Prospective Controlled Study of Intranasal Tear Neurostimulation for Sjogrens Patients With Dry Eye Disease
Phase: NA
Conditions: Dry Eye Syndromes, Sjogren's Syndrome
Sponsor: University of Pennsylvania

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September 10, 2019 
 
US Department of Health and Human Services 
200 Independence Ave SW 
Washington, DC 20201 
 
PRINCIPAL 
INVESTIGATOR  
:  
Giacomina Massaro-Giordano  
TITLE  
:  
TrueTear in Sjogren’s Disease 
Patients  
PROTOCOL #  
:  
830076  
 
The following document spells out the study protocol and statistical analysis plan for 
this trial.  
 
   
  
 
Sincerely, 
 
 
Jonathan Lilley 
Research Coordinator  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol  
 
In this trial, the protocol is straightforward. The study consists of two visit days for the 
patient. The first day is considered the screening day. On the first day, a baseline 
Schirmer’s test is performed after the patient’s eyes have been anesthetized. The 
duration of this test is five minutes. At the end of the five minutes, the tear production 
is measured using the Schirmer strips. The patient must produce ten millimeters or less 
in at least one eye to qualify for the study. Next, the TrueTear device is simulated using 
two cotton swabs. One cotton swab is inserted into each nostril. Using Schirmer strips to 
measure tear production, the patient swirls the cotton swabs around in their nostrils 
until they produce four millimeters above their baseline in at least one eye. The patient 
is then to hold the cotton swabs in their nose for the remainder of the five minutes. In 
order to qualify for the study, the patient must produce four millimeters or greater in 
the study eye. In instances where the patient is of child-bearing age, a pregnancy test is 
performed to ensure that the patient is not pregnant.     
 
After visit one, visit two can be completed the following day or any day during the next 
forty-five days. During visit two, the effectiveness of the device is tested. The patient is 
randomized to which application method, internal or external, is used first. During both 
the first and second applications, Schirmer strips are used to measure tear production 
over the course of five minutes. For the first three minutes, the device is used. For the 
remaining two minutes, the device is removed. Between the first and second 
applications, there must be a waiting period of at least forty-five minutes. This break 
ensures that the patient’s tear glands have enough time to restore. This is necessary for 
accurate measurement of the effectiveness of the device.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Statistical Analysis Plan 
 
Our plan to analyze the data from this trial will involve a few different comparisons, as 
well as factoring in a few different variables. First, we will look to compare both the 
internal and external stimulation results to the baseline results. When making these 
comparisons, the order in which application method was used first will be factored in. 
This will help us determine whether or not the order of application methods impacts the 
final results. Next, we will examine each stimulation method (cotton swabs, internal 
application with TrueTear device, and external application with TrueTear device) relative 
to baseline to see if the changes are statistically significant from baseline, and to 
determine an estimated mean change. We also plan to compare each application method 
to each other to determine if there is a statistically significant difference. While making 
the comparison, we also want to separately account for two different factors, patients on 
Sjogren’s medication vs. patients not on Sjogren’s medication and patients with a 
baseline Schirmer of less than 5 mm. vs. patients with a baseline Schirmer of greater than 
or equal to 5 mm. In a similar fashion, we also want to examine each application method 
individually to determine the p-value, confidence interval, mean, and standard deviation.