Clinical trial NCT03949244
Conditions: Glaucoma, Open-Angle
Keywords: Nailfold capillary imaging Latanoprost bunod Latanoprost
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2019-08-15; Completion date: 2020-10-01
Enrollment: 47 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to look at the relationship of small blood vessels irregularities observed with an imaging system called video nailfold capillaroscopy in people with primary open-angle glaucoma. Nailfold capillaroscopy (NFC) is a video camera with a magnifying lens used for studying the movement of blood in small blood vessels. It is simple, safe and does not penetrate the skin. The skin fold that is at the tip of the finger is called the "nailfold". NFC has been used to assess blood vessel narrowing in patients with glaucoma.

Detailed description:
In this study, the study team investigates the effect of topically-applied latanoprostene bunod (LTB) on the blood flow at the nailfold of the 4th finger in patients with primary open angle glaucoma. LTB is a new anti-glaucoma eye drop which received FDA clearance in early November 2017. It has two components: the prostaglandin analog (PGA) which decreases intraocular pressure (IOP) by enhancing the drainage of the aqueous (the fluid in the front part of the eye) from the eye, and the nitric oxide (NO) moiety which naturally dilates arteries in the body. The capillaries at the nailfold are comparable to those of the optic nerve head, which makes them a reasonable surrogate for evaluation of the effect of LTB on the blood flow. Therefore, this study may provide indirect evidence for the beneficial effect of LTB on blood flow to optic nerve which can potentially save the optic nerve from glaucomatous damage. Primary open angle glaucoma is a progressive condition and is the most common cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is a subset of the glaucomas defined by an open, normal appearing anterior chamber angle and raised intraocular pressure (IOP), with no other underlying disease.

In addition to LTB, the study team will use latanoprost (L), an-FDA approved PGA anti-glaucoma eye drop and normal saline (NS: the physiologic solution composed of 0.9% salt and water), as controls to make sure the effects of LPB on nail fold capillary blood flow is not due to its PGA (as L is) or due to the placebo effect (as NS is).

This study may also serve as background information for the development of new anti-glaucoma medications which can be injected into the eye to facilitate blood flow to the optic nerve.

Arms: arm 1: Latanoprost 0.005% drops to the nailfold. arm 2: Latanoprost bunod 0.024% drops to the nailfold. arm 3: Normal saline 0.9% to the nailfold.
Interventions: intervention 1: Latanoprost 0.005% intervention 2: Latanoprost bunod 0.024% intervention 3: Normal saline 0.9% intervention 4: Nailfold capillaroscopy
Intervention descriptions: intervention 1: Latanoprost 0.005% will be applied to the nailfold and images of the blood flow in the nailfold capillaries will be acquired. intervention 2: Latanoprost bunod 0.024% will be applied to the nailfold and images of the blood flow in the nailfold capillaries will be acquired. intervention 3: Normal saline 0.9% will be applied to the nailfold and images of the blood flow in the nailfold capillaries will be acquired. intervention 4: An imaging system and does not penetrate the skin. A video camera with a magnifying lens used for studying the movement of blood in small blood vessels at the nailfold of the 4th finger.

Protocol documents:
Prot_SAP_000.pdf: 
Effect of Nailfold Application of Latanoprostene Bunod on Nailfold Capillary Blood Flow 
PI: Dr. James Tsai 
NCT03949244 
Document Date: 12-18-2019 


Icahn School of Medicine at Mount Sinai
Mount Sinai Beth Israel
Mount Sinai Brooklyn
The Mount Sinai Hospital
Mount Sinai Queens
New York Eye and Ear Infirmary
of Mount Sinai
Mount Sinai St. Luke's
Mount Sinai West
Program for the Protection
of Human Subjects
Institutional Review Boards
Mount Sinai Health System
One Gustave L. Levy Place, Box
 1081
New York, NY 10029-6574
T 212-824-8200
F 212-876-6789
irb@mssm.edu
icahn.mssm.edu/pphs
Initial Application
IRB-18-01336
Robert Ritch
Table of Contents
1. Summary - Title.....................................................................................................................................................................1
2. Summary - Setup..................................................................................................................................................................2
3. Summary - Background......................................................................................................................................................4
4. Research Personnel.............................................................................................................................................................6
5. Sites.......................................................................................................................................................................................... 7
6. Subjects - Enrollment.......................................................................................................................................................... 8
7. Subjects - Setting and Resources...................................................................................................................................9
8. Subjects - Populations......................................................................................................................................................10
9. Subjects - Participation.....................................................................................................................................................11
10. Subjects - Risk and Benefits........................................................................................................................................12
11. Procedures - Narrative...................................................................................................................................................13
12. Procedures - Genetic Testing......................................................................................................................................15
13. Procedures - Details....................................................................................................................................................... 16
14. Procedures - Compensation.........................................................................................................................................17
15. Consent - Obtaining Consent.......................................................................................................................................18
16. Consent - Documents.....................................................................................................................................................19
17. Data - Collection...............................................................................................................................................................20
18. Data - HIPAA.................................................................................................................................................................... 21
19. Data - Storage.................................................................................................................................................................. 22
20. Data - Safety Monitoring................................................................................................................................................24
21. Funding................................................................................................................................................................................25
22. Drugs / Biologics..............................................................................................................................................................26
23. Financial Administration................................................................................................................................................. 31
24. Attachments....................................................................................................................................................................... 32


IRB-18-01336
Initial Application
Robert Ritch
1. Summary - Title
Protocol Title
Effect of Nailfold Application of Latanoprostene Bunod on Nailfold Capillary Blood Flow
Principal Investigator
Robert Ritch
When the application is complete, it will be sent to the PI for submission
When the application is complete, it will be sent to the PI for submission
Primary Department
Ophthalmology
When the application is complete, it will be sent to the PI for submission
Application Initiated By
Harriet Lloyd
Lay Summary
In this study, we investigate the effect of topically-applied latanoprostene bunod (LTB) on the blood flow at the nail
 fold of the 4th finger in patients with primary open angle glaucoma. LTB is a new anti-glaucoma eye drop which
 received FDA clearance in early November 2017. It has two components: the prostaglandin analog (PGA) which
 decreases intraocular pressure (IOP) by enhancing the drainage of the aqueous (the fluid in the front part of the eye)
 from the eye, and the nitric oxide (NO) moiety which naturally dilates arteries in the body. The capillaries at the nail
 fold are comparable to those of the optic nerve head, which makes them a reasonable surrogate for evaluation of the
 effect of LTB on the blood flow. Therefore, this study may provide indirect evidence for the beneficial effect of LTB on
 blood flow to optic nerve which can potentially save the optic nerve from glaucomatous damage.
Primary open angle glaucoma is a progressive condition and is the most common cause of irreversible blindness
 worldwide. Primary open angle glaucoma (POAG) is a subset of the glaucomas defined by an open, normal
 appearing anterior chamber angle and raised intraocular pressure (IOP), with no other underlying disease.
In addition to LTB, we will use latanoprost (L), an-FDA approved PGA anti-glaucoma eye drop and normal saline (NS:
 the physiologic solution composed of 0.9% salt and water), as controls to make sure the effects of LPB on nail fold
 capillary blood flow is not due to its PGA (as L is) or due to the placebo effect (as NS is).
This study may also serve as background information for the development of new anti-glaucoma medications which
 can be injected into the eye to facilitate blood flow to the optic nerve.
We will recruit 120 subjects with POAG at New York Eye and Ear Infirmary of Mount Sinai.  Participation in this study
 will take approximately 60 minutes in one visit, and entails having NFC videos recorded after application of cedar oil
 and again after application of glaucoma drops, as well as having basic medical information recorded, such as height,
 weight, BMI, pulse and blood pressure.
IF Number
IF2532592
Page 1 of 32


IRB-18-01336
Initial Application
Robert Ritch
2. Summary - Setup
Funding Has Been Requested /
 Obtained
Yes
Application Type
Request to Rely on Mount Sinai IRB
Research Involves
Prospective Study ONLY
Consenting Participants
Yes
Requesting Waiver or Alteration
 of Informed Consent for Any
 Procedures
No
Humanitarian Use Device (HUD)
 Used Exclusively in the Course of
 Medical Practice
No
Use of an Investigational Device to
 Evaluate Its Safety or Effectiveness
No
Banking Specimens for Future
 Research
No
Cancer Related Research that
 Requires Approval from the
 Protocol Review and Monitoring
 Committee (PRMC).
No
   Is this Cancer Related Research?  Cancer Related Research is defined as research that
 has cancer endpoints or has a cancer population as part of or all of its targeted population.
 This includes protocols studying patients with cancer or those at risk for cancer.
  
Clinical Trial
Yes
   
   * A prospective biomedical or behavioral research study of human subjects that is
 designed to answer specific questions about biomedical or behavioral interventions
 (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). 
   *  Used to determine whether new biomedical or behavioral interventions are safe,
 efficacious, and effective.    
  
Drugs / Biologics 
Yes
   
   * Drugs / Biologics That Are Not a Part of Standard Practice 
   * Controlled Substances 
   * Drugs / Biologics Supplied by the Research Sponsor or Purchased with Study Funds 
  
   Ionizing Radiation for imaging or therapy, including X-Ray, Fluoroscopy, CT, Nuclear
 Medicine, PET andor Radiation Therapy:
  
* Purely for standard of care:
No
* In frequency or intensity that
 exceeds what is necessary for
 standard of care:
No
Hazardous Materials
No
   * Recombinant DNA 
   * Viral Vectors 


   * Plasmids 
   * Bacterial Artificial Chromosomes 
   * Toxic Chemicals, Potentially Toxic Medications, Carcinogens 
   * Autologous Cell Lines 
  
Request Use of Clinical Research
 Unit Resources
No
Page 3 of 32


IRB-18-01336
Initial Application
Robert Ritch
3. Summary - Background
Objectives
The objective of this study is to assess changes in the nail fold capillary (NFC) blood flow after nailfold (NF)
 application of Iantanoprostene bunod (LTB) in primary open angle glaucoma (POAG) patients compared to change
 in NFC blood flow after NF application of latanoprost 0.005% or saline.
Background
Nitric Oxide (NO)-mediated vasodilation in response to vascular shear stress operates via the intracellular receptor
 soluble guanylyl cyclase (sGC) stimulating production of cyclic guanosine monophosphate (cGMP) (1). Impaired NO
 signaling plays an important role in POAG. Impaired retinal arteriole (2) and brachial (3) artery autoregulation has
 been demonstrated in POAG after increased shear stress. Furthermore, reduced resting blood flow in the retina,
 choroid, and extraocular vessels exists in POAG (4-6). 
NF capillaroscopy is a noninvasive technique for in vivo imaging of capillaries near the fingernail and has a role
 in diagnosis of rheumatic conditions (7).  NFC morphological (8) and hemodynamic (9) abnormalities have been
 demonstrated in POAG. These abnormalities may be mediated in part by impaired NO signaling. LTB is a dual acting
 antiglaucoma agent that contains a PGA and a NO donator. 
Improving optic nerve head microcirculation may protect the optic nerve from glaucomatous degeneration. The
 NF microcirculation has layers of hairpin looped capillaries that are comparable to the optic nerve circulation (10).
  NF application of LTB may result in increased levels of cGMP (11) or S-nitrosylation of hemoglobin which may
 enhance conductive vasodilation (12).  We do not expect LTB applied to the NF to have an effect on optic nerve
 microcirculation; however, should intracameral delivery of LTB be developed, the data generated here may be useful
 background information for optic nerve microcirculatory studies that would ensue. 
References:
1. Buys ES, Ko YC, Alt C, Hayton SR, Jones A, Tainsh LT, et al. Soluble guanylate cyclase alpha1-deficient mice: a
 novel murine model for primary open angle glaucoma. PloS one. 2013;8(3):e60156.
2. Feke GT, Pasquale LR. Retinal blood flow response to posture change in glaucoma patients compared with
 healthy subjects. Ophthalmology. 2008;115(2):246-52.
3. Fadini GP, Pagano C, Baesso I, Kotsafti O, Doro D, de Kreutzenberg SV, et al. Reduced endothelial progenitor
 cells and brachial artery flow-mediated dilation as evidence of endothelial dysfunction in ocular hypertension and
 primary open-angle glaucoma. Acta ophthalmologica. 2010;88(1):135-41.
4. Logan JF, Rankin SJ, Jackson AJ. Retinal blood flow measurements and neuroretinal rim damage in glaucoma.
 The British journal of ophthalmology. 2004;88(8):1049-54.
5. Yin ZQ, Vaegan, Millar TJ, Beaumont P, Sarks S. Widespread choroidal insufficiency in primary open-angle
 glaucoma. Journal of glaucoma. 1997;6(1):23-32.
6. Kaiser HJ, Schoetzau A, Stumpfig D, Flammer J. Blood-flow velocities of the extraocular vessels in patients
 with high-tension and normal-tension primary open-angle glaucoma. American journal of ophthalmology.
 1997;123(3):320-7.
7. Cortes S, Cutolo M. Capillarosecopic patterns in rheumatic diseases. Acta reumatologica portuguesa.
 2007;32(1):29-36.
8. Pasquale LR, Hanyuda A, Ren A, Giovingo M, Greenstein SH, Cousins C, et al. Nailfold Capillary Abnormalities in
 Primary Open-Angle Glaucoma: A Multisite Study. Invest Ophthalmol Vis Sci. 2015(1552-5783 (Electronic)).
9. Gasser P, Flammer J. Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension
 glaucoma. American journal of ophthalmology. 1991;111(5):585-8.
10. An L, Johnstone M, Wang RK. Optical microangiography provides correlation between microstructure and
 microvasculature of optic nerve head in human subjects. J Biomed Opt. 2012;17(11):116018.
11. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of Endothelin-1-Induced
 Trabecular Meshwork Cell Contractility by Latanoprostene Bunod. Investigative ophthalmology & visual science.
 2015;56(6):4108-16.
12. Zhang R, Hess DT, Reynolds JD, Stamler JS. Hemoglobin S-nitrosylation plays an essential role in
 cardioprotection. J Clin Invest. 2016;126(12):4654-8.
Primary and Secondary Study Endpoints
We will assess change in NFC blood flow after NF application of LTB in POAG patients. This is a parallel, masked
 3-arm randomized trial consisting of normal saline, latanaprost 0.005% and LTB 0.024%. Patients will have
 baseline NFC blood flow measurements after application of cedar oil.  Then we will use NF application of either
 normal saline, latanoprost 0.005% or LTB 0.024% in random sequence.  The patient and imager will know which
 study drug is applied.  NFC blood flow will be remeasured after 15 minutes.  NF article application will occur on a


 specially designed well applied to the 4th digit of the nondominant hand.  The readers will make all NFC blood flow
 measurements in masked fashion.  
The endpoint of the study is to measure the change in NFC blood flow 15 minutes after NF application to the 4th digit
 of the nondominant hand.
The secondary endpoint is to determine if the change in NFC blood flow after LTB will be greater than the change
 seen with either normal saline or latanoprost.
Protocol Was Already Approved
 by the Icahn School of Medicine at
 Mount Sinai (ISMMS) Institutional
 Review Board (IRB) Under a
 Different Principal Investigator
No
Protocol Was Previously Submitted
 to an External(non-ISMMS) IRB
No
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IRB-18-01336
Initial Application
Robert Ritch
4. Research Personnel
Name/Department
Role/Status
CC
Access
Obtaining
 Consent
Phone
Email
Robert Ritch /
 Ophthalmology
PI / 
Yes
SIGNAUTHYes
2126735140
Ahmad Najafi /
 Ophthalmology
Co-Investigator / 
Yes
EDIT
Yes
Erica B. Jacobs /
 Ophthalmology
Study Coordinator / 
Yes
READONLYYes
Maria Scolaro /
 Ophthalmology
Study Coordinator / 
Yes
EDIT
Yes
Elena Alvarado /
 Ophthalmology
Study Coordinator / 
READONLYYes
212-477-7540
 ext 5371
Emily Seo /
 Ophthalmology
Study Coordinator / 
Yes
SIGNAUTHYes
Harriet Lloyd /
 Ophthalmology
Admin (non-FCOI) / 
Yes
SIGNAUTH
2129794672
Katy Tai /
 Ophthalmology
Admin (non-FCOI) / 
Yes
SIGNAUTH
Louis Pasquale /
 Ophthalmology
Co-Investigator / 
Yes
SIGNAUTHYes
Mark Gentile /
 Ophthalmology
Study Coordinator / 
Yes
SIGNAUTHYes
 
Page 6 of 32


IRB-18-01336
Initial Application
Robert Ritch
5. Sites
Site Name
New York Eye and Ear Infirmary of Mount Sinai
Other External Site Name
Contact Details
Approved
1
Approval Document
IRB-18-01336 approval letter.pdf
Funded By Mount Sinai
0
Reviewed By
Mount Sinai IRB
Other IRB
Site Name
Other External Site
Other External Site Name Mount Sinai Doctors - East 85th Street
Contact Details
Approved
0
Approval Document
Funded By Mount Sinai
0
Reviewed By
Mount Sinai IRB
Other IRB
Page 7 of 32


IRB-18-01336
Initial Application
Robert Ritch
6. Subjects - Enrollment
Site Name
New York Eye and Ear Infirmary of Mount
 Sinai
Subjects To Be Enrolled
120
Site Name
Other External Site
Subjects To Be Enrolled
Total Number of Subjects to be
 Enrolled Across All Listed Sites
 Above (Auto Populated)
120
Page 8 of 32


IRB-18-01336
Initial Application
Robert Ritch
7. Subjects - Setting and Resources
Setting of Human Research
Faculty Practice Associates, Clinical
 Research Unit (CRU)
Total Number of Subjects Needed
 To Complete Study
60
Feasibility of Meeting Recruitment Goals
120 Patients with primary open angle glaucoma (POAG) will be pre-screened and identified by the treating physician,
 and by searching the NYEEI medical records and collaborating with our in-house medical staff for referrals to the
 study.  The glaucoma practice at NYEEI will be able to provide a more than sufficient number of potential subjects.
Facilities To Be Used for Conducting Research
New York Eye and Ear Infirmary of Mount Sinai (NYEEIMS),    Einhorn Clinical Research Center at NYEEIMS.
Multi-Center Study
No
Community-Based Participant
 Research Study
No
  PI must attest to the following. 
   * Process is adequately described to ensure that all persons assisting with the trial are
 adequately informed about the protocol, the investigational product(s), and their trial-
related duties and functions.
     
    
Page 9 of 32


IRB-18-01336
Initial Application
Robert Ritch
8. Subjects - Populations
Inclusion Criteria
1)  40 years old to 80 years old
2)  all participants will have open angles and no signs of secondary glaucoma such as exfoliation syndrome
3)  untreated intraocular pressure (IOP) may be #21mmHg or #21mmHg in both eyes
4)  the cup-to-disc ratio (CDR) #0.6 in both eyes and CDR asymmetry #0.2.  
5)  POAG patients will have reliable Humphrey Visual Field (HVF) loss consistent with optic nerve damage
6)  POAG patients can have any stage of POAG and be on any form of treatment for their disease. 
7)  willingness to sign informed consent and comply with study procedures.
Exclusion Criteria
1)  History of non-POAG forms of glaucoma
2)  pregnancy
3)  Inability to give informed consent
Enrollment Restrictions Based
 Upon Gender, Pregnancy,
 Childbearing Potential, or Race
Yes
Justify Restriction(s)
While there have been no adverse effects of latanoprost drops on pregnant women of fetuses, we will be excluding
 pregnant women out of an overabundance of caution.  This is a pilot study with a small number of subjects being
 recruited.  No treatments or therapies are being considered in this project.
Age Range(s)
18 to 64 Years, 65 Years and Over
Targeted Population(s)
Adults - Patients 
Other Aspects that Could Increase Subjects Vulnerability
We will recruit patients from age 25 to age 80 among a population able to provide informed consent, but not recruit
 from any other vulnerable populations e.g. fetuses, neonates, pregnant women, prisoners, or institutionalized
 individuals. The risk to human subjects will be minimal, and there are no other aspects that could increase subjects'
 vulnerability.
Safeguards to protect Subjects rights and welfare
Safeguards included in this project includes the responsibility of the investigator to ensure that all regulations and
 documentation is handled in a compliant and timely manner.
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IRB-18-01336
Initial Application
Robert Ritch
9. Subjects - Participation
Duration of an Individual Subjects Participation in the Study
60 minutes during one visit.
Duration Anticipated to Enroll All Study Subjects
One year.
Estimated Date for the Investigators
 to Complete This Study
Within 5-10 years
Procedures for Subjects to Request Withdrawal
We will emphasize that subjects are free to withdraw from the study at any time without any penalty, even after
 having provided written consent/assent.  
Subjects will need to provide written withdrawal when withdrawing HIPAA authorization specifically.
Procedures for Investigator to Withdraw Subjects
The investigator and the consent will document that the subject may stop being in the research study and any
 collected data will be withdrawn.
Participants Will Be Recruited
Yes
Recruitment Method(s)
Clinical Practice
How Participants Will Be Identified
Participants will be identified by their treating physician as having met the inclusion/exclusion criteria. They will also
 be identified by searching the NYEEI medical records and collaborating with our in-house medical staff for referrals
 to the study. Eligible patients for recruitment will be screened for by the doctor. The charts may be earmarked for
 recruitment on the day of their visit. 
Who Will Initially Approach
 Potential Participants
Treating Physician
How Research Will Be Introduced to Participants
The research projects will be introduced to potential subjects by the treating physician. If participants are interested
 then the treating physician will call the study staff and formally introduce each other.  The study staff will  approach
 the potential participant to explain the study and obtain consent. 
How Participants Will Be Screened
Research procedures will take place only after subjects have provided their consent to participate. All subjects will
 receive a complete eye examination ETDRS visual acuity, refraction, slit lamp and dilated fundus examination will be
 performed to evaluate whether the subject will be eligible based on the inclusion & exclusion criteria. 
We will also obtain baseline height, weight, blood pressure, pulse, and NF capillaroscopy (which requires placing a
 drop of cedarwood oil on the cuticle to facilitate visualization) pre-intervention.  
Page 11 of 32


IRB-18-01336
Initial Application
Robert Ritch
10. Subjects - Risk and Benefits
Risks to Subjects
There are no essential risks to the subjects. LTB is an FDA-approved drug with essentially no systemic side effects.
 NF capillary drug application is equivalent to taking a single ocular dose of medicine that delivers 0.76 micrograms of
 drug to a volume of circulation of 70 liters. 
Risks of application of cedarwood oil:  A very rare but potential effect of mild irritation when applying cedar essential
 oil to the skin has been reported.
Risks of LTB and Latanoprost:  There is also the remote possibility that the glaucoma drops could cause an allergic
 reaction or cause irritation to the nailfold, both of which would result in redness and itching and would be easily
 treated by washing the affected area with soap and water.
Description of Procedures Taken to Lessen the Probability or Magnitude of Risks 
The research team that has been assembled has sufficient expertise and experience to conduct the research.  The
 inclusion/exclusion criteria will allow us to enroll only the desired population of interest. The experimental procedure
 will take place while the subject is here for their standard of care examination.  Data will be stored in such a way that
 it is impossible to connect research data directly to the
individuals from whom or about the data pertain. Access to key codes will be limited and stored separately from the
 data.
Provisions for Research Related Harm / Injury
In case of injury due to the study, the investigator will be alerted and medical care will be provided.  Care for such
 injury will be billed in the ordinary manner to the subject.
Expected Direct Benefit to Subjects
There are no expected direct benefits to subjects. This is a proof of principle study to demonstrate that LTB may have
 acute microculatory effects.
Benefit to Society
The benefit from the data obtained may be useful scientifically and we hope to learn from this study which will
 potentially benefit the patients in the future
Provisions to Protect the Privacy Interests of Subjects
The investigator will establish ahead of time what de-identified information will be revealed to whom and under what
 circumstances, and will communicate these provisions to protect the privacy interests of the subjects in a clear
 language through the informed consent process. 
Authorized medical release forms will be requested from the subject should they decide to dictate whom is allowed to
 view their results.
In all disclosures outside of Mount Sinai, subjects will not be identified by name, social security number, address,
 telephone number, or any other direct personal identifier unless disclosure of the direct identifier is required by law.
 Some records and information disclosed may be identified with a unique code number.
Economic Impact on Subjects
All research procedures will be paid for by the study.  Being in this research study will not lead to extra costs for the
 subject.
Page 12 of 32


IRB-18-01336
Initial Application
Robert Ritch
11. Procedures - Narrative
Description of the Study Design
We will assess change in NFC blood flow after NF application of LTB in POAG patients. This is a parallel, masked 3-
arm randomized trial consisting of normal saline, latanaprost 0.005% and LTB 0.024%. 
Description of Procedures Being Performed
Patients will be consented prior to any study-related interventions. Patients will have baseline NFC blood flow
 measurements after application of cedar oil.  Then we will use NF application of either normal saline, latanoprost
 0.005% or LTB 0.024% in random sequence.  The patient and imager will know which study article is applied.  NFC
 blood flow will be remeasured after 15 minutes.  NF article application will occur on a specially designed well applied
 to the 4th digit of the non-dominant hand.   
We believe that the same capillaries will be visualized before and after treatment, due to the limited width of the
 fingertip. The procedure for NFC videography is to sample consecutive capillaries, pausing on each capillary until
 blood flow was visualized. If no blood flow is visualized after 10 seconds in focus, the immediate medial capillary
 is assessed in similar fashion. Blood flow for 10 seconds on each of the first five visible capillaries is captured. We
 believe that this method will allow us to capture flow in the same capillaries pre- and post-treatment.
We will measure pulse and blood pressure at baseline and after NF drug application for safety purposes. We will also
 collect height and weight in order to adjust for body mass index in our analyses.
The readers will make all NFC blood flow measurements in masked fashion. 
We will assess change in NFC blood flow after NF application of LTB in POAG patients. This is a parallel, masked 3-
arm randomized trial consisting of normal saline, latanaprost 0.005% and LTB 0.024%. Patients will have baseline
 NFC blood flow measurements after application of cedar oil.  Then we will use NF application of either normal saline,
 latanoprost 0.005% or LTB 0.024% in random sequence.  The patient and imager will know which study article is
 applied.  NFC blood flow will be remeasured after 15 minutes.  Preliminary data on controls suggests that 15 minutes
 is sufficient time to see a change in blood flow.   NF article application will occur on a specially designed well applied
 to the 4th digit of the non-dominant hand.  Two masked observers will evaluate NFC blood flow using the method
 described below.
Description of Nailfold Video Capillaroscopy:
A BK-XW880 nailfold video capillaroscope at 300x magnification (Biobase Meihua Trading Co., Jinan, Shandong,
 China) will be used to image nailfold capillaries. Cedarwood oil is applied to the finger skin to achieve adequate
 focus. The subject orients their hand in the prone position and the lateral-most edge of the nailfold of the fourth
 finger of the non-dominant hand is imaged. We chose this sampling protocol to minimize the effect of local trauma
 on nailfold capillary hemodynamics.  Consecutive capillaries are sampled, pausing on each capillary until blood flow
 is visualized. If no blood flow is visualized after 10 seconds in focus, the immediate medial capillary is assessed
 in similar fashion. Blood flow for 10 seconds on each of the first five visible capillaries is captured. This method is
 repeated pre- and post-NF article application. 
Nailfold videos are converted to image sequences and imported into ImageJ software (National Institutes of Health,
 Bethesda, MD) to measure blood speed, diameter, and flow. Each capillary is cropped out of the image sequence
 spanning the duration of visible blood flow for the given capillary. The cropped image sequence is registered using
 StackReg, an open-source ImageJ plugin. Two readers masked to case status will validate the measurement
 methods. Because morphological abnormalities such as tortuosity and hemorrhaged capillaries are present in POAG
 and morphology may affect resistance to blood flow within the vessel, a straight segment of the capillary is used for
 analysis. Each reader will track the first visible void in the blood column between the first pair of consecutive frames
 in which the blood column void is clearly defined in both frames as performed in other studies. The time elapsed
 between consecutive frames is calculated based on the frame per second rate of the video (25 frames per second).
 The distance in microns covered by the blood column void is divided by the reciprocal of the frames per second rate
 to generate blood speed in microns per second. Each reader will also measure diameter of the vessel in the vicinity
 of the blood column void. Assuming a circular geometry for the lumen on the vessel, the cross-sectional area of the
 vessel is then calculated. Capillary blood flow is calculated by multiplying blood speed by cross-sectional area of the
 vessel.
Description of the Source Records that Will Be Used to Collect Data About Subjects 
All data collected will be primary source data.  We will collect the diagnosis of POAG from the subject's electronic
 medical record. We will obtain medical history data from electronic charts as well.  Interventional data that will be


 collected specifically for this project include NF capillaroscopy, blood pressure and pulse readings, which will be
 performed by the imager and recorded in an electronic data file using de-identified subject id numbers.
Description of Data that Will Be Collected Including Long-Term Follow-Up
1. Obtain baseline height, weight, blood pressure, pulse.  
2. Perform NF capillaroscopy (including placing a drop of cedarwood oil on the patient's cuticle) pre-intervention. 
3. Obtain blood pressure, pulse, and NF capillaroscopy 15 minutes after intervention.
4.     Obtain medical history from electronic chart after visit: age, sex, ancestry, body mass index, baseline blood
 pressure, baseline pulse, hypertension (yes/no), diabetes mellitus (yes/no), current smoker (yes/no), use of
 antiplatelet or anticoagulant, maximum known IOP, current IOP, current cup-disc ratio, current mean deviation and
 pattern standard deviation from worse eye from the latest reliable Humphrey visual field test.
There will not be any long-term followup for this study.
Research Requires HIV Testing
No
Page 14 of 32


IRB-18-01336
Initial Application
Robert Ritch
12. Procedures - Genetic Testing
Genetic Testing Will Be Performed
No
Guidance and Policies > Future Use Data Sharing and Genetic Research
  
Page 15 of 32


IRB-18-01336
Initial Application
Robert Ritch
13. Procedures - Details
Surveys or Interviews
No
Audio / Photo / Video Recording
Yes
Subjects Will Be Identifiable
No
Media Will Be Discarded When the
 Research Study is Completed
Yes
How Media Will Be Stored to Ensure Confidentiality
Data is coded with Subject study ID and stored on the PI's password protected file and password protected computer.
Media Will Be Shared with Others
No
Audio / Photo / Video Recording is
 Required for Participation
Yes
Deception
No
Results of the Study Will Be Shared
 with Subjects or Others
Yes
How the Results Will Be Shared
Results of the study will be shared as publications in peer-reviewed journals and at scientific meetings.  All data to
 be shared will be de-identified.  Study subjects may request to learn the results of the study, which will be provided
 orally by the study staff, or they will be referred to any publications.
When the Results Will Be Shared
At the end of the entire study, after IRB review and approval to share the final results.
Page 16 of 32


IRB-18-01336
Initial Application
Robert Ritch
14. Procedures - Compensation
Compensation for Participation
Yes
Type
Cash
Amount Per Visit
20
# of Visits
1
Line Total
20
Justification
Time
Who Will Pay
Specify Who Will Pay
Comment
Total Compensation
20
  
  PI must attest that all of the following are true. 
  * Credit for payment accrues as the study progresses. 
  * Payment is not contingent upon completing the entire study. 
  * The amount of payment and the proposed method and timing of disbursement is neither
 coercive nor presented undue influence. 
  * Any amount paid as a bonus for completion is reasonable and not so large as to unduly
 induce subjects to stay in the study when they would otherwise have withdrawn. 
  * All information concerning payment, including the amount and schedule of payments, is
 in the informed consent document. 
  * Compensation does not include a coupon good for a discount on the purchase price of
 the product once it has been approved. 
  
 
Page 17 of 32


IRB-18-01336
Initial Application
Robert Ritch
15. Consent - Obtaining Consent
Consent Process
Adult Consent
Where and When Consent Will Be Obtained
The study will be verbally explained to the potential subject by the participating physicians and study staff after their
 standard of care visit, who will provide all pertinent information (purpose, procedures, risks, benefits, alternatives
 to participation, etc.), and will allow the potential subject ample opportunity to ask questions.  Following this verbal
 explanation, the potential subject will be provided with a consent form and will be afforded sufficient time to consider
 whether or not to participate in the research. After allowing the potential subject time to read the consent form, the
 investigator or study staff will answer any additional questions the potential subject may have and will obtain verbal
 agreement and written agreement to participate in the research, by signing the informed consent form.  The entire
 informed consent process will take place in a private room at the study site, Suite 500 of the South Building of the
 New York Eye and Ear Infirmary,
Waiting Period for Obtaining Consent
The subject will be afforded sufficient time to consider whether or not to participate in the research. Sufficient time in
 this study should be minutes, which should be how long it would reasonably take to evaluate the procedures, risks,
 potential benefits, and potential alternatives.
SOP HRP-090 Informed Consent
 Process for Research Is Being
 Used
Yes
PPHS Worksheets, Checklists and SOPs
  
Process to Document Consent in
 Writing
Will Use Standard Template
Non-English Speaking Participants
 Will Be Enrolled
No
Justification for Not Enrolling Non-English Speaking Participants
This is a study to measure the NFC blood flow after NF application of LTB in 120 POAG patients compared to change
 in NFC blood flow after NF application. The study is powered to assess the hemodynamic effects for pre- vs. post-
nailfold application of LTB. We do not have resources to generate consents in different languages or to employ
 interpreters. There is no therapeutic benefit for study participation.
Page 18 of 32


IRB-18-01336
Initial Application
Robert Ritch
16. Consent - Documents
Consent Documents
Type
informed consent
Name
IDEATE CONSENT Nailfold
Upload
IDEATE CONSENT Nailfold.pdf
Consent Templates
  
Page 19 of 32


IRB-18-01336
Initial Application
Robert Ritch
17. Data - Collection
Health Related Information Will Be
 Viewed, Recorded, or Generated
Yes
Description of Health Information That Will Be Viewed, Recorded, or Generated
Health information that will be viewed, recorded or generated include:
baseline height, weight, blood pressure, pulse, and NF capillaroscopy, medical history including: age, sex, ancestry,
 body mass index, baseline blood pressure, baseline pulse, hypertension (yes/no), diabetes mellitus (yes/no), current
 smoker (yes/no), use of antiplatelet or anticoagulant, max known intraocular pressure, current intraocular pressure,
 current cup-disc ratio, current mean deviation and pattern standard deviation from worse eye from latest reliable
 Humphrey visual field test.
Non-Health Related Information Will
 Be Viewed or Recorded
No
HIV / AIDS Related Information Will
 Be Viewed or Recorded
No
Data That Will Be Viewed,
 Recorded, or Generated Contains
 ANY of the Following Directly
 Identifiable Information
Yes
Will Be Viewed
Name, Medical Record Number, Address
 by street location, Telephone number, Fax
 number, Geographical Subdivisions Smaller
 Than a State, All Elements of Dates for
 Dates Directly Related to an Individual (i.e.,
 Birth Date, Admission Date, Discharge
 Date)
Will Be Recorded
Name, Medical Record Number, Address
 by street location, Telephone number, Fax
 number, Geographical Subdivisions Smaller
 Than a State, All Elements of Dates for
 Dates Directly Related to an Individual (i.e.,
 Birth Date, Admission Date, Discharge
 Date)
Data Collection Sheet
        
        A Data Collection Sheet is required if you are either performing a retrospective review,
 or your study meets the category of exempt 4 research, or your study meets the category
 of expedited 5 research. Please upload it here.
        
    
Data Collection Source(s)
Participant, Medical Chart (Paper or
 Electronic)
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IRB-18-01336
Initial Application
Robert Ritch
18. Data - HIPAA
Obtaining HIPAA Authorization
Yes
How PHI Will Be Protected from Improper Use or Disclosure
PHI will be disclosed to the PI and NYEEIMS research staff associated to this project only.  Proper password
 protected computers and data analysis sheets requiring password authorization will be in place.
PHI Will Be Destroyed at the
 Earliest Opportunity Consistent
 with the Research
Yes
When and How PHI Will Be Destroyed 
PHI will be destroyed after data analysis and estimated 6 years after post publication of final results.  
PHI Will Be Shared
No
  PI must attest to the following.
  * I assure that the protected health information (PHI) will not be disclosed to any other
 person or entity not listed on this form except where required by law or for the authorized
 oversight of this research project. If at any time I want to reuse this PHI for other purposes
 or disclose it to other individuals or entities I will seek approval from the IRB. 
  
 
Page 21 of 32


IRB-18-01336
Initial Application
Robert Ritch
19. Data - Storage
Location Where Data Will Be Stored
The PI and principal Study coordinator for this trial will be holding the needed protected health information below in
 a research study staff access, password protected computer and hard copies in a locked cabinet at the NYEEIMS
 Clinical Research Center, 310 East 14th Street, Suite 500 South bldg.
How will the data be stored?
With a Code That Can Be Linked to the
 Identity of the Participant
Research Personnel Responsible
 for:
Robert Ritch
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Yes
Research Personnel Responsible
 for:
Ahmad Najafi
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Research Personnel Responsible
 for:
Erica B. Jacobs
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Research Personnel Responsible
 for:
Maria Scolaro
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Yes
Research Personnel Responsible
 for:
Elena Alvarado
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Research Personnel Responsible
 for:
Emily Seo
Accessing Data
Receipt or Transmission of Data
Holding Code That Can Be Linked
 to Identity of Participants
Research Personnel Responsible
 for:
Harriet Lloyd
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants


Research Personnel Responsible
 for:
Katy Tai
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Research Personnel Responsible
 for:
Louis Pasquale
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Yes
Research Personnel Responsible
 for:
Mark Gentile
Accessing Data
Receipt or Transmission of Data
Holding Code That Can Be Linked
 to Identity of Participants
Duration Data Will Be Stored
Study records will be maintained for approximately 6 years, for the purpose of analysis, published reports and
 followup. Although the study will consist of a single visit for each subject, the subjects will be asked for permission to
 be contacted at a
future date.
Steps That Will Be Taken to Secure the Data During Storage, Use, and Transmission
During the informed consent process, subjects will be informed of the precautions that will be taken to protect the
 confidentiality of the data and be informed of the parties who will or may have access (e.g., research team, FDA,
 OHRP). This will allow subjects to decide about the adequacy of the protections and the acceptability of the possible
 release of private information to the interested parties. 
Provisions for protecting privacy and/or confidentiality are relevant at all stages of research, including subject
 identification and recruitment, research participation, and analysis of individually identifiable data. 
To minimize potential risks, observations would be recorded whenever possible in a manner that does not allow
 participants to be identified, either directly or through identifiers linked to them. When identifiers are necessary for the
 research, adequate provisions for maintaining the confidentiality of the data are required.
Power Analysis/Data Analysis Plan (Including Any Statistical Procedures)
Chi squared and unpaired t-tests will be used for between group comparisons.  Paired t-tests will be used for pre- to
 post-NF drug application comparisons. Multivariable analysis will be performed to determine if NFC LTB application
 is an independent predictor of change in NFC blood flow from baseline to after drug application. 
Power calculations indicate that with our sample size of 120 we have 90% power to detect changes in blood flow
 difference between baseline and after NF application  in the latanoprost group versus normal saline group and  in
 the LTB group versus the normal saline controls.  We have 80% power to detect changes in blood flow difference
 between baseline and after NF application in the LTB group versus latanoprost group. These calculations are based
 on a 1:2:2 sampling ratio, a type 1 error rate of 5% and 30% variance in measurement of NFC blood flow.  We
 assume that because latanoprost itself will upregulate NO, that LTB will enhance NO donation by another 50%.
Page 23 of 32


IRB-18-01336
Initial Application
Robert Ritch
20. Data - Safety Monitoring
More Than the Minimum Data
 Safety Monitoring Will Be Done
No
  
  The following minimum requirements apply to all projects, including retrospective
 reviews of medical records, use of tissue samples, and many minimal risk studies, such
 as observational and survey research. Because these minimum requirements apply to
 all studies, a specific written DSMP will not usually be required for projects that do not
 pose greater than minimal risk to subjects. The MSSM PPHS may alter the required level of
 monitoring if appropriate. 
  For all projects, the principal investigator must have a plan to assure that data integrity
 will be maintained during its collection, storage and analysis. All research projects
 must adhere to MSSM recommendations on the storage of research data. Loss of data
 containing identifiable information is reportable to the IRB within 5 business days.
  Any problems concerning the consent process and any subject complaints should be
 monitored by the investigator. Reports of such problems must be made at least annually.
 The discretion of the protocol director will guide the need to report these problems
 immediately or more frequently.
  The principal investigator is, typically, the monitoring entity for the minimum DSMP. When
 a principal investigator is not a faculty member, the supervising faculty member must be
 responsible for the data and safety monitoring aspect of the protocol.
     
 
Will the Research Include Data
 Coordinating Center Activities?
No
Page 24 of 32


IRB-18-01336
Initial Application
Robert Ritch
21. Funding
Funding Source Name
Bausch And Lomb
Contact
Funding Category
Other
Meditrack (https://contracts.tractmanager.com/Contracts/Login.aspx)
Grant or Contract Title
Effect of Nailfold Application of Latanoprostene Bunod on Nailfold Capullary Blood Flow;
 Grant ID 17291
Grant or Contract 
 Number
18-2686-00001-01
Funding Status
Funded
Project Initiated By
Investigator
Grant / Contract Principal
 Investigator (PI)
Robert Ritch
Department
Ophthalmology
Department
Ophthalmology
Phone
2126735140
Email
rritch@nyee.edu
Protocol and Funding
 Proposal Match
Yes
Identify Substantive
 Differences Between
 Protocol and Funding
 Proposal
Page 25 of 32


IRB-18-01336
Initial Application
Robert Ritch
22. Drugs / Biologics
Study Fund Account (or
 alternate departmental /
 fund account, if study is
 not yet established)
02444850
Generic Name
Latanoprost 0.005%
Brand Name
Xalatan
Drug Has Valid IND
No
For each drug / biologic with an IND number, ensure that the application includes one
 of the following. * Sponsor protocol with the IND number. * Communication from the
 sponsor or the FDA with the IND number.
IND Number
Name of IND Holder
Type of IND Holder
Drug Meets One of the
 Following Categories for
 Exemption
Yes
Category 1: * The drug is lawfully marketed in the United States. * The research is
 not intended to be reported to the FDA as a well-controlled study in support of a new
 indication for use nor intended to be used to support any other significant change
 in the labeling for the drug. * The research is not intended to support a significant
 change in the advertising for the product. * The research does not involve a route
 of administration or dosage level or use in a patient population or other factor that
 significantly increases the risks (or decreases the acceptability of the risks) associated
 with the use of the drug. * The research is conducted in compliance with the marketing
 limitations described in 21 CFR §312.7. Category 2: * A clinical investigation for an
 in vitro diagnostic biological product that involves one or more of the following: (1)
 Blood grouping serum; (2) Reagent red blood cells; or (3) Anti-human globulin. * The
 diagnostic test is intended to be used in a diagnostic procedure that confirms the
 diagnosis made by another, medically established, diagnostic product or procedure.
 * The diagnostic test is shipped in compliance with 21 CFR §312.160. Category 3:
 * A clinical investigation involving use of a placebo when the investigation does not
 otherwise require submission of an IND.
Category for Exemption
Category 1
Justification for Meeting
 Criteria
Latanoprost 0.005% meets all of the criteria in Category 1.
To be a coordinating center, the Mount Sinai investigator is the Principal Investigator for
 multi-site participation in the trial. The Investigational Drug Service (IDS) may support
 trials as the coordinating center. IDS services include but are not limited to randomizing
 for other sites, storing and shipping drugs to participating sites, etc.
Icahn School of Medicine
 at Mount Sinai (ISMMS)
 Is the Coordinating
 Center
Role of the
 Investigational Drug
 Service (IDS)
Drug / Biologic
 Description
 (Manufacturer/Generic
 Name/Form/Strength)
Controlled Substance
Schedule
In order for the Icahn School of Medicine at Mount Sinai (ISMMS) to be compliant with
 the regulations regarding controlled substance research, a New York State Department


 of Health-issued Researcher license and DEA-issued Researcher Registration Number
 must be on file for each trial using controlled substances. The Investigational Drug
 Service maintains these licences and will make them available to our investigators to
 support our research. Refer to www.health.state.ny.us/professionals/narcotic and http://
firstclinical.com/journal/2011/1112_DEA.pdf for more information.
Using Investigational
 Drug Service (IDS)
 Research License
Use of this Drug /
 Biologic Is Considered
 Standard of Care
Requested Pharmacy
 Services
Specify Other Requested
 Pharmacy Services
Drug / Biologic Will Be
 Supplied By
Specify Other Drug /
 Biologic Supplier
Using Placebo
Placebo Will Be Supplied
 By
Compounding Required
 (Paid for by Study
 Funds)
Where Drug / Biologic
 Will Be Administered
Specify Location of
 Private Office
Storage Requirements of
 Drug / Biologic
Where Drug / Biologic
 Will Be Stored
ALL of the Following
 Storage Criteria Are Met
* The storage area is well maintained, provides adequate lighting, ventilation, sanitation,
 space and security. * The temperature in the storage area is controlled and monitored
 using calibrated monitoring devices. * The temperature monitoring system has sensors
 for continuous monitoring and alarms set at the points representing the temperature
 extremes. * Records of temperatures and alarms are maintained and all excursions
 outside the labeled storage conditions are appropriately investigated and reported to
 the sponsor.
Justification Why Any
 of the Above Storage
 Criteria Cannot Be Met
ALL of the Following
 Distribution Criteria Are
 Met
* The investigator will not dispense the investigational agent to any person not
 authorized under the protocol to receive it. * The drug, agent, biologic may only be
 used in subjects under the investigators personal supervision or under the supervision
 of a physician who is directly responsible to the investigator. * The investigator will
 maintain adequate records for the receipt, storage, and disposition of the drug,
 including dates, quantity, and use by subjects. * The investigational agents will be
 stored in a secure area and in such a way to restrict access to authorized personnel
 only as defined in the protocol. Additionally, all associated records will be stored in a
 restricted area and/or locked.


Justification Why Any of
 the Above Distribution
 Criteria Cannot Be Met
Generic Name
Latanoprostene bunod 0.024%
Brand Name
Vyzulta
Drug Has Valid IND
No
For each drug / biologic with an IND number, ensure that the application includes one
 of the following. * Sponsor protocol with the IND number. * Communication from the
 sponsor or the FDA with the IND number.
IND Number
Name of IND Holder
Type of IND Holder
Drug Meets One of the
 Following Categories for
 Exemption
Yes
Category 1: * The drug is lawfully marketed in the United States. * The research is
 not intended to be reported to the FDA as a well-controlled study in support of a new
 indication for use nor intended to be used to support any other significant change
 in the labeling for the drug. * The research is not intended to support a significant
 change in the advertising for the product. * The research does not involve a route
 of administration or dosage level or use in a patient population or other factor that
 significantly increases the risks (or decreases the acceptability of the risks) associated
 with the use of the drug. * The research is conducted in compliance with the marketing
 limitations described in 21 CFR §312.7. Category 2: * A clinical investigation for an
 in vitro diagnostic biological product that involves one or more of the following: (1)
 Blood grouping serum; (2) Reagent red blood cells; or (3) Anti-human globulin. * The
 diagnostic test is intended to be used in a diagnostic procedure that confirms the
 diagnosis made by another, medically established, diagnostic product or procedure.
 * The diagnostic test is shipped in compliance with 21 CFR §312.160. Category 3:
 * A clinical investigation involving use of a placebo when the investigation does not
 otherwise require submission of an IND.
Category for Exemption
Category 1
Justification for Meeting
 Criteria
Latanoprostene bunod 0.024% meets all criteria listed for category 1.
To be a coordinating center, the Mount Sinai investigator is the Principal Investigator for
 multi-site participation in the trial. The Investigational Drug Service (IDS) may support
 trials as the coordinating center. IDS services include but are not limited to randomizing
 for other sites, storing and shipping drugs to participating sites, etc.
Icahn School of Medicine
 at Mount Sinai (ISMMS)
 Is the Coordinating
 Center
Role of the
 Investigational Drug
 Service (IDS)
Drug / Biologic
 Description
 (Manufacturer/Generic
 Name/Form/Strength)
Controlled Substance
Schedule
In order for the Icahn School of Medicine at Mount Sinai (ISMMS) to be compliant with
 the regulations regarding controlled substance research, a New York State Department
 of Health-issued Researcher license and DEA-issued Researcher Registration Number
 must be on file for each trial using controlled substances. The Investigational Drug
 Service maintains these licences and will make them available to our investigators to


 support our research. Refer to www.health.state.ny.us/professionals/narcotic and http://
firstclinical.com/journal/2011/1112_DEA.pdf for more information.
Using Investigational
 Drug Service (IDS)
 Research License
Use of this Drug /
 Biologic Is Considered
 Standard of Care
Requested Pharmacy
 Services
Specify Other Requested
 Pharmacy Services
Drug / Biologic Will Be
 Supplied By
Specify Other Drug /
 Biologic Supplier
Using Placebo
Placebo Will Be Supplied
 By
Compounding Required
 (Paid for by Study
 Funds)
Where Drug / Biologic
 Will Be Administered
Specify Location of
 Private Office
Storage Requirements of
 Drug / Biologic
Where Drug / Biologic
 Will Be Stored
ALL of the Following
 Storage Criteria Are Met
* The storage area is well maintained, provides adequate lighting, ventilation, sanitation,
 space and security. * The temperature in the storage area is controlled and monitored
 using calibrated monitoring devices. * The temperature monitoring system has sensors
 for continuous monitoring and alarms set at the points representing the temperature
 extremes. * Records of temperatures and alarms are maintained and all excursions
 outside the labeled storage conditions are appropriately investigated and reported to
 the sponsor.
Justification Why Any
 of the Above Storage
 Criteria Cannot Be Met
ALL of the Following
 Distribution Criteria Are
 Met
* The investigator will not dispense the investigational agent to any person not
 authorized under the protocol to receive it. * The drug, agent, biologic may only be
 used in subjects under the investigators personal supervision or under the supervision
 of a physician who is directly responsible to the investigator. * The investigator will
 maintain adequate records for the receipt, storage, and disposition of the drug,
 including dates, quantity, and use by subjects. * The investigational agents will be
 stored in a secure area and in such a way to restrict access to authorized personnel
 only as defined in the protocol. Additionally, all associated records will be stored in a
 restricted area and/or locked.
Justification Why Any of
 the Above Distribution
 Criteria Cannot Be Met


Page 30 of 32


IRB-18-01336
Initial Application
Robert Ritch
23. Financial Administration
  This information will help the Financial Administration of Clinical Trials Services (FACTS)
 office determine whether a Medicare Coverage Analysis (MCA) is needed for the research
 study. If you have any questions while completing this form, please contact the FACTS
 office at (212) 731-7067 or FACTS@mssm.edu.
  
 
Clinical Research Study Category
Investigator Initiated
  Payment Options: 
  * Option 1:  No protocol-required services will be billed to patients or third-party payers.
 Does Not Need MCA 
  * Option 2:  Protocol-required services (i.e., routine care services) will be billed to patients
 or third-party payers. Must Have MCA 
  * Option 3:  Study is initiated and federally funded by a Government Sponsored
 Cooperative Group who will only pay for services that are solely conducted for research
 purposes and other protocol-required services (i.e., routine care services) will be billed to
 patients or third-party payers. Billing Grid Only Required, NO MCA 
  * Option 4:  Study involves only data collection and has no protocol-required clinical
 services. Does Not Need MCA 
  * Option 5:  Study is not described in any of the above options. Please describe the study
 and specify whether External Sponsor (i.e., industry, government, or philanthropic source)
 and/or patient/third party payer will pay for protocol required services. MCA MAY Be
 Required 
  
 
Payment Option
Option 5
  
  MCA may be need to be prepared per option selected above. 
  
 
  
  Payment Option 5:   
  Please describe the study and specify whether External Sponsor (i.e., industry,
 government, or philanthropic source) and/or patient/third party payer will pay for protocol
 required services. 
  
 
Payment Option 5
Protocol-required eye exam procedures are being done as part of the patients routine clinical care and are billable to
 the patient or their insurance. The nailfold video capillaroscopy procedure is not approved for insurance billing and
 will not be charged to patients.
Page 31 of 32


IRB-18-01336
Initial Application
Robert Ritch
24. Attachments
Type
Name
Version Status
Filename
Uploaded
 Date
Funding Proposal /
 Grant Application
IRG Icahn School
 of Med ID 17291
 041318 LOA.pdf
1
approvedIRG Icahan School
 of Med ID 17291
 041318 LOA.pdf
11/23/2018
Contractual Scope of
 Work
IRG Icahn School
 of Med ID 17291
 041318 LOA.pdf
1
approvedIRG Icahan School
 of Med ID 17291
 041318 LOA.pdf
11/23/2018
Package Insert
 Document (DRUG
 NAME)
Xalatan Package
 Insert.pdf
1
approvedXalatan Package
 Insert.pdf
11/23/2018
Package Insert
 Document (DRUG
 NAME)
vyzulta-prescribing-
information.pdf
1
approvedvyzulta-prescribing-
information.pdf
11/23/2018
Approval Document
IRB-18-01336
 approval letter.pdf
1
approvedIRB-18-01336
 approval letter.pdf
09/23/2019
Consent - Consent
 Document
18-01336 ICF
 CLEAN version
 10-31-19
2
Deactivated
//
Consent - Consent
 Document
18-01336 ICF
 TRACKED version
 10-31-19
2
Deactivated
//
Consent - Consent
 Document
18-01336 ICF
 Revised Common
 Rule v4 CLEAN.docx
1
approved18-01336 ICF
 Revised Common
 Rule v5 CLEAN.docx
02/15/2019
Consent - Consent
 Document
18-01336
 ICF Revised
 Common Rule v4
 MARKED.docx
1
approved18-01336
 ICF Revised
 Common Rule v5
 MARKED.docx
02/15/2019
COI - Conflict of
 Interest Committee
 Management Plan
COI Management
 Plan- Dr. Pasquale
1
approvedManagement Plan
 - IF 2371320 -
 Effect of Nailfold
 Application of
 Latanoprostene
 Bunod on Nailfold
 Capillary Blood
 Flow.pdf
12/18/2019
 
Page 32 of 32