Clinical trial NCT03615508
Conditions: Horner Syndrome
Keywords: Alpha blockers Tamsulosin
Sponsor: Denver Health and Hospital Authority
Start date: 2018-09-21; Completion date: 2019-05-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is evaluating the pupil dilation of Horner's Patients who have ever taken an alpha blocker such as Tamsulosin. Patients will undergo eye dilation as would occur at a yearly eye examination, but their pupil dilation measurements will be recorded.

Detailed description:
This study will enroll 10 participants who have a unilateral Horner's Syndrome AND have a history of taking an alpha blocker such as Tamsulosin. Participants will be recruited based on those two enrollment criteria, and after consenting they will undergo pupil dilation with 10% phenylephrine. Once fully dilated the pupil size will be measured. Pupil dilation size of the eye affected by the Horner's Syndrome will be compared to the eye not affected by Horner's. Primary study outcome is the comparative dilation size of the Horner's affected eye to the non affected eye in all subjects.

Arms: arm 1: All patients will receive 10% phenylephrine at their eye examination as the drug to dilate the pupil. After pupil dilation, pupil size will be measured.
Interventions: intervention 1: 10% phenylephrine
Intervention descriptions: intervention 1: 10% phenylephrine is a drug that can be used to dilate patient's eyes at their yearly eye examination. All enrolled subjects will receive this drug for their eye dilation.

Protocol documents:
Prot_SAP_000.pdf: 
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Exploration of Pupil Dilation in 
Horner's Patients Taking Flomax 
 
 
 
NCT03615508 
 
 
 
July 17th, 2020


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COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490    TELEPHONE:  303-724-1055  Fax:  303-724-0990 
 
 
 
Protocol #: 18-0620 
Project Title: 
Exploration of Pupil Dilation in Horner's Patients Taking Flomax 
 
 
 
Principal Investigator:  Cristos Ifantides, MD, MBA 
Version Date: 7/12/2018 
 
 
 
 
  
 
I. Hypotheses and Specific Aims:  
Hypothesis:  In patients who suffer from Horner’s Syndrome and have used an alpha blocker at any 
time in the past, use of topical ophthalmic eye drops phenylephrine 10% will dilate the Horner’s 
Syndrome affected eye more compared to the unaffected eye.   
 
Primary Aim:  To determine the average increased dilation size in the effected Horner’s eye 
compared to the unaffected eye.  
 
Secondary Aim:  To provide proof-of-concept data for future studies validating that in patients who 
take tamsulosin (Flomax) or another less common alpha blocker and suffer from Floppy Iris 
Syndrome, inducing a temporary “pharmacologic Horner’s Syndrome” can serve as treatment by 
increasing the effective pupil dilation of these patients.  
 
 
 
IV. Research Methods 
 
A.  Outcome Measure(s):   
The primary hypothesis for this study is that Phenylephrine Hydrochloride Ophthalmic Solution 
10% will dilate the affected Horner’s eye more than the non affected eye in patients previously 
treated with an alpha  blocker).  
 
The primary outcome measure for this single arm study is pupil diameter size status post 
phenylephrine 10% of the Horner’s eye compared to the non-Horner’s eye.  
 
The secondary outcome is the change in pupil diameter of each eye post-intervention compared 
to pre-intervention dilating drops.   The average change in pupil size between Horner’s eye 
compared to the non-Horner’s eye will be determined.   
 
B. Description of Population to be Enrolled:   
This study will recruit all adult patients seen at Denver Health or University of Colorado 
Hospital with a diagnosis of Horner’s Syndrome who have any history of taking tamsulosin 
(Flomax).   Adult patients must be able to consent for study participation by themselves.  
Exclusion criteria that will eliminate potential subjects for enrollment includes: 
1) Subjects with untreated hypertension 
2) Subjects with thyrotoxicosis 
3) Pregnant women 
4) Prisoners 
5) Inability to consent 
6) Subjects with anatomical narrow angles who have never had a dilated exam 
 
 


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C. Study Design and Research Methods   
This is a single arm study investigating the difference in pupil dilation in Horner’s Syndrome 
patients with a history of taking tan alpha blocker.   Patients with a history of tamsulosin/ 
terazosin/doxazosin/alfuzosin/silodosin medication, even for short durations are at high risk 
for developing Floppy Iris Syndrome.  This study will test the hypothesis that patients with 
Floppy Iris Syndrome have greater pupil dilation in the affected Horner’s eye compared to 
the non-affected eye.   
 
Through medical record chart review we will identify patients with a diagnosis of Horner’s 
Syndrome and a history of taking Flomax.  We anticipate some of these patients will be 
patients within the Denver Health Eye Clinic or the Rocky Mountain Lions Eye Institute 
whom the investigator has a clinical relationship.   We anticipate some potential subjects 
will not be patients either of these clinics.  These potential subjects will be contacted for 
participation, as well.  If necessary, we will recruit using COMPASS if enrollment numbers 
from these two institutions are lower than expected.  
 
Potential subjects will be contacted in one of two ways: 1) potential subjects who are eye 
clinic from one of the two centers patients will be approached in the Eye Clinic by a study 
member who has been notified by the clinic staff.  2) Potential subjects who are not current 
patients at these clinics will be contacted through the phone number in their medical 
record.  These patients will be called a maximum of two times to inform them of potential 
study participation.   HIPAA Waiver will be used to contact these potential subjects.  In the 
initial phone call with these subjects, history of tamsulosin or similar alpha antagonist will 
be confirmed over the phone so as to prevent an unnecessary visit.   
 
Once contacted, subjects will be informed of the study and the inclusion criteria will be 
reviewed with the subject.  If contact occurs in person at the eye clinics, the consent will 
occur at that time and study procedures will occur at that eye exam appointment.   If 
contact initially occurs over the phone, the patient will be invited in to the the clinic for face-
to-face consent process and pupil dilation.  They will be informed that this pupil dilation can 
occur as part of a yearly, standard eye examination if they are in need of one, but if they do 
not need an eye examination for the year, we will only dilate their eyes and measure pupil 
diameter, and limit the exam to only the anterior part of the eye.      
 
For all patients, consent will occur in person in the eye clinics in a private setting.  Consent 
will be obtained by a member of the research team.  Once consent has occurred, the 
principal investigator (PI) or another member of the study team will examine the patient’s 
anterior eye segment and measure the subject’s pupil diameter prior to instilling dilating 
drops.   Pupil measurements will occur with the use of a Digital Pupilometer (NeuroOptics 
Inc, Irvine, California, USA)  The Digital Pupillometer measures objective pupil size and 
reactivity data independent of the examiner and allows changes in pupil reactivity to be 
trended over time.   
 
After measurement of both pupils in a photopic light setting in the clinical examination 
room, 10% phenylephrine drops will be placed on the subject’s eyes by the PI.    
Measurement post dilation will occur 30 minutes after instillation of phenylephrine.   After 
the pupil measurement with the pupillometer, the study related activity will be complete.  If 
patients are in the clinic for their regular examination, the clinic specialists will commence 
the exam at that time.  
 
All subjects will be paid for their participation in this study.  A ClinCard with $25 will be 
distributed to each subject as reimbursement for their time and travel.   
 
The pupil measurements will be stored in a private, password protected Excel database for 
this study.  This database will contain patient’s name, MRN, age, sex, past medical history, 


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and current medications, along with the pupil measurements.  The PHI from this database 
will be deleted after the study concludes, but the pupillometer readings will remain paired 
with de-identified medical data.  Denver Health will serve as the coordinating site of data 
between the two sites; no PHI will be shared among the two sites.  
 
D. Description, Risks and Justification of Procedures and Data Collection Tools: 
This study will administer the standard dose of Phenylephrine Hydrochloride Ophthalmic 
Solution 10% (Akorn Inc, Lake Forrest, IL, USA)  This solution is an α-1 adrenergic 
receptor agonist that is FDA approved for the indication of pupil dilation.  We will be using 
this drug for the specific FDA approved indication and will use the standard accepted 
dosage.  All patients will receive one drop of Phenylephrine Hydrochloride Ophthalmic 
Solution 10% strength to the conjunctival fornix.  
 
Phenylephrine Hydrochloride Ophthalmic Solution 10% has a well known and accepted 
side effect profile.  Some common side effects that patients may experience during the 
clinic eye examination, or as part of this study if not participating in a yearly eye 
examination, include eye pain and stinging upon instillation, temporary blurred vision and 
photophobia, and conjunctival sensitization during examination.  Cardiovascular adverse 
reactions are rare but have been reported in hypertensive patients include an increase in 
blood pressure, syncope, myocardial infarction, tachycardia, arrhythmia and subarachnoid 
hemorrhage.  For this reason, Phenylephrine Hydrochloride Ophthalmic Solution 10% is 
contraindicated in hypertensive patients.  Phenylephrine Hydrochloride Ophthalmic 
Solution 10% is contraindicated in patients with a diagnosis of thyrotoxicosis as well.  We 
will exclude these two patients from participation in the study.   
 
Patient names and MRNs will be recorded in the database for the duration of this study.  
This database will be stored on the secure servers at each site under restricted access and 
password protected.  There is a small risk for breach of confidentiality when storing PHI for 
research.  The research team will do everything to ensure confidentiality of the subjects.  
At the completion of the study the names and MRNs will be deleted from the database and 
the remaining information (pupil diameters and medical history) will be unidentifiable.   
 
The potential benefit of this study is to society and future ophthalmic surgical patients with 
a history of taking Flomax or another alpha blocker.  
 
 
F.   Data Analysis Plan:   
This is a small pilot study exploring the potential pupil dilation change in eyes with an 
upregulated number of α receptors compared to normal irises.  This study is not powered 
to determine the clinically significant change that occurs with pupil dilation after topical 
placement of Phenylephrine Hydrochloride 10% strength.  Continuous variables will be 
analyzed using a linear regression model of covariates.   Categorical predictor variables 
will be analyzed using chi square test.  
 
 H. References: 
1. Chang, D.F. and Campbell, J.R., 2005. Intraoperative floppy iris syndrome associated with 
tamsulosin. Journal of Cataract & Refractive Surgery, 31(4), pp.664-673. 
2. Flach AJ. Intraoperative floppy iris syndrome: pathophysiology, prevention, and treatment. 
Transactions of the American Ophthalmological Society. 2009 Dec;107:234. 
3. Chang, D.F., Osher, R.H., Wang, L. and Koch, D.D., 2007. Prospective multicenter 
evaluation of cataract surgery in patients taking tamsulosin 
(Flomax). Ophthalmology, 114(5), pp.957-964. 
4. Theodossiadis PG, Achtsidis V, Theodoropoulou S, Tentolouris N, Komninos 
C, FountasKN. The effect of alpha antagonists on pupil dynamics: implications for the 
diagnosis of intraoperative floppy iris syndrome. American journal of ophthalmology, 
153(4), pp.620-622 


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