Intra-Nasal Mechanical Stimulation (INMEST) as a Treatment Method for the Relief of Symptoms of Dry Eye

Study Overview
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Brief Summary
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The purpose of the study is to investigate the degree of symptom relief in people with signs or symptoms of dry eyes after self-treatment at home with the Walther System delivering INMEST (intranasal mechanical stimulation). A total of 110 subjects are planned to be enrolled and randomized to either use an active device or a sham device. Both groups will also receive standard treatment in mainstream healthcare for symptoms of dry eye. The subject self-administer treatments at home, three times a week for six weeks, with a follow-up period of three months after end of treatment.

Official Title
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Intra-Nasal Mechanical Stimulation (INMEST) as a Treatment Method for the Relief of Symptoms of Dry Eye - A Prospective, Double-blind, Pivotal Study to Evaluate the Safety and Performance of the Walther System

Conditions
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Dry Eye, Dry Eye Syndromes

Intervention / Treatment
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* Device: Walther System
* Device: Sham Walther System
* Drug: Non preserved ocular lubricants
* Procedure: Eye lid procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 The study subject reports having understood and signed the Informed Consent Form (ICF) and is willing to comply with all investigation visits and assessments History of dry eye in both or one eye, supported by a previous clinical diagnosis or have self-reported history of complaints for at least 4 months prior to enrolment Women of childbearing potential must agree to use a reliable, medically approved form of contraception during the study participation until end of study OSDI score > 15 Non-Invasive tear Break-Up Time (NIBUT) ≤ 10 seconds Anticipated compliance with prescribed treatment and follow-up Exclusion Criteria: Recently (3 months prior enrolment) undergone nasal or sinus surgery Women who are pregnant as determined by urine test at inclusion and prior to study start (applies to sites in Denmark only) Ongoing acute upper respiratory tract infection, per the Investigator's judgement Bleph-ex treated within 3 months prior to enrolment The study subject has a cognitive incapacity or language barrier precluding adequate understanding or cooperation The study subject is considered by the Investigator to be unsuitable to participate in the investigation for any other reason Any severe diseases interfering with the performance, evaluation, and outcome of the clinical evaluation Previous (within 30 days prior to enrolment/randomization) and concurrent treatment during the treatment phase with another investigational drug/s or device/s

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pivotal, double-blind, randomized, multicentre study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Investigational device treament and standard treatment<br>After an initial demonstration of the device, study subjects will be given the device to be used for self-administration at home, 10 minutes per day in each nasal cavity, 3 days a week, for a total treatment period of six weeks. | Device: Walther System<br>* Walther System providing INMEST treatment<br>Drug: Non preserved ocular lubricants<br>* Hyaluronic acid (HyloGel) Hyaluronic acid and Ectoin (Hylo Dual Intense) Hyaluronic acid and Trehalos (Theloz Duo)<br>Procedure: Eye lid procedure<br>* Lid hygiene, warm eye bag, lid massage and Omega 3<br>|
| Sham Comparator: Sham device treatment and standard treatment<br>After an initial demonstration of the device, study subjects will be given the device to be used for self-administration at home, 10 minutes per day in each nasal cavity, 3 days a week, for a total treatment period of six weeks. | Device: Sham Walther System<br>* Walther System not providing INMEST treatment, but otherwise behave as the active comparator.<br>Drug: Non preserved ocular lubricants<br>* Hyaluronic acid (HyloGel) Hyaluronic acid and Ectoin (Hylo Dual Intense) Hyaluronic acid and Trehalos (Theloz Duo)<br>Procedure: Eye lid procedure<br>* Lid hygiene, warm eye bag, lid massage and Omega 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ocular Surface Disease Index (OSDI) | Change in Ocular Surface Disease Index (OSDI) evaluated at baseline and end of treatment. | Treatment period, up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of treatment related Adverse Events/Adverse Device Effects/Serious Adverse Events/Serious Adverse Device Effects and Unanticipated Serious Adverse Device Effects when using the Walther System. | Study period, up to 4.5 months | 
| Device Deficiencies | Number of Walther System Device Deficiencies. | Treatment period, up to 6 weeks | 
| Remission | Remission of estimated symptoms with OSDI after a treatment period of 6 weeks evaluated as a binary endpoint. | Treatment period, up to 6 weeks | 
| Non-Invasive Tear Break-Up time (NIBUT) | Degree of increased Non-Invasive tear Break-Up time. Baseline result compared to result measured during treatment period. | Treatment period, up to 6 weeks | 
| Schirmer's Test | Degree of improvement of tear production according to Schirmer's test. Baseline result compared to result measured during treatment period. | Treatment period, up to 6 weeks | 
| Tear Meniscus Height (TMH) | Degree of change in TMH value. Baseline value compared to value measured during treatment period. | Treatment period, up to 6 weeks | 
| Lissamine Green Test | Lissamine green test scale changes. Baseline scale compared with scale measured during treatment period. | Treatment period, up to 6 weeks | 
| Corneal Staining Test | Corneal Staining test scale changes. Baseline scale compared with scale measured during treatment period. | Treatment period, up to 6 weeks | 
| Lipid Layer Test | Degree of improvement of Lipid Layer coverage and thickness. Baseline result compared to results measured during the treatment period. The test is performed with a specific interference camera that visualizes the pre corneal lipid layer spread. The Interference colour chart allows quantification of the interference images, which are graded corresponding to lipid layer thickness and coverage. Images are classified from 5 grades; 1. Open meshwork, 2. Open to closed meshwork, 3. Closed to open meshwork, 4 Closed meshwork, 5. Colour fringe | Treatment period, up to 6 weeks | 
| Non-Invasive Tear Break-Up time (NIBUT) | Degree of increased Non-Invasive tear Break-Up time evaluated at 1 month after end of treatment period. | Follow-up period, up to 1 month | 
| Non-Invasive Tear Break-Up time (NIBUT) | Degree of increased Non-Invasive tear Break-Up time evaluated at 3 months after end of treatment period. | Follow-up period, up to 3 months | 
| Schirmer's Test | Degree of improvement of tear production according to Schirmer's test evaluated at 1 month after end of treatment period. | Follow-up period, up to 1 month | 
| Schirmer's Test | Degree of improvement of tear production according to Schirmer's test evaluated at 3 months after end of treatment period. | Follow-up period, up to 3 months | 
| Tear Meniscus Height (TMH) | Degree of change in TMH value evaluated at 1 month after end of treatment period. | Follow-up period, up to 1 month | 
| Tear Meniscus Height (TMH) | Degree of change in TMH value evaluated at 3 months after end of treatment period. | Follow-up period, up to 3 months | 
| Lissamine Green Test | Lissamine green test scale changes evaluated at 1 month after end of treatment period. | Follow-up period, up to 1 month | 
| Lissamine Green Test | Lissamine green test scale changes evaluated at 3 months after end of treatment period. | Follow-up period, up to 3 months | 
| Corneal Staining Test | Corneal Staining test scale changes evaluated at 1 month after end of treatment period. | Follow-up period, up to 1 month | 
| Corneal Staining Test | Corneal Staining test scale changes evaluated at 3 months after end of treatment period. | Follow-up period, up to 3 months | 
| Lipid Layer Test | Degree of improvement of Lipid Layer coverage and thickness evaluated at 1 month after end of treatment. The test is performed with a specific interference camera that visualizes the pre corneal lipid layer spread. The Interference colour chart allows quantification of the interference images, which are graded corresponding to lipid layer thickness and coverage. Images are classified from 5 grades; 1. Open meshwork, 2. Open to closed meshwork, 3. Closed to open meshwork, 4 Closed meshwork, 5. Colour fringe | Follow-up period, up to 1 month | 
| Lipid Layer Test | Degree of improvement of Lipid Layer coverage and thickness evaluated at 3 months after end of treatment. The test is performed with a specific interference camera that visualizes the pre corneal lipid layer spread. The Interference colour chart allows quantification of the interference images, which are graded corresponding to lipid layer thickness and coverage. Images are classified from 5 grades; 1. Open meshwork, 2. Open to closed meshwork, 3. Closed to open meshwork, 4 Closed meshwork, 5. Colour fringe | Follow-up period, up to 3 months | 
| Compliance | Grade of compliance/adherence to prescribed treatment. | Study period, up to 4.5 months |