspective, the last trimester of pregnancy is a time when she must transfer some of her carotenoid stores to the
developing infant via the placenta, potentially putting her at risk for depletion systemically and in her ocular tissues.  On review of the
published literature, there are conflicting data regarding systemic maternal carotenoid status throughout pregnancy, and absolutely
nothing is known about maternal macular pigment levels in the eye during pregnancy.  Some, but not all, studies report lower serum
carotenoid levels in pregnant women. Bernstein and others (Henriksen et al., 2013; Kiely et al., 1999; Zhang et al., 2001) have reported
that mothers who did not take lutein or zeaxanthin supplements during pregnancy had >50% reductions of serum lutein and zeaxanthin
concentrations and ~20% lower total skin carotenoids at the time of delivery when compared to our clinic’s average of unsupplemented
non-pregnant adults. 
Prospective, controlled clinical trials to demonstrate the benefits of carotenoid supplementation during pregnancy have never been
conducted.  To obtain data relative to the feasibility of such trials, this study will be a comprehensive, prospective assessment of
prenatal lutein + zeaxanthin supplementation on maternal and infant ocular and systemic biomarkers of carotenoid status throughout
pregnancy. 
Please see pp. 27- 30 of the protocol for the list of literature cited.

IRB_00116610
2. Study Location and Sponsors
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy:
Ocular and Systemic Effects
 
2. Study Location and Sponsors
1. Add all locations applying for approval of research via the University of Utah IRB or Human Research
Protection Program (HRPP).
Click the appropriate button(s) below to add locations:
 
Site Name
Investigators Name
Covered Entity
Sub Sites
View University of Utah
Paul Bernstein
Yes
 
2. Will a Central IRB (CIRB) or Single IRB (SIRB) model be used for review of this study for the sites listed in
this application?
  Yes  No
3. Indicate the source(s) of funding obtained or applied for to support this study.
 
Sponsor
Sponsor Type Sponsor Contact Information
Prime
Sponsor
Prime
Sponsor
Type
OrgID
View DHHS NATIONAL
INSTITUTES OF HEALTH
Federal
Government
 
 
 
10154
View HEIDELBERG
ENGINEERING GMBH
Industry
Heidelberg Engineering GmbH
Max-Jarecki-Straβe 8
69115 Heidelberg
Germany
www.HeidelbergEngineering.com
 
 
00017492
4. Does this study have functions assigned to a Contract Research Organization (CRO)?
  Yes  No
5. Does this study involve use of the Utah Resource for Genetic and Epidemiologic Research (RGE)?
Examples: Utah Population Database (UPDB), Utah Cancer Registry (UCR), All Payers Claims Database (APCD),
etc.
  Yes  No

IRB_00116610
View/Edit
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
Addition of a Site
1. Site Name:
University of Utah
2. Site Principal Investigator
Mark if Same as Responsible Investigator (syncs with investigator on
the first page) 
Paul Bernstein
Email
Training
CoI Date
paul.bernstein@hsc.utah.edu 7/27/2021
MCG
4/3/2023
a. Position of the Site Principal Investigator
Faculty or Non-Academic Equivalent
b. Will the Site PI consent participants?    Yes  No
3. Site Contact Persons, if different from the Site PI:
Mark if Same as Contacts for Responsible Investigator (syncs with
contacts on the first page)
Name
Email
Training
Susan Allman
susan.allman@hsc.utah.edu
1/30/2023 MCG
Melanie Fiuza
melanie.fiuza@hsc.utah.edu
CG
Deborah Harrison
deborah.harrison@hsc.utah.edu
1/31/2023 MCG
Elizabeth Nuttall
Elizabeth.Nuttall@hsc.utah.edu
1/4/2023 MCG
Katie Rogers
katie.rogers@utah.edu
6/17/2022 MCG
4. Site Staff and Sub-Investigators
Name
Email
Training
Obtaining
Consent CoI Date
Emmanuel
Kofi Addo
u1272149@utah.edu
9/13/2022
MG

5/2/2023
Mudsar
ahmad
u0686085@utah.edu
12/1/2021
MCG

4/26/2023
Susan
Allman
susan.allman@hsc.utah.edu
1/30/2023
MCG

1/14/2023
Claire
Ausbeck
U1068666@umail.utah.edu
6/21/2021
MCG

3/20/2023
Rebecca
Cobes
u6035959@utah.edu
4/19/2021
SMCG

3/6/2023
Melanie
Fiuza
melanie.fiuza@hsc.utah.edu
CG

2/2/2022

Name
Email
Training
Obtaining
Consent CoI Date
Carson
Foust
u6034898
10/13/2021
MCG

6/28/2022
Deborah
Harrison
deborah.harrison@hsc.utah.edu 1/31/2023
MCG

5/2/2023
Mary
Elizabeth
Hartnett
me.hartnett@hsc.utah.edu
11/16/2022
MCG

10/4/2022
Robert
Hoffman
Robert.hoffman@hsc.utah.edu
10/27/2021
MG

10/11/2022
Ashley
Joseph
Ashley.joseph@hsc.utah.edu
3/9/2021
MCG

3/9/2023
Alexandra
Nestel
u1183906@utah.edu
10/6/2021
SMCG

1/9/2023
Elizabeth
Nuttall
Elizabeth.Nuttall@hsc.utah.edu 1/4/2023
MCG

5/2/2023
Kelliann
Ordonez
kellian.farnsworth@hsc.utah.edu 6/6/2022
MCG

5/2/2023
Parker
Pearson
u0860888.umail.utah.edu
7/20/2021
MCG

3/10/2023
Rose
Peckham
rose.peckham@hsc.utah.edu
9/22/2020
MCG

4/18/2023
Emily
Powers
emily.powers@hsc.utah.edu
2/25/2022
MCG

5/2/2023
Danae
Reyes
danae.reyes@hsc.utah.edu
4/19/2023
MCG

4/17/2023
Lydia Sauer lydia.sauer@hsc.utah.edu
5/18/2020
MG

4/28/2023
Mohsen
Sharifzadehsharifzadeh.mohsen@gmail.com 

11/17/2022
Michael
Varner
michael.varner@hsc.utah.edu
4/24/2023
SMCG

4/24/2023
Kelly
Vorwaller
kelly.vorwaller@hsc.utah.edu
3/7/2023
MCG

11/14/2022
Joseph
Worden
joseph.worden@hsc.utah.edu
5/13/2021
MCG

12/5/2022
5. Site Guests:
Name
Email
Training
Kathryn Szczotka
kathryn.szczotka@hsc.utah.edu
4/28/2021 MCG
6. Select HIPAA coverage for this study:
Study procedures will be conducted within a HIPAA Covered Entity at this site
(HIPAA Privacy Rule applies)
7. Select the study procedures that will be conducted at this site:
Recruitment
Consent/Enrollment

Research observation/intervention with participants
Data collection
Data analysis
Do you have an enrollment goal or anticipated enrollment number for
this site?
 
Yes
No
Enrollment Number:
60 mothers and 60 infants  
8. Select the University of Utah department responsible for this research:
OPHTHALMOLOGY-CLINICAL STUDIES
9. Add any additional sites that are part of this performance group
There are no items to display

IRB_00116610
IRB Smart Form
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
Sponsor Information
a. Are you receiving award or contract management for the
sponsored funds through the University of Utah Office of
Sponsored Projects?
  Yes  No
If yes, select the associated OSP Proposal ID/DSS through eAward to link it to the
ERICA system.
You must have a fully approved Proposal ID/DSS number through eProposal which will show up
in eAward after OSP has integrated the ID. To access the eAward application, use the
instructions on the OSP website.
Link to a Proposal ID/DSS through eAward
Proposal ID/DSS: 10046346
PI: BERNSTEIN,PAUL S
Sponsor: DHHS NATIONAL INSTITUTES OF HEALTH
Prime Sponsor:
Department:
Short Title: CAROTENOID SUPP DUR PREGNANCY
Sponsor Award Number:
Type: Federal Government
Award Start Date: 4/1/2018
Award End Date: 3/31/2020
Prime Sponsor Type:

IRB_00116610
IRB Smart Form
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
Sponsor Information
a. Are you receiving award or contract management for the
sponsored funds through the University of Utah Office of
Sponsored Projects?
  Yes  No
If no, indicate how the funds are being received:
Other
If 'Other', please explain how funds are being
received:
Heidelberg has provided Dr. Bernstein with a beta version of the macular pigment imaging
software at no cost. It must be used under IRB approval as it is not yet FDA approved.
Heidielberg will not be receiving data from this study and has no interest in the conduct of the
study.
Sponsor:
HEIDELBERG ENGINEERING GMBH
Previously, the following data was entered on your IRB
application:
Sponsor Contact Information:
Heidelberg Engineering GmbH
Max-Jarecki-Straβe 8
69115 Heidelberg
Germany
www.HeidelbergEngineering.com

IRB_00116610
3. Participants
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
3. Participants
1. Ages of Participants:
Less than 7 years old
(Parental permission form needed)
18 and older
(Consent form needed)
2. Specific age range of participants (e.g., 7-12 years old, 60+, etc.):
Pregnant women 18 or older and their infants
3. Indicate any vulnerable participant groups (other than children) included:
Pregnant women and fetuses (CFR Part 46, Subpart B)
 
  If "Other", please specify: 
 
  If "None" and no children are involved, answer the following question.
Has the participant selection process overprotected potential subjects who are considered
vulnerable so that they are denied opportunities to participate in research?
  Yes  No
4. Number of participants to be included and/or enrolled in this entire study, across all study locations: 60 mothers
and 60 infants
 
At Utah prior to October 2019: 60 mothers and 60 infants
5. Characteristics of Participants/Inclusion Criteria:
Pregnant women, 18 or older of all races and ethnicities who:
have an uncomplicated obstetric history
plan to deliver either vaginally or by Caesarian section at the University of Utah for their current pregnancy
 
6. Participant Exclusion Criteria:
Women will be excluded if they:
Have regularly taken carotenoid supplements containing more than 0.5 mg of lutein and/or zeaxanthin daily during the past six
months.
Have significant eye disease associated with macular pigment abnormalities such as Stargardt disease, albinism, or macular
telangiectasia type II (MacTel).
Have any conditions associated with high-risk pregnancies such as adolescent pregnancy, multiparity, current or past history of
diabetes, pre-eclampsia, previous premature delivery, drug abuse, or other significant medical illness. 

7. Is a substantial percentage of the participant population anticipated to be non-English
speaking?
  Yes  No

IRB_00116610
- Vulnerable Populations
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
 
Vulnerable Populations
 
Justification Requirements for the Inclusion of Vulnerable Populations
1. How does the nature of the research require or justify using the proposed subject population?
The main objectives of the study are to describe mothers' carotenoid status during pregnancy, and the relation between
maternal nutritional status and its effect on the newborn.
2. Would it be possible to conduct the study with other, less vulnerable subjects?
  Yes  No
 
  If yes, justify the inclusion of vulnerable subjects:
3. Is this population being included primarily for the convenience of the researcher?
  Yes  No
 
  If yes, explain:

IRB_00116610
4. Study Information
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
 
4. Study Information
1. Design of Study (select all that apply):
Non-Experimental and/or Descriptive Research Design:
There are no items to display
Experimental and/or Interventional Research Design:
Blinded Trial (Single or Double Blinded)
Randomized Trial
Phase II Clinical Trial
Development of a research resource (repositories, databases, etc.)
There are no items to display
 Other
2. Does your study involve the use of any placebo?
  Yes  No
3. Length of entire study, from initiation through closeout:
2 years
4. How will participants be recruited or identified for inclusion in the study?
a. Select all methods that will be used:
In-person contact (e.g., patients, students, etc.)
Written or electronic record review
Written advertising (flyers, brochures, website postings, newspaper ads, etc.)
b. Describe the recruitment/participant identification process in detail (e.g. who will review charts or
records, who can refer participants to the study, where will flyers be posted, how often will recruitment
letters be sent, when will follow-up phone calls be made, etc.):
Mothers who are eligible for the study will be recruited from the OB/GYN Clinics of the University of Utah during a first trimester
prenatal visit (prior to week 13), with agreement from their attending Obstetrician.
Recruitment brochures will be posted in clinic areas.
A web-based tool, the Human Subjects Recruitment Tool (HSRT), will be used to screen for potential patients who meet the IRB
approved eligibility requirements and have a clinic appointment/inpatient visit at one of the approved clinic and/or inpatient
locations. 
We will also screen patient appointment logs through a Waiver of Authorization to identify potential patients who meet initial
eligibility criteria. 
Potential participants will then be approached about the study during one of their prenatal clinic visits.  Study personnel will
describe the study in detail and review the study protocol with the patient.  

Data from the Human Subjects Recruitment Tool (HSRT) will become unavailable the day the IRB expires or when the research
team notifies the EDW that the recruitment period closes.
5. How will consent be obtained?
Informed Consent Process (with or without a document)
6. Describe all the procedures chronologically, from screening/enrollment through study closeout, which will be
completed in the research project.
Study Visit Schedule
Initial evaluation of each mother’s carotenoid status will be obtained prior to starting any study supplements.  Subsequent evaluations
while participants are taking the study supplements will be performed in conjunction with routine prenatal visits to their Obstetrician, at
approximately 22-26 weeks gestational age and again at 37-39 weeks gestational age.  All mothers will undergo a final assessment
within two weeks of giving birth.
Infants’ evaluations will be performed in the first two weeks of life, either during the original hospital stay or at a follow up outpatient
clinic visit.  
 
Screening/
Baseline
Maternal Supplementation
Visit:
 
Timeframe:
T1
T2
T3
Birth
Before 14 Wks
GA
22-26 Wks
GA
37-39 Wks
GA
0 to
2 Wks
Informed Consent
X
 
 
 
Randomization
X
 
 
 
Maternal visual acuity and contrast sensitivity
X
X
X
X
Maternal nutritional surveys
X
X
X
X
Dilated eye examination
X
 
 
 
Maternal serum carotenoids
X
X
X
X
Maternal macular pigment imaging
X
X
X
X
Maternal skin carotenoids
X
X
X
X
Dispense prenatal supplement and do pill counts
X
X
X
X
Infant cord blood carotenoids
 
 
 
X
Infant macular pigment imaging
 
 
 
X
Infant foveal imaging (sdOCT)
 
 
 
X
Infant skin carotenoids
 
 
 
X
 
Unscheduled Visits
Mothers may be seen for Unscheduled Visits if deemed necessary for repeat measurements or follow-up of Adverse Events.  If a mother
delivers her baby prematurely, she and her infant will remain in the study and will be asked to complete the final study visit.
Description of Study Assessments:
Visual Function - Manifest refraction, and measurement of best-corrected visual acuity and contrast sensitivity of the mothers will be
obtained by certified ophthalmic technicians using standardized protocols.  The study staff performing visual acuity will be masked to the
treatment assignment. Best-corrected visual acuity testing will be assessed on ETDRS back-lit charts starting at a distance of 4 m, and
should precede any examination requiring administration of eye drops to dilate the eye or any examination requiring contact with the
eye.  Contrast sensitivity will be measured by the Pelli-Robson threshold contrast sensitivity chart at 1 m. 

Maternal Eye Exam - The complete ophthalmic exam will consist of the following:
External examination of the eye and adnexa.
Routine screening for eyelids/pupil responsiveness (including ptosis, abnormal pupil shape, unequal pupils, abnormal reaction to
light and afferent pupillary defect).
Slit-lamp examination [cornea, anterior chamber, iris, lens, aqueous reaction (cells and flare).
Dilated fundus exam of the study eye including evaluation of retina and vitreous (i.e. posterior segment abnormalities, retinal
hemorrhage/detachment, and vitreal hemorrhage density and vitreous cells).
IOP measurement - A measurement of intraocular pressure will be conducted using a Tono-pen tonometer. This should be
performed prior to dilating the eyes and the same method should be used for all measurements in the same subject throughout
the study.
Skin Carotenoid Levels - A high-sensitivity scanner (Raman device) suitable for measurements of infants and adults will be used for
this study.  The measurements are taken by placing a probe on the subject’s palm of the hand (adults) or sole of the foot (infants) with a
special light source that does not generate heat and is harmless to one’s vision as long as it is not viewed directly for a long time (similar
in risk to a laser pointer).  The measurements require 30 seconds of skin contact and another 30 seconds to obtain the reading.  The
measurement is repeated 3 times to confirm the accuracy, so a total of 3 minutes of assessment is needed.  
Infant Macular Pigment Measurements - Infant macular measurements will be performed using blue light reflectometry.  The
infant’s pupils will be dilated with Cyclomydril drops (standard-of-care for dilated eye examinations of newborns), and then the swaddled
baby’s eyes will be opened with a pediatric lid speculum.  Posterior pole 80-degree images centered on the fovea will be taken with a
retinal camera by a certified ophthalmic photographer under the supervision of a Pediatric Ophthalmologist using its optional blue light
source and deliberately omitting the fluorescein angiography barrier filter in the collection light path.  Color images will also be taken to
facilitate identification of key retinal landmarks.  Total image acquisition time is just a few minutes.
Infant Foveal Anatomy - The sdOCT (Bioptigen) is an FDA-approved handheld portable unit that is used to image the foveal anatomy
of premature and full-term infants. Swaddled infants will have their eyelids gently opened by the certified ophthalmic photographer or a
Pediatric Ophthalmologist.  Vertical and horizontal scans will then be acquired.  The OCT images will be obtained prior to the contact
images with the retinal camera.
Maternal Macular Pigment Levels - Mothers’ macular pigment will be measured using the dual wavelength autofluorescence method
which measures attenuation of lipofuscin autofluorescence by blue absorbing macular pigment.  The subject looks at a fixation target
with her dilated study eye for about 30 seconds as her macula is scanned sequentially with alternating 486 nm (blue) and 518 nm
(green) lasers, and autofluorescence images are collected.  Macular pigment images are prepared by digitally subtracting the green
image from the blue image using appropriate correction factors to compensate for the absorption spectrum of the macular carotenoid
pigment and then analyzed using macular pigment analysis software after setting the zero point at 9 degrees of eccentricity.  This
instrument and software has proven to be highly reliable and reproducible, especially when measuring macular pigment volume under
the curve at 9 degrees.
Serum Carotenoid Levels - Blood samples obtained from mothers and from infant cord blood will be analyzed for serum carotenoid
content using well-established laboratory protocols that can provide baseline separations of all common dietary carotenoids.  Whenever
possible blood samples will be obtained by piggy backing onto a routine clinical blood collection.
Dietary Questionnaires - At each study visit mothers will be asked to complete the LZQ quantitative food frequency questionnaire 
that captures ~90% of the lutein/zeaxanthin foods consumed in the US,  based on National Health and Nutrition Examination Survey
data.
Safety Evaluations - Any clinically significant abnormalities persisting at the end of the study/ early withdrawal will be followed by the
investigator until resolution or until a clinically stable endpoint is reached. The study includes procedures to monitor safety, including
complete Ophthalmic exams and monitoring of adverse events.  
Optional Specimen Collection and Banking Sub-Study
Participants will be asked to allow a sample of placenta tissue to be collected and stored for future research related to maternal to infant
carotenoid transport on a tissue level.
Participants will be asked to provide a saliva sample to be stored and used for future research related to the genetics of carotenoid
metabolism enzymes.
Participants will be asked to allow a portion of their blood collected at study visits to be stored for future research related to the genetics
of carotenoid metabolism.
Participation in these procedures is optional and participants may decline any or all of them and still participate in the main study. 
Participant identifiers will be stored separately from the banked samples and participants will be able to withdraw their samples if they so
desire.
Banked samples may be shared with other researchers, who must have IRB approval for their use and material/data transfer
agreements with the University of Utah as applicable.

7. Are all procedures for research purposes only (non-standard or non-standard of care procedures)?
  Yes  No
If no, list the procedures that are performed for research purposes only (non-standard or non-standard
of care procedures):
All Protocol-specified procedures are for research purposes only, with the exception of dispensing prenatal supplements. 
Expectant mothers will be taking prenatal supplements whether or not they agree to participate in this study.  
8. Is there a safety monitoring plan for this study?
  Yes  No
9. Provide a summary of the statistical methods, data analysis, or data interpretation planned for this study.
Factors for determining the proposed sample size (e.g., power) should be stated.
Statistical Analysis
The study outcome data will be analyzed by a consultant from the University of Utah Study Design and Biostatistics Center of the Center
for Clinical and Translational Science.
Image analysis of retinal camera macular pigment measures will be conducted in Dr. Bernstein's laboratory. Foveal anatomy parameters
such as width, depth, and layer structure will be assessed by Drs. Hartnett and Bernstein using methods based on previously published
protocols. 
Sample Size Calculation and Power Considerations
Statistical power and sample size (N) for one of the primary outcome measures, maternal skin carotenoids at birth, was determined
using data from the previous study by Henriksen et al. (2013) in which the average maternal skin carotenoids ± SD at birth was 34000
± 8300. This value is 20% lower than the University of Utah Moran Eye Center clinic average value of ~42,500 Raman counts reported
for the ancillary AREDS2 study (Bernstein et al., 2012).  With power of 0.90 and alpha 0.05, a sample size of 20 was calculated for each
group in order to detect and prevent a 20% decline during pregnancy.  In order to accommodate subsequent ineligibility due to
premature birth, low birth weight, or other problems (~10%) and to plan for expected noncompliance and loss to follow up (~20%), we
intend to enroll 30 subjects in the Carotenoid Supplementation Group and another 30 in the Control Group. 
The other outcome measures (maternal ocular carotenoid depletion during pregnancy, infant carotenoid status at birth, and the
exploratory outcome measures of foveal maturity at birth and visual function changes during pregnancy) are not as well characterized,
but we estimate that a similar sample size of 20 patients per group will be sufficient to detect differences in these indices.
Statistical Analysis Sets
The Intent-to-Treat set will include all randomized subjects who complete the Baseline Visit carotenoid status evaluations and receive
study supplements.  Subjects will be analyzed by the supplement arm assigned at the Baseline Visit.
A modified Intent-to-Treat set will include all randomized subjects who receive investigational product and complete carotenoid
evaluations for at least one trimester study visit while utilizing study supplements.
Efficacy Analyses
The primary, secondary and exploratory efficacy analyses will be performed using the modified Intent-to-Treat subject set.  Paired t-tests
will compare the carotenoid status at enrollment and at the final study visit of the mothers receiving carotenoid supplementation to
mothers not receiving carotenoid supplementation.  We will also compare carotenoid status of infants whose mothers received
carotenoid supplementation to infants of mothers without carotenoid supplementation. Significance will be set at 2-tailed P<0.05.  The
associations between maternal and infant carotenoid status will be assessed with regression analysis.  
Subgroup analyses will be performed to assess the influences of maternal dietary carotenoid intake, compliance with study supplement
use, co-existing medical conditions, BMI, infant gender, and other factors on our study results, with proper attention to the effects of
multiple tests on the ability to draw conclusions.
The complete statistical analysis plan will be finalized prior to database lock, and will provide statistical methods as well as descriptions
of how missing, unused and spurious data will be addressed.  Summarization of study data will be prepared of subject demographics,
baseline characteristics, and investigational product exposure.
Safety Analyses
Serious and unexpected adverse events will be collected from the time of the first study supplement administration until a subject
completes the study or discontinues prematurely. Treatment emergent adverse events (TEAEs) are defined as those AEs that develop or
worsen after the first dose of study supplement and up to 30 days beyond the last dose of study medication. The current version of
MedDRA will be used to classify all AEs.
Treatment- emergent adverse events will be summarized by System Organ Class and Preferred Term, in accordance with the MedDRA
coding dictionary. The number of subjects reporting each AE preferred term will be tabulated for all TEAEs and separately for those
considered as related to study treatment by the Principal Investigator. The number of subjects reporting SAEs will also be tabulated.
Adverse event summaries will be presented for each treatment group separately.
Adverse events will be summarized by MedDRA coding terms, and separate tabulations also will be produced for related adverse events
(those considered by the Investigator as definitively drug related), serious adverse events and discontinuations due to adverse events.
Findings from ophthalmologic examinations will be tabulated for changes over time on study. Separate summaries will be prepared for
systemic (non-ocular) and ocular AEs, with events in the study eye and non-study eye summarized separately.

IRB_00116610
- Consent Process
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
Consent Process
1. The following investigators and internal staff will obtain consent (as indicated on the Study Location and
Sponsors Page):
Susan Allman
University of Utah
Melanie Fiuza
University of Utah
Kelliann Ordonez
University of Utah
Emily Powers
University of Utah
Kelly Vorwaller
University of Utah
List by name, role, and affiliation any others who will obtain consent (e.g. Dr. John Smith, Co-Investigator, etc.).
2. Describe the location(s) where consent will be obtained.
Consent will be obtained in private research offices or clinic rooms
3. Describe the consent process(es), including the timing of consent. Describe whether there is a waiting period
between the consent process and obtaining consent from the participant (i.e., any time between informing
participants and actually obtaining consent).
If a patient appears to meet the criteria for the trial, she will be told about the study and asked for written informed
consent to participate in the trial.
If they wish to consider whether or not they want to participate in the study, they may have time to think about the study
and provide consent as long as there is enough time between approach and the gestational age required for eligibility.
4. Describe what measures will be taken to minimize the possibility of coercion or undue influence.
Research staff that conduct this consent process have been participating in research for several years. They are
experienced with obstetric study populations and will spend the time required to answer any questions or concerns. If
there appear to be concerns, the woman will be encouraged to take time to think about the study.
No additional benefits other than those described in the consent document will be discussed.
5. Describe the provisions that are made to allow adequate time to exchange information and questions between
the investigator and participant.
The research staff are experienced in interviewing and working with the obstetric population. They will be certain to take
the time needed to ensure that the person understands the study and is consenting willingly. If the woman continues to
have questions, she will also be offered the opportunity to discuss the study in further detail with the PI. She will also be
given the opportunity to return at a later time if she needs more to make a decision.
6. Will a legally authorized representative (LAR) be used?
  Yes  No
7. Will a language other than English be used to obtain consent?
  Yes  No
a. Please indicate which form will be used:
A translated short form with an English long form.

Please provide justification for why a full, translated consent document will not be used:
After the first patient is consented with the short forms, we will get the full consent form translated into the
patient’s native language and provide a translation certificate. The consent will then be submitted to the IRB via
an amendment application and the first patient will be re-consented with the fully translated ICF. Any future
patients would be enrolled with a fully translated ICF as long as it is maintained, or a short form again will be
used, and an immediate translation will take place. An interpreter will explain the clinical trial and communicate
with the patient about their potential participation. Professional translation services will be provided. It will be
documented that the patient demonstrated an understanding of the study. The interpreter will sign and date the
consent.
b. Describe whether translation services will be used for the consent process and how the consent process
will be conducted?
In the event that a participant does not speak English, the oral presentation will be translated with the use of an
interpreter. The written summary of the oral presentation will be the IRB approved long consent document.
Hospital-based, professional translation services will be provided to all non-English speaking study participants.
Consent will be documented using a short form. A third-party witness/interpreter will be present during the oral
presentation and will sign both the long form and the short form, the interpreter can act as the witness. They will
be fluent in both English and the patient’s native language. The person obtaining consent will sign the long form.
The participant will sign the short form. The participant will receive a copy of the consent form in English and the
short form.
8. Are you requesting that documentation of informed consent be waived by the IRB (a consent process in place,
but no documentation of consent, e.g. questionnaire cover letter, web-based consent, consent without
signature, etc.)?
  Yes  No
If yes, complete the following:
a. Explain why the waiver of consent documentation is being requested.
 
b. Justification for the waiver is one of the following:
There are no items to display
 

IRB_00116610
5. Data Monitoring
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
5. Data Monitoring Plan
1. Privacy Protections: Privacy refers to persons and to their interest in controlling access of others to themselves. Privacy
can be defined in terms of having control over the extent, timing and circumstances of sharing oneself (physically,
behaviorally, or intellectually) with others. What precautions will be used to ensure subject privacy is protected?
 
Select all that apply:
The research intervention is conducted in a private place
Discussing the study with participants individually instead of in front of a group
 
  Other or additional details (specify):
In order to maintain subject privacy, study personnel will not discuss genetic testing with the participant unless they are
in a private area.
2. Confidentiality Precautions: Confidentiality is an extension of the concept of privacy; it refers to the subject's
understanding of, and agreement to, the ways identifiable information will be stored and shared. Identifiable information
can be printed information, electronic information or visual information such as photographs. What precautions will be
used to maintain the confidentiality of identifiable information?
 
Select all that apply:
Storing research data on password protected computers or in locked cabinets or offices
 
  Other or additional details (specify):
Genetic testing results will not be shared with participants or included in their medical record.
3. Will photos, audio recordings, or video recordings, or medical images of participants be made
during the study?
  Yes  No
 
  If yes, describe the recording/images and what will become of them after creation (e.g.,
shown at scientific meetings, stored in the medical/research record, transcribed, erased,
etc.):
Ophthalmic images will be stored in the research record and in the electronic medical record.
4. How will study data and documentation be monitored throughout the study?
 
Select all that apply:
Periodic review and confirmation of participant eligibility
Periodic review of informed consent documentation
Periodic review of the transfer/transcription of data from the original source to the research record
Confirmation that all appropriate information has been reported to the sponsor, oversight agencies (such as the FDA),
and/or IRB
 
  Other additional details (specify):
5. Who will be the primary monitor of the study data and documentation?
 
Select all that apply:
Study Coordinator or Research Nurse
Data (and safety) Monitoring Board or Committee

 
  Other or additional details (specify):
6. How often is study data and documentation monitoring planned (e.g., monthly, twice a year,
annually, after N participants are enrolled, etc.)?
Data monitoring will occur every 3 months.

IRB_00116610
6. Risks and Benefits
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
 
6. Risks and Benefits
1. Describe the reasonable foreseeable risks or discomforts to the participants:
Risks of Carotenoid and Control Supplements – Both kinds of supplements are within the standard of care expectant mothers would
receive if they were not in the study.  They pose no additional risk to participants.
Risks of Visual acuity and contrast sensitivity – These are routine vision tests and pose no risk to participants above standard medical
care.
Risks of Ophthalmic imaging – Light levels projected on the retina during the photographs and macular pigment measurements are well
within established safety limits.  Participants may notice a central dark spot in their vision similar to the afterimage generated by a camera
flash.  This will fade in about 5 minutes.  Infants may experience discomfort during the macular pigment imaging and foveal imaging. 
Parents may feel emotional distress when observing the infant undergoing this safe examination.
Risks of Carotenoid skin measurements – There are no expected risks from the light exposure from the skin measurement.  It is
important not to look directly at the laser for a long period of time.
Risks of Blood draws – Whenever possible the blood samples for this study will be taken at the same time participants are having blood
drawn for routine prenatal blood work.  The blood sample from the infants umbilical cord will be taken at the same time blood is collected for
his/her routine care.
Risks of Eye exams – The dilation drops used for the exams are considered standard of care for dilated eye exams during pregnancy.
Risks of Nutrition surveys and supplement logs – recording diet and supplement intake will take a few minutes of participants time, but
poses no risk.
Risks of genetic research and sample banking - There is a potential risk of loss of confidentiality, but procedures are in place to make
this highly unlikely.
Unforeseeable Risks - In addition to the risks listed above, participants may experience a previously unknown risk of side effect.
2. Describe the potential benefits to society AND to participants (do not include compensation):
Participants may not directly benefit from participating in this study. Participants may receive nutritional benefits from taking the
supplements.  We hope the information we learn from this study will help us provide better care for pregnant mothers and their infants in the
future.
3. Are there any costs to the participants from participation in research?
  Yes  No
 
 
If yes, specify:
4. Is there any compensation to the participants?
  Yes  No
 
a.
If yes, answer the following:
Specify overall amount:
$125.00
 
b. Specify when participants will be paid (e.g. at each visit, at end of study, etc.):
At each study visit.
 
c. If applicable, please specify payment by visit or other time interval (e.g. $10 per visit, etc.):
$25.00 for the first 3 study visits. $50 for the final study visit.
 
d. If applicable, explain plan for prorating payments if participant does not complete the study:
Participants will be paid for each study visit they complete.

IRB_00116610
7. HIPAA & the Covered Entity
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy: Ocular
and Systemic Effects
 
 
7. HIPAA and the Covered Entity
1. Does this study involve Protected Health Information (PHI) or de-identified health
information?
  Yes  No
a. Select the method(s) of authorization that will be used:
(Consent and) Authorization Document
Waiver or Alteration of Authorization
De-identified
Select the method of de-identification:  Safe Harbor De-Identification
b. Will PHI be disclosed outside the Covered Entity?
  Yes  No
To whom?
The NEI and the FDA
And for what purposes?
For oversight of the study
Does this study involve any of the following:
2. The investigational use of a drug?
  Yes  No
3. The investigational use of a medical device?
  Yes  No
4. Is this an investigator-initiated drug or device trial lead by the Principal Investigator?
  Yes  No
5. Exposure to radioisotopes or ionizing radiation?
  Yes  No
6. A Humanitarian Device Exemption (HDE)?
  Yes  No
7. Genetic testing and/or analysis of genetic data?
  Yes  No
8. Creating or sending data and/or samples to a repository to be saved for future research
uses?

  Yes  No
9. Are you:
Collecting samples of blood, organs or tissues from participants for research purposes;  
Introducing Recombinant or Synthetic Nucleic Acids (e.g. viral vectors, oligonucleotides) or cells
containing recombinant nucleic acids (e.g. CAR-T) into participants; OR  
Introducing other biological materials (e.g. bacteria, viruses) into participants.  
  Yes  No
10. Does this study involve any of the following?
Cancer Patients
Cancer Hypothesis
Cancer risk reduction
Cancer prevention
  Yes  No
11. Any component of the Clinical and Translational Science Institute (CTSI)?
  Yes  No
The Clinical Research Center (CRC)?
  Yes  No

IRB_00116610
- Request for Waiver of Authorization
IRB_00116610
Created: 10/1/2018
12:13 PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy:
Ocular and Systemic Effects
 
Request for Waiver or Alteration of Authorization
 
Request for Waiver of Authorization for Recruitment Only
This option must only be used if you are reviewing PHI in order to identify eligible participants BEFORE approaching them to obtain consent and
authorization.  All other waiver requests must be entered below.
Waiver of Authorization for Recruitment Requested
Other Requests for Waivers of Authorization:
 
Click "Add" below to add a new waiver request to this application.
Click the waiver name link to edit a waiver that has already been created.
To delete a waiver request, contact the IRB.
  Date Created
Type of Request
Purpose of Waiver Request
There are no items to display

IRB_00116610
Waiver of Authorization for Recruitment Only
IRB_00116610
Created: 10/1/2018
12:13 PM
 
PI: Paul
Bernstein M.D.
Submitted:
11/21/2018
 
Title: Lutein & Zeaxanthin in Pregnancy (L-
ZIP) - Carotenoid Supplementation During
Pregnancy: Ocular and Systemic Effects
 
Request for Waiver or Alteration of Authorization
Request for Waiver of Authorization for Recruitment Only
 
The PI must agree to the terms of this waiver request as described on this page. 
When the PI uses the “Submit” activity to submit the application for IRB review, a
checkbox to accept the terms will be available in the “Submit” activity window.
This waiver request includes justification for waivers of consent for recruitment
only, according to 45 CFR 46.116(d).
 
Terms for the Waiver of Authorization:
 
·       The purpose of this waiver of authorization is to allow for the use of PHI in
order to identify and recruit individuals who may be eligible to participate in
the specific research described in this IRB application.  The waiver of
authorization is necessary to accommodate this minimal-risk research
activity prior to seeking a full authorization from research participants.
·       Methods for identifying individuals may include the following:
o   Reviewing medical charts
o   Reviewing databases that include PHI
o   Reviewing other medical- or health-based documents that include PHI
·       Identifiable information used under this waiver may include the following, as
this is the minimum necessary for identifying eligible individuals:
o   Name
o   Contact information, such as phone number, address, or email address
o   An ID number, such as MRN or SSN
o   Date of birth
o   Medical and health information that may determine study eligibility
·       Any PHI recorded by the study team will only be used for recruitment and
determining study eligibility.  After this has been completed, the PHI must be
removed from the research record or destroyed, unless the participants have
given authorization for continued use of the PHI.
·       PHI will only be viewed by approved members of the study team and will not
be disclosed for research purposes to any individual or institution without the
participants’ authorization for such use and disclosure of the PHI.
·       PHI will be stored in a secure manner according to HIPAA privacy and
security provisions.

IRB_00116610
- Safe Harbor De-Identification Agreement
IRB_00116610
Created: 10/1/2018
12:13 PM
 
PI: Paul
Bernstein M.D.
Submitted:
11/21/2018
 
Title: Lutein & Zeaxanthin in Pregnancy (L-
ZIP) - Carotenoid Supplementation During
Pregnancy: Ocular and Systemic Effects
 
 
Safe Harbor De-Identification
1. This declaration applies to the following part(s) of this study:
A. All of the information used
or disclosed in this study.
 
B. 
The information received or
collected from these
sources:
C. 
The information shared with
or disclosed to these
groups:
Tufts University, NYU Langone
2. As the principal investigator for this study, I declare the following:
1. To the best of my knowledge, the information could not be used (alone or with other information) to identify an
individual who is a subject of the information, and
2. None of the following types of information, regarding subjects or relatives, employers, or household members of
subjects, are used or disclosed in the part of this study indicated above:
a. Names;
b. All geographic identifiers except state or the first three digits of a zip code (however, all data from the following
17 3-digit zips are combined together under "000": 036, 059, 063, 102, 203, 556, 692, 790, 821, 823, 830, 831,
878, 879, 884, 890, and 893)
c. The month and day (the year can be kept) from all dates directly related to an individual, including birth date,
admission date, discharge date, date of death. Ages over 89 are combined in a single category of "Age 90 and
older."
d. Telephone numbers;
e. Fax numbers;
f. Electronic mail addresses;
g. Social security numbers;
h. Medical record numbers;
i. Health plan beneficiary numbers;
j. Account numbers;
k. Certificate/license numbers;
l. Vehicle identifiers and serial numbers, including license plate numbers;
m. Device identifiers and serial numbers;
n. Web Universal Resource Locators (URLs);
o. Internet Protocol (IP) address numbers;

p. Biometric identifiers, including finger and voice prints;
q. Full face photographic images and any comparable images; and,
r. Any other unique identifying number, characteristic, or code, except as permitted for re-identification.
3. If I assign a code or other means of record identification to allow de-identified information to be re-identified,
1. The code or other means of record identification is not derived from or related to information about the individual
and is not otherwise capable of being translated so as to identify the individual, and
2. I will not use or disclose the code or other means of record identification for any purpose other than re-identification,
and I will not disclose the mechanism for re-identification.
4. Before I allow a code to be used to re-identify this information,
1. If the purpose of the re-identification is within the scope of the original protocol, I will obtain approval of an
amendment from the IRB and comply with the requirements of HIPAA; or
2. If the purpose of the re-identification is outside the scope of the original protocol, I will submit a full New Study
Application, obtain IRB approval, and comply with the requirements of HIPAA.

IRB_00116610
- Investigational Use of a Drug
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy: Ocular
and Systemic Effects
 
 
Investigational Use of a Drug
#1: Complete this column if an investigational new
drug (IND) number is required.
 
#2: Complete this column if you believe an IND is
not required.
A. Provide IND Number(s):
IND #
Drug name
IND Holder
141801 DHA Softgels
Paul Bernstein, MD, PhD
A: Drug name:
B. Attach verification of the IND number to
the documents and attachments page. 
Please check the method by which you
choose to verify the IND number:
FDA letter (this is the actual letter sent to the holder of
the IND with the number)
B. Select one:
 
C. Check all of the following that that
apply:
There are no items to display
 
Statement of Compliance
The use of investigational drugs in facilities covered by the University of Utah IRB must follow the policies and procedures of the
facility in which the drug(s) will be administered and/or dispensed.
University of Utah Hospitals
If you are conducting inpatient research at the University Health Center or Huntsman Cancer Hospital, please review the Department
of Pharmacy Policies and Procedures and contact the appropriate investigational pharmacist listed below.
University of Utah Hospitals & Clinics Investigational Pharmacy: (801) 585-0272
Primary Children's Hospital
If you are conducting inpatient or outpatient research at Primary Children's Hospital, please contact the investigational pharmacist at
the number listed below:
Primary Children's Hospital - (801)662-2655
Veteran Affairs Medical Center
If you are conducting inpatient or outpatient research at the VA, please contact the investigational pharmacist at the number listed
below:
Veteran Affairs Medical Center - (801)582-1565 ext. 1454
The PI must agree to the Statement of Assurance when the PI uses the "Submit" activity to submit the application for IRB review. In
the "Submit" activity window, a checkbox to accept this Statement of Assurance will be available. By checking the box, the PI agrees
to the following:
I have read and I understand the above information provided.

I have reviewed the appropriate policies and procedures and/or have contacted the appropriate
investigational pharmacist for my research involving an investigational agent.
I understand the requirements regarding the distribution, storage, and control of investigational agent(s) for
research purposes.

IRB_00116610
- - Investigational Drug Data Form
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy:
Ocular and Systemic Effects
 
Investigational Drug Data Form
 
Drug Name
Drug Accountability
Drug Supply Location
View
Lutein-2mg
Zeaxanthin
Softgels
The Kemin softgels will be stored in and dispensed by the
Moran Eye Center Pharmacy.
The prenatal multivitamin tables will be stored in the Moran
Eye Center Clinical Studies Storage room and dispensed by
the study coordinator.
The softgels and multivitamins will only be accessible to
authorized and trained staff members.
Moran Eye Center Pharmacy and
Moran Eye Center Clinical Studies
Storage Room

IRB_00116610
Smart Form
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
Investigational Drug Data Form
1.
Name of Investigational Drug:  Lutein-2mg Zeaxanthin Softgels
2.
Synonyms:
Softgel containing 10 mg lutein, 2 mg zeaxanthin, and safflower oil.
3.
Manufacturer or Other Source:  Kemin Health, Des Moines, IA
4.
Other Study Drugs:
Placebo softgel (Kemin Health) containing safflower oil (control group will
receive).
Prenatal vitamins (all participants will receive)
5.
Type of Study (Blinding Information):
Double-masked
6.
Strength(s) and Dosage Form(s):
The active study supplement, Kemin Health Lutein-2mg Zeaxanthin softgel, is a
commercially available, over the counter product containing 10 mg of lutein and
2 mg zeaxanthin per softgel.
7.
Indications for Use and Pharmacology:
Nutritional supplement
8.
Possible Side-Effects/Adverse Reactions:
Kemin Health softgels with Lutein/zeaxathin are within the standard of care
expectant mothers would receive if they were not in the study.  There are no
expected physical risks associated with the supplements.
9.
Drug Administration Information
 
a. Usual Therapeutic Dose:
1 softgel per day (10 mg lutein, 2 mg zeaxanthin)
 
b. Dosage Range:
1 softgel per day
 
c. Therapeutic Blood Levels:
unknown (not routinely tested in standard care)
 
d. Route of Administration:
Oral
 
e. Rate of Administration for IV Infusion or Push:
N/A
 
f.
Reconstitution Directions (include stability info):
N/A
 
g. Precautions and Special Instructions for Administration:
During pregnancy and lactation take one softgel daily with food.
 
h. Toxicology and Antidote:
There are no known toxic effects of taking too much zeaxanthin. Very large
doses of carotenoids such as lutein and zeaxanthin can cause
carotenodermia - a yellow-orange skin discoloration. It can look like jaundice,
but the abnormal skin color can be removed with an alcohol swab. In case of

overdose do not induce vomiting. Contact Poison Control, physician or
pharmacist for advice.
10. Describe the plan to control, store, and dispense the
investigational drug. This plan should ensure that the drug is
only used by qualified investigator(s) for the participants
enrolled in this research project.
The Kemin softgels will be stored in and dispensed by the Moran Eye Center
Pharmacy.
The prenatal multivitamin tables will be stored in the Moran Eye Center Clinical
Studies Storage room and dispensed by the study coordinator.
The softgels and multivitamins will only be accessible to authorized and trained
staff members.
11. Location of Drug Supply:
Other
 
Moran Eye Center Pharmacy and Moran Eye Center Clinical Studies Storage
Room
12. Storage Requirements:
Room Temperature
 
 
If Other, Please Explain:
Store with cap secured at room temperature. Avoid extreme temperatures.
13. Emergency Drug Information (include name and phone
number):
Paul Bernstein, MD, PhD
801-581-4069

IRB_00116610
- Investigational Use of a Device
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy:
Ocular and Systemic Effects
 
 
Investigational Use of a Device
 
1. What is the initial risk determination of the device study according to the investigator and/or
sponsor?
The study is a non-significant risk (NSR) device study.
 
a. Provide IDE (or HDE) Number(s) for significant risk devices:
IDE #
Device Name
IDE Holder
There are no items to display
 
b. Attach verification of the IDE number for significant risk devices to the Documents and
attachments page.  Please check the method by which you choose to verify the IDE number:
There are no items to display
2. Describe the plan to control, store, and dispense the investigational device. This plan should
ensure that the device is only used by qualified investigator(s) for the participants enrolled in
this research project.
There are two investigational devices being used in this study. The first is the Heidelberg MOPD module software
program used to analyze carotenoid levels in the macula, the second is the skin scanner. Dr. Bernstein personally
oversees the use of the Heidelberg system. He does not allow use of the software program for routine medical care. Dr.
Bernstein is a patent holder for the scanner and personally control access to the scanner and train study staff in it's use.
He does not allow use of the skin scanner for routine medical care, nor would it be relevant to standard care.

IRB_00116610
- - Non Significant Risk Device
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy: Ocular
and Systemic Effects
 
 
Non-Significant Risk Device
Review the following definition of a non-significant risk (NSR) device:
1. The medical device is not a significant risk device, because all of the following are true:
a. The medical device is NOT intended as an implant that presents a potential for serious risk to the health, safety, or
welfare of a subject.
b. The medical device is NOT purported or represented to be for a use in supporting or sustaining human life that
presents a potential for serious risk to the health, safety, or welfare of a subject.
c. The medical device is NOT for a use of substantial importance in diagnosing, curing, mitigating, or treating
disease, or otherwise preventing impairment of human health that presents a potential for serious risk to the
health, safety, or welfare of a subject.
d. The medical device is does NOT otherwise present a potential for serious risk to the health, safety, or welfare of a
subject.
2. The medical device is not banned.
1. Provide justification of why the investigational medical device used in this study meets the
definition of a NSR device. 
In this study, we are using the Heidelberg MultiColor Spectralis instrument to measure and image macular pigment optical
density (MPOD). This commercial device is FDA cleared for use in eye clinics throughout the United States to image the
retina in various ways. Heidelberg has provided us with a beta version of a software package which analyzes
autofluorescence images to measure MPOD. Since this software has not yet been submitted to the FDA for approval, we
can use it only under an IRB approved protocol. This software analyzes collected images in a new way, but the actual
collection of the images is done in the usual manner for the instrument, so there are no significant risks of harm to the
subjects.
The resonance Raman skin scanner measures carotenoids in the skin by shining a blue light on the palm of the hand for
about 30 seconds. It is a higher sensitivity research version of the commercially available BioPhotonic scanner made by
NuSkin/Pharmanex. The laser power is less than many laser pointers and is completely safe for prolonged skin exposure,
so it poses no significant risk to the subjects.
 

IRB_00116610
- Genetic Research
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
Genetic Research
1. Describe the risks to participants in regard to genetic testing, including applicable risks to privacy and
confidentiality, as well as psychological and social risks.
Risks of Carotenoid and Control Supplements – Both kinds of supplements are within the standard of care expectant mothers would
receive if they were not in the study.  They pose no additional risk to participants.
Risks of Visual acuity and contrast sensitivity – These are routine vision tests and pose no risk to participants above standard
medical care.
Risks of Ophthalmic imaging – Light levels projected on the retina during the photographs and macular pigment measurements are
well within established safety limits.  Participants may notice a central dark spot in their vision similar to the afterimage generated by a
camera flash.  This will fade in about 5 minutes.  Infants may experience discomfort during the macular pigment imaging and foveal
imaging.  Parents may feel emotional distress when observing the infant undergoing this safe examination.
Risks of Carotenoid skin measurements – There are no expected risks from the light exposure from the skin measurement.  It is
important not to look directly at the laser for a long period of time.
Risks of Blood draws – Whenever possible the blood samples for this study will be taken at the same time participants are having
blood drawn for routine prenatal blood work.  The blood sample from the infants umbilical cord will be taken at the same time blood is
collected for his/her routine care.
Risks of Eye exams – The dilation drops used for the exams are considered standard of care for dilated eye exams during pregnancy.
Risks of Nutrition surveys and supplement logs – recording diet and supplement intake will take a few minutes of participants time,
but poses no risk.
Risks of genetic research and sample banking - There is a potential risk of loss of confidentiality, but procedures are in place to
make this highly unlikely.
Unforeseeable Risks - In addition to the risks listed above, participants may experience a previously unknown risk of side effect.
2. Describe the privacy protections in place for participants in regard to genetic testing. This includes how
family member privacy will be protected.
In order to maintain subject privacy, study personnel will not discuss genetic testing with the participant unless they
are in a private area.
3. Are you performing whole genome or whole exome sequencing?
  Yes  No
4. Describe the confidentiality protections in place for participants’ genetic information. Discuss if and how
data will be shared and protected outside the local study team.
Genetic testing results will not be shared with participants or included in their medical record.
5. Will incidental findings relevant to individuals or families be communicated to the participants?
  Yes  No
If yes, answer the questions below:
a. Describe the process for determining which incidental findings will be returned to the participants.
Describe the information and expert consultation that will be used to make this determination.
b. Indicate the process that will be used to return information about incidental finding to participants:
There are no items to display
If Other, describe and justify the process that will be used:
6. Will genetic information or samples be submitted to a national or international database
because of this research?
 
Yes

No

IRB_00116610
- Data & Tissue Banking
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic
Effects
 
 
Data & Tissue Banking
 
1. Select the items that will be banked:
Biological samples
Data
Type(s) of samples to be collected:
Blood, saliva and placenta tissue
2. What type(s) of future research will be allowed on the data/samples? Saliva and blood samples will be used for
research related to the genetics of carotenoid metabolism.
Placenta samples will be used to study maternal-infant carotenoid transport on a tissue level.
3. Who manages the repository and where will the data/samples be stored?
Dr. Bernstein at the Moran Eye Center.
4. Indicate whether the data/samples in the repository will be identifiable directly or through a code/link.
 
a. Select one of the following options:
OPTION 1: All data/samples will be identifiable to one or more individuals who have responsibilities to
manage or oversee the repository.
 
 
  b. If you selected OPTION 1 or 2 above, describe the process for managing the identifiable data:
    Who will manage and have access to the identifiable data?
Dr. Bernstein and the Utah study team.
    Where will the data be kept?
On paper study records, in the RedCap database created for this study and on University maintained computer
servers.
    How will the data be kept confidential?
The study team will protect study data according to HIPAA regulations and prohibit access to anyone who does
not need the information in order to perform their job.
 
 
5. Describe the procedures for participants to withdraw their data/samples from the repository. If
participants will not be able to withdraw their samples, please provide an explanation:
Participants will need to contact Dr. Bernstein or a member of the study team and request their sample be withdrawn.
6. Will future research results or findings be communicated to the participants?
  Yes  No
 
 
7. Describe the procedures for other researchers to obtain data/samples from the repository for use in future
research.
Other researchers will need to provide proof of IRB approval for their project and an executed material transfer
agreement, if applicable.

IRB_00116610
8. Resources and Responsibilities
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy:
Ocular and Systemic Effects
 
 
8. Resources and Responsibilities
1. * State and justify the qualifications of the study staff:
Study physicians have a medical license allowing them to make medical decisions and provide patient care.  They are qualified by
certification and experience to conduct the study.
Study Coordinators have experience in conducting clinical studies and receive protocol specific training from the sponsor, investigator and
other study team members.
  
 
2. * Describe the training that study staff and investigators will receive in order to be informed
about the protocol and understand their research-related duties and functions:
Study specific training includes face to face training such as Investigator meetings or staff meetings, e-mail correspondence,
webinars/teleconferences.  All study staff members and investigators agree to conduct the study according to good clinical practices and
the ethical conduct of research.  Training documentation, including but not limited to study meetings, GCP certificates and CITI certificates
will be maintained in the study file.
3. * Describe the facilities where the research activities will be performed (e.g. hospitals,
clinics, laboratories, classrooms/schools, offices, tissue banks, etc.).
Study visits will take place at the University of Utah hospital, Well Baby Nursery, OB/GYN outpatient clinic and Moran Eye center clinic.
Study procedures and data collection will be conducted by staff from the OB/GYN department and the Moran Eye Center at the University
of Utah.  
The study outcome data will be analyzed by a consultant from the University of Utah Study Design and Biostatistics Center of the Center
for Clinical and Translational Science.
Image analysis of retinal camera macular pigment measures will be conducted in Dr. Bernstein’s laboratory.
De-identified data (nutrition surveys) will be sent to Tufts University under an MTA.  The MTA will be signed an kept with the research
records.
De-identified placenta samples will be sent to NYU Langone for analysis under an MTA.
4. * Describe the medical or psychological resources available at this site (and other
participating sites, if applicable) that participants might require as a consequence of the
research. If not applicable, please state.
Medical resources at the Moran Eye Center and University of Utah Hospital and Clinics are available to treat any complications of the
participants' eye conditions related to their participation in the research.  The PI and the sub-investigators are always available to answer
any questions that the participants may have and have the expertise to handle any medical issues that may arise.

IRB_00116610
Documents and Attachments
IRB_00116610
Created: 10/1/2018 12:13
PM
 
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) -
Carotenoid Supplementation During Pregnancy: Ocular
and Systemic Effects
 
Documents and Attachments
If any of your documents (such as investigational brochures, sponsor protocols, advertisements, etc.) are not available in an electronic format, please scan
and save them as PDF files or contact our office for assistance.
Naming Documents: Please use the title field to clearly indicate the content of each form. The name you enter will be listed on your approval letter. Use
names that will differentiate from earlier versions.
Examples:
Consent Document Control Group 04/14/05
Consent Document Treatment Group 4/14/05
Sponsor Protocol 04/14/05 Version 2
Assent Document(Highlighted Changes)
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Print View: IRB Draft Protocol Summary
eProtocol Summary:
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Th
it
t
di
l

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Grant Application:
The Federal Government is a direct or indirect sponsor of your research. You are required to provide a copy of the grant
proposal, grant award, or sub-award.
By submitting to the IRB, you are confirming the grant and the study protocol are consistent (Design, Study Population,
Study Objectives and Goals, Test Interventions and Procedures, etc.)
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Literature Cited/References:
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Principal Investigator's Scholarly Record (CV/Resume):
Name
VersionDate Created
Date Modified
Date Approved
Bernstein CV 13 May 2015.pdf(0.01)
0.01
5/14/2015 1:10 PM 5/14/2015 1:10 PM  
Bernstein CV 13 Sep 2017.pdf(0.01)
0.01
1/9/2018 3:49 PM
1/9/2018 3:49 PM
 
Bernstein CV exp 9.13.2021.pdf(0.01)
0.01
4/19/2021 12:42 PM4/19/2021 12:42 PM 
Faculty Sponsor's Scholarly Record (CV/Resume):
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IRB_00116610
Finish
IRB_00116610
Created: 10/1/2018 12:13 PM  
PI: Paul Bernstein M.D.
Submitted: 11/21/2018  
Title: Lutein & Zeaxanthin in Pregnancy (L-ZIP) - Carotenoid
Supplementation During Pregnancy: Ocular and Systemic Effects
 
 
Finish Instructions
 
Finish Instructions
1. To view errors, select the "Validate" option at the top-left of the page. If you have errors on your application,
you won't be able to submit it to the IRB.
2. Selecting the Finish button will NOT submit the application to the IRB.
You MUST select the "Submit" option on the workspace once you've selected the "Finish" button.
3. If your study has a faculty sponsor: Once the PI submits the application, it will be sent to the faculty sponsor
for final approval. The IRB cannot review the study until the faculty sponsor submits the application to the IRB.