We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613001075774
Ethics application status
Approved
Date submitted
28/08/2013
Date registered
25/09/2013
Date last updated
25/08/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Stimulation Therapy to Produce Tears for the Treatment of Dry Eye
Scientific title
Neurostimulation to Increase Tear Production Measured Objectively via Schirmer Test in Adult Patients with Mild to Severe Dry Eye Disease - Pilot Study
Secondary ID [1] 283096 0
Nil known
Universal Trial Number (UTN)
U1111-1146-7736
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry eye disease 289933 0
Condition category
Condition code
Eye 290308 290308 0 0
Diseases / disorders of the eye
Eye 290309 290309 0 0
Normal eye development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - Neurostimulation device (EMS 2000) - Lacrimal gland neurostimulation. The current provided is approximately 1 milliamp with the patient controlling the amplitude with a knob. The recommended duration of treatment is approximately 30 seconds and the recommended treatment frequency is four times per day or as needed. The duration of the intervention period is 6 months.

Patient diaries are used to monitor adherence to the intervention.
Intervention code [1] 287814 0
Treatment: Devices
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290345 0
Mean Schirmer test score compared to baseline
Timepoint [1] 290345 0
At 6 months after start of study treatment
Primary outcome [2] 290346 0
Adverse events - Possible adverse events can include headache, pain/discomfort, and nosebleed, all assessed through case history.
Timepoint [2] 290346 0
At 6 months after start of study treatment
Secondary outcome [1] 304333 0
Mean Ocular Surface Disease Index score compared to baseline
Timepoint [1] 304333 0
At 6 months after start of study treatment
Secondary outcome [2] 304334 0
Mean dry eye symptoms as assessed by a Visual Analogue Scale compared to baseline
Timepoint [2] 304334 0
At 6 months after start of study treatment

Eligibility
Key inclusion criteria
Willing to sign the informed consent and deemed capable of following the study protocol

Basal Schirmer tear test of less than or equal to 15 mm; Schirmer test at least twice or at least 10 mm higher after nasal stimulation with cotton swab

Baseline Ocular Surface Disease Index score of at least 13

Normal lid anatomy, blinking function and closure

Corrected visual acuity of 20/200 (Snellen equivalent) or better in each eye
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Individuals with a history or presence of any systemic disorder or condition that is not stabilized or would likely interfere with the interpretation of study results or subject safety

Presence of severe systemic allergy or acute or chronic rhinitis or sinusitis

Individuals with the presence or history of any ocular disorder or condition that would likely interfere with the interpretation of study results or subject safety

Nasal, orbital or lacrimal trauma, surgery, tumour or cancer

Significant corneal or conjunctival scarring of any aetiology

Known hypersensitivity to one of the components of the study device or procedural medications

Patients with a history of chronic or recurrent epistaxis

Participation in any clinical trial with a new active substance or a new device during the past 3 months

Women who are pregnant, planning a pregnancy or nursing at study entry

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Prospective
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A statistical comparison of treatment to baseline data will be analyzed. Data will be tested for normality. Data will be analyzed using descriptive statistics and/or using typical statistical analyses for normally distributed data sets (e.g. ANOVA, Tukey’s multiple comparison test, Student’s t-test, etc.). Appropriate transformations or tests will be utilized for non-normally distributed data. Additional statistical tests (e.g. binomial probability tests, etc.) may be used as needed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5342 0
Mexico
State/province [1] 5342 0
Baja California

Funding & Sponsors
Funding source category [1] 287848 0
Commercial sector/Industry
Name [1] 287848 0
Oculeve, Inc.
Address [1] 287848 0
395 Oyster Point Blvd.
Suite 501
South San Francisco, California 94080 USA
Country [1] 287848 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Oculeve, Inc.
Address
395 Oyster Point Blvd.
Suite 501
South San Francisco, CA 94080 USA
Country
United States of America
Secondary sponsor category [1] 286578 0
None
Name [1] 286578 0
Address [1] 286578 0
Country [1] 286578 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289790 0
CODET Vision Institute Comite de Investigacion y Etica
Ethics committee address [1] 289790 0
Ave Padre Kino 10159
Zona Rio, Tijuana, B.C. C.P. 22320
Ethics committee country [1] 289790 0
Mexico
Date submitted for ethics approval [1] 289790 0
01/05/2013
Approval date [1] 289790 0
10/05/2013
Ethics approval number [1] 289790 0
SSA Junio 09, 2009

Summary
Brief summary
The purpose of this study is to demonstrate that neurostimulation increases tear production and improves symptoms of dry eye disease over baseline measurements.
Trial website
Trial related presentations / publications
Friedman NJ, Butron K, Robledo N, Loudin J, Baba SN, Chayet A. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease. Clin Ophthalmol 2016;10:795-804.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862385/
Public notes

Contacts
Principal investigator
Name 42458 0
Dr Arturo Chayet, MD
Address 42458 0
CODET Vision Institute
Av Padre Kino No. 10159
Zona Rio, Tijuana, BC 22320
Country 42458 0
Mexico
Phone 42458 0
+52 664 9792020
Fax 42458 0
+52 664 6824096
Email 42458 0
martha.federico@codetvision.com
Contact person for public queries
Name 42459 0
Mr Daniel Hamilton
Address 42459 0
Oculeve Inc.
395 Oyster Point Boulevard
Suite 501
South San Francisco, CA 94080, USA
Country 42459 0
United States of America
Phone 42459 0
1 415 5806236
Fax 42459 0
+1 650 7370200
Email 42459 0
dan@oculeve.com
Contact person for scientific queries
Name 42460 0
Dr Arturo Chayet, MD
Address 42460 0
CODET Vision Institute
Av Padre Kino No. 10159
Zona Rio, Tijuana, BC 22320
Country 42460 0
Mexico
Phone 42460 0
+52 664 9792020
Fax 42460 0
+52 664 6824096
Email 42460 0
martha.federico@codetvision.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary