Cornea
Conditions
Keywords
Intranasal Neurostimulation
Brief summary
This study is a prospective, interventional, open-label, single arm, non-randomized trial treating 30 patients with peripheral or mixed neuropathic corneal pain at their baseline exam and following 45 days and 90 days of daily use with the TrueTear™ ITN device.
Detailed description
The investigators hypothesize that the stimulation through the ethmoidal nerve in the nasal cavity may have an inhibitory effect on the primary TG interneurons and block the ocular pain signaling to the brain. The investigators propose a non-randomized, open-label, single arm pilot trial for treatment of neuropathic corneal pain (NCP) with ITN with the following specific aims: Specific Aims: 1. To elucidate the efficacy of ITN in ameliorating pain among neuropathic corneal pain patients. 2. To elucidate the safety, efficacy, longevity of ITN in ameliorating pain among neuropathic corneal pain patients during a 90-day period with daily use. 3. To assess quality of life changes by treating neuropathic corneal pain with ITN during a 90-day period with daily use.
Interventions
TrueTear™ intranasal neurostimulator (ITN)
Sponsors
Tufts Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
non-randomized, open-label, single arm pilot trial
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>22 2. Ability to consent to study. 3. Symptoms of neuropathic corneal pain for at least 3 months, such as burning, stinging, light sensitivity, discomfort or pain. 4. Positive in vivo confocal microscopy (IVCM) findings for NCP such as presence of microneuromas and decreased nerve density. 5. Fifty percent or more relief of pain or discomfort after instillation of Proparacaine eye drops as measured by the Visual Analogue Scale (VAS).
Exclusion criteria
1. Clinically significant acute ocular surface diseases, such as active infectious keratitis or recent ocular surgery in the past 3 months. 2. Chronic or recurrent epistaxis, coagulation disorders. 3. Nasal or sinus surgery or significant trauma to the nose. 4. Severe nasal airway obstruction or vascularized nasal polyps. 5. Cardiac demand pacemaker, implanted defibrillator, or other implanted electronic device in the head or neck. 6. Chronic or recurrent nosebleeds 7. Bleeding disorder 8. Known hypersensitivity (allergy) to the hydrogel material 9. Disabling arthritis, neuropathy, or limited motor coordination affecting self-handling of the device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change to Overall Pain by the Visual Analogue Scale (VAS) After Intranasal Neurostimulator (ITN) Stimulation at Baseline | immediately before and after ITN on Day 1 (baseline) | The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 90-day Period | immediately before and after ITN on Day 90 | The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome. |
| Quality of Life as Measured With OPAS at Baseline | Day 1 (Baseline) | The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL. |
| Quality of Life as Measured Daily With OPAS at 45 Days | 45 days | The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL. |
| Quality of Life as Measured Daily With OPAS at 90 Days | 90 days | The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL. |
| Overall Change in Quality of Life as Measured Daily With OPAS | Baseline vs day 45 visit and Baseline vs day 90 visit | The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Percentage changes in the scores between baseline vs 45-day visit and baseline vs 90-day visit after daily intranasal neurostimulation are given below. |
| Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 45-day Period | immediately before and after ITN on Day 45 | The VAS is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome. |
| Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Baseline vs day 45 visit and Baseline vs day 90 visit | IDEEL Quality of Life Questionnaire is a 27-item questionnaire, designed specifically for DED and is divided into three parts. It assesses the quality of life in three aspects of life for the previous 2 weeks: daily activities, work and feelings. The quality of life is assessed on a scale of 0-5, with zero being inability to do the activity. The score is calculated between 0 - 100 with higher scores indicating a better quality of life. Percentage change in IDEEL questionnaire subheading between baseline and day 45 and baseline and day 90 were given below. |
| Change in the Intraocular Pressure (IOP) Measured in Each Visit. | Baseline vs day 45 visit and Baseline vs day 90 visit | Intraocular pressure will be measured by an applanation tonometer used on slit lamp (Goldmann) in mmHg. Change in IOP values between baseline and 90-day is provided below. A healthy eye pressure is between 10 and 21 millimeters of mercury. The differences in intraocular pressure between the baseline and day 45 visits, as well as between the baseline and day 90 visits, are presented below. |
| Number of Participants With Adverse Events (Safety) | 90 days | For safety analyses during the study, patient-reported adverse events that developed after intranasal neurostimulation were recorded. |
| Number of Participants With Adverse Events (Tolerability) | 90 days | Tolerability of Intranasal Neurostimulator (ITN) was evaluated by using Ocular Tolerability and Compliance Questionnaire. It assesses symptoms of discomfort in each eye after ITN use. |
| Reduction on Other Concomitant Pain Therapy | Baseline vs 45 Day Visit and baseline vs 90 Day Visit | After daily intranasal neurostimulation, the change in the number of systemic pain medication between baseline vs 45-day visit and Baseline vs 90-day visit was evaluated. |
| Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Baseline vs day 45 visit and Baseline vs day 90 visit | The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. Eye pain intensity was assessed using a numerical scale (0-10) for the most, least, and average pain in the past 24 hours and 2 weeks. Higher scores indicate severe pain of OPAS questionnaire. The percent changes in pain intensity between baseline vs 45-day and baseline vs 90-day are provided below. |
Countries
United States
Participant flow
Pre-assignment details
As outlined in the study protocol, this trial aimed to enroll 45 patients with neuropathic corneal pain and evaluate them at 45 and 90 days following daily use of the TrueTear™ device. However, due to the COVID-19 pandemic and related concerns about infection, only 21 patients enrolled in the study and completed the first visit. As this was a single arm study, all participants were assigned to the TrueTear™ intranasal neurostimulator (ITN) group.
Participants by arm
| Arm | Count |
|---|---|
| TrueTear™ Intranasal Neurostimulator (ITN) TrueTear™ intranasal neurostimulator (ITN)
TrueTear™ intranasal neurostimulator (ITN): TrueTear™ intranasal neurostimulator (ITN) | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Excessive Tearing | 1 |
| Overall Study | Increased Eye Pain | 1 |
| Overall Study | Increased Facial Pain | 1 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Migraine | 2 |
| Overall Study | Sinus Infection | 1 |
| Overall Study | Sinus Irritation | 1 |
Baseline characteristics
| Characteristic | TrueTear™ Intranasal Neurostimulator (ITN) | — |
|---|---|---|
| Age, Continuous | 53.05 years STANDARD_DEVIATION 14.82 | — |
| Best Corrected Visual Acuity | 0.09 logMAR STANDARD_DEVIATION 0.1 | — |
| Cold Saline Test After | 2.75 units on a scale STANDARD_DEVIATION 2.24 | — |
| Cold Saline Test Before | 4.40 units on a scale STANDARD_DEVIATION 2.21 | — |
| Conjunctival Staining Score | 2.44 Scores on a scale STANDARD_DEVIATION 4.03 | — |
| Corneal Staining Score | 2.56 scores on a scale STANDARD_DEVIATION 4.03 | — |
| Filter Glasses Test | 78.00 Units on a scale (0-100) STANDARD_DEVIATION 8.36 | — |
| Hypertonic Test After | 5.25 units on a scale STANDARD_DEVIATION 3.53 | — |
| Hypertonic Test Before | 3.30 units on a scale STANDARD_DEVIATION 2.79 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Being around and/or using scented products | 3.21 Scores on a Scale STANDARD_DEVIATION 1.96 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Doing close work in the evening or at night | 2.73 Scores on a Scale STANDARD_DEVIATION 1.43 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Doing close work in the morning or afternoon | 2.60 Scores on a Scale STANDARD_DEVIATION 1.59 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Driving | 3.35 Scores on a Scale STANDARD_DEVIATION 1.64 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Flying on an airplane | 3.53 Scores on a Scale STANDARD_DEVIATION 1.71 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Going somewhere where there is tobacco smoke | 2.40 Scores on a Scale STANDARD_DEVIATION 1.91 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Wearing contact lenses | 3.92 Scores on a Scale STANDARD_DEVIATION 2.05 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Wearing make-up | 2.57 Scores on a Scale STANDARD_DEVIATION 1.86 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Daily Activities Working on a computer | 2.46 Scores on a Scale STANDARD_DEVIATION 1.68 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling annoyed | 1.93 Scores on a Scale STANDARD_DEVIATION 1.22 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling different from other people | 1.66 Scores on a Scale STANDARD_DEVIATION 1.63 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling like I am always aware of my eyes | 0.80 Scores on a Scale STANDARD_DEVIATION 1.08 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling like I have to make adjustments to my life | 1.06 Scores on a Scale STANDARD_DEVIATION 1.12 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling like my eyes do not look nice | 1.66 Scores on a Scale STANDARD_DEVIATION 1.44 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling like people look at me and think I am fine when I'm not | 1.73 Scores on a Scale STANDARD_DEVIATION 1.66 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling like there is nothing I can do for my dry eyes | 1.26 Scores on a Scale STANDARD_DEVIATION 1.38 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling older than I really am | 2.00 Scores on a Scale STANDARD_DEVIATION 1.64 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Feeling sad | 1.80 Scores on a Scale STANDARD_DEVIATION 1.2 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Impatience | 2.13 Scores on a Scale STANDARD_DEVIATION 1.12 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Irritability | 1.73 Scores on a Scale STANDARD_DEVIATION 1.03 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Feelings Worry that my dry eyes will get worse | 1.33 Scores on a Scale STANDARD_DEVIATION 1.32 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Situations at Work Feeling distracted | 1.64 IDEEL Score STANDARD_DEVIATION 1 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Situations at Work Feeling like I couldn't concentrate | 1.71 IDEEL Score STANDARD_DEVIATION 1.06 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Situations at Work Having to change my work environment | 1.28 IDEEL Score STANDARD_DEVIATION 1.58 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Situations at Work Having to change the way I work | 1.28 IDEEL Score STANDARD_DEVIATION 1.26 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Situations at Work Having to take a break from work | 1.38 IDEEL Score STANDARD_DEVIATION 1.12 | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Work No | 5 Participants | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Work No answer | 6 Participants | — |
| Impact of Dry Eye in Everyday Life (IDEEL) Work Yes | 10 Participants | — |
| Intraocular Pressure | 13.76 millimeters of mercury (mmHg) STANDARD_DEVIATION 3.22 | — |
| Neuropathic Corneal Pain Type Mixed | 5 Participants | — |
| Neuropathic Corneal Pain Type Peripheral | 16 Participants | — |
| Ocular Pain Assessment Survey (OPAS) | 46.68 The percentage of time (%) STANDARD_DEVIATION 36.9 | — |
| Ocular Pain Assessment Survey (OPAS) Aggravating Factors Volatile chemicals (cleaning agents, fumes, cosmetic) | 65.00 percent (%) STANDARD_DEVIATION 38.17 | — |
| Ocular Pain Assessment Survey (OPAS) Aggravating Factors Wind, dry air, heat, air conditioning | 79.72 percent (%) STANDARD_DEVIATION 32.47 | — |
| Ocular Pain Assessment Survey (OPAS) Associated Factors Burning | 73.00 percent (%) STANDARD_DEVIATION 25.15 | — |
| Ocular Pain Assessment Survey (OPAS) Associated Factors Redness | 50.26 percent (%) STANDARD_DEVIATION 34.74 | — |
| Ocular Pain Assessment Survey (OPAS) Associated Factors Sensitivity to light | 75.25 percent (%) STANDARD_DEVIATION 36.65 | — |
| Ocular Pain Assessment Survey (OPAS) Associated Factors Tearing | 38.95 percent (%) STANDARD_DEVIATION 36.99 | — |
| Ocular Pain Assessment Survey (OPAS) Average Quality of Life (QoL) Score: | 6.46 Scores on a scale STANDARD_DEVIATION 2.48 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Average Eye Pain Intensity in the past 24 hours | 5.75 Scores on a scale STANDARD_DEVIATION 1.96 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Average Eye Pain Intensity in the past 2 weeks | 5.65 Scores on a scale STANDARD_DEVIATION 1.96 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Least Eye Pain Intensity in the past 24 hours | 3.21 Scores on a scale STANDARD_DEVIATION 2.1 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Least Eye Pain Intensity in the past 2 weeks | 4.00 Scores on a scale STANDARD_DEVIATION 2.29 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Most Eye Pain Intensity in the past 24 hours | 7.87 Scores on a scale STANDARD_DEVIATION 1.99 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Most Eye Pain Intensity in the past 2 weeks | 7.82 Scores on a scale STANDARD_DEVIATION 2.02 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Non-Eye Pain in the past 24 hours | 4.68 Scores on a scale STANDARD_DEVIATION 3.64 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Non-Eye Pain in the past 2 weeks | 5.42 Scores on a scale STANDARD_DEVIATION 3.92 | — |
| Ocular Pain Assessment Survey (OPAS) Dimensions Overall Pain | 5.50 Scores on a scale STANDARD_DEVIATION 2.42 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters Driving | 6.50 Scores on a scale STANDARD_DEVIATION 3.31 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters Enjoying Life/ Relations with other people | 6.65 Scores on a scale STANDARD_DEVIATION 3.26 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters General activity (walking, doing house chores) | 5.52 Scores on a scale STANDARD_DEVIATION 3.31 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters Mood | 7.00 Scores on a scale STANDARD_DEVIATION 2.45 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters Reading | 7.37 Scores on a scale STANDARD_DEVIATION 2.88 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters Sleep | 4.55 Scores on a scale STANDARD_DEVIATION 3.28 | — |
| Ocular Pain Assessment Survey (OPAS) Quality of Life Parameters | 74.12 The percentage of time (%) STANDARD_DEVIATION 27.9 | — |
| Ocular Pain Assessment Survey (OPAS) Symptom Relief Eye Pain | 33.63 percent (%) STANDARD_DEVIATION 23.03 | — |
| Ocular Pain Assessment Survey (OPAS) Symptom Relief Non-Eye Pain (face/head) | 23.75 percent (%) STANDARD_DEVIATION 27.61 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Areas with Air Conditioner | 3.64 Scores on a scale STANDARD_DEVIATION 0.63 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Blurred Eyes | 2.30 Scores on a scale STANDARD_DEVIATION 1.49 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Driving Night | 2.50 Scores on a scale STANDARD_DEVIATION 1.54 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Gritty | 2.37 Scores on a scale STANDARD_DEVIATION 1.3 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Light Sensitivity | 2.85 Scores on a scale STANDARD_DEVIATION 1.56 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Low Humidity | 3.53 Scores on a scale STANDARD_DEVIATION 0.62 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Painful Eyes | 3.30 Scores on a scale STANDARD_DEVIATION 0.86 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Poor Vision | 2.26 Scores on a scale STANDARD_DEVIATION 1.36 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Reading | 2.61 Scores on a scale STANDARD_DEVIATION 0.97 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Watching TV | 2.94 Scores on a scale STANDARD_DEVIATION 2.01 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Windy Conditions | 3.17 Scores on a scale STANDARD_DEVIATION 1.15 | — |
| Ocular Surface Disease Index (OSDI) Dimensions Working ATM/Computer | 3.11 Scores on a scale STANDARD_DEVIATION 1.13 | — |
| Ocular Surface Disease Index (OSDI) Score | 69.96 Scores on a scale STANDARD_DEVIATION 19.83 | — |
| Pain Intensity Difference | -3.81 units on a scale STANDARD_DEVIATION 1.88 | — |
| Pain Intensity Post-stimulation | 1.92 units on a scale STANDARD_DEVIATION 1.67 | — |
| Pain Intensity Pre-stimulation | 5.73 units on a scale STANDARD_DEVIATION 2.09 | — |
| Pain Intensity Change Percent after Intranasal Neurostimulation | -66.49 percent change STANDARD_DEVIATION 29.38 | — |
| Proparacaine Challenge Test After | 1.80 Units on a scale STANDARD_DEVIATION 1.54 | — |
| Proparacaine Challenge Test Before | 5.80 Units on a scale STANDARD_DEVIATION 3.08 | — |
| Proparacaine Challenge Test Percent Change | -68.96 percentage change STANDARD_DEVIATION 19.12 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Randomly Selected Eye for Analysis (Right eye/Left eye) Left eye OS | 10 Participants | — |
| Randomly Selected Eye for Analysis (Right eye/Left eye) Right eye OD | 11 Participants | — |
| Region of Enrollment United States | 21 participants | — |
| Schirmer | 8.71 millimeters STANDARD_DEVIATION 7 | — |
| Sex: Female, Male Female | 18 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
| Tear Break Up Time | 6.70 seconds STANDARD_DEVIATION 2.69 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 13 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Change to Overall Pain by the Visual Analogue Scale (VAS) After Intranasal Neurostimulator (ITN) Stimulation at Baseline
The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.
Time frame: immediately before and after ITN on Day 1 (baseline)
Population: Post-stimulation minus pre-stimulation pain scores of all patients who underwent intranasal neurostimulation at the 1-day (baseline) visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Participated Baseline Visit | Change to Overall Pain by the Visual Analogue Scale (VAS) After Intranasal Neurostimulator (ITN) Stimulation at Baseline | -3.81 score on a scale | Standard Error 0.41 |
Secondary
Change in the Intraocular Pressure (IOP) Measured in Each Visit.
Intraocular pressure will be measured by an applanation tonometer used on slit lamp (Goldmann) in mmHg. Change in IOP values between baseline and 90-day is provided below. A healthy eye pressure is between 10 and 21 millimeters of mercury. The differences in intraocular pressure between the baseline and day 45 visits, as well as between the baseline and day 90 visits, are presented below.
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Population: Patients participated INSTANT study visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Participated Baseline Visit | Change in the Intraocular Pressure (IOP) Measured in Each Visit. | -0.18 millimeters of mercury (mmHg) | Standard Error 1.1 |
| Baseline vs 90-day Visit | Change in the Intraocular Pressure (IOP) Measured in Each Visit. | -0.43 millimeters of mercury (mmHg) | Standard Error 0.92 |
Secondary
Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 45-day Period
The VAS is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.
Time frame: immediately before and after ITN on Day 45
Population: Post-stimulation minus pre-stimulation pain scores of all patients who underwent intranasal neurostimulation at the 45-day visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Participated Baseline Visit | Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 45-day Period | -1.58 score on a scale | Standard Error 0.39 |
Secondary
Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 90-day Period
The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.
Time frame: immediately before and after ITN on Day 90
Population: Post-stimulation minus pre-stimulation pain scores of all patients who underwent intranasal neurostimulation at the 90-day visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Participated Baseline Visit | Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 90-day Period | -0.75 score on a scale | Standard Error 0.83 |
Secondary
Number of Participants With Adverse Events (Safety)
For safety analyses during the study, patient-reported adverse events that developed after intranasal neurostimulation were recorded.
Time frame: 90 days
Population: All patients who underwent intranasal neurostimulation were evaluated for safety measures.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Excessive Tearing | 1 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Migraine Attacks | 2 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Increased Eye Pain | 1 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Increased Facial Pain | 1 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Sinus Irritation and Pain | 1 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Sinus Infection | 1 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Safety) | Pain in the nose | 2 Participants |
Secondary
Number of Participants With Adverse Events (Tolerability)
Tolerability of Intranasal Neurostimulator (ITN) was evaluated by using Ocular Tolerability and Compliance Questionnaire. It assesses symptoms of discomfort in each eye after ITN use.
Time frame: 90 days
Population: All patients who underwent intranasal neurostimulation and completed Ocular Tolerability and Compliance Questionnaire.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Tolerability) | Eye Itching | 2 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Tolerability) | Burning sensation | 3 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Tolerability) | Foreign Body Sensation | 2 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Tolerability) | Sneezing | 2 Participants |
| All Patients Participated Baseline Visit | Number of Participants With Adverse Events (Tolerability) | Forehead Throbbing | 1 Participants |
Secondary
Overall Change in Quality of Life as Measured Daily With OPAS
The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Percentage changes in the scores between baseline vs 45-day visit and baseline vs 90-day visit after daily intranasal neurostimulation are given below.
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Population: Patients participated INSTANT study visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | General Activity | -26.99 percent change | Standard Error 30.92 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Sleep | -23.95 percent change | Standard Error 30.32 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Driving and/or watching TV | -22.61 percent change | Standard Error 11.97 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Enjoying life/ Relationship | -26.46 percent change | Standard Error 13.94 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Mood | -22.57 percent change | Standard Error 9.2 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Time spent thinking about pain | -19.56 percent change | Standard Error 34.5 |
| All Patients Participated Baseline Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Reading and/or computer use | -25.37 percent change | Standard Error 11.39 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Time spent thinking about pain | -28.07 percent change | Standard Error 25.72 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Reading and/or computer use | -34.87 percent change | Standard Error 17.72 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Driving and/or watching TV | -23.07 percent change | Standard Error 19.32 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | General Activity | -54.71 percent change | Standard Error 15.02 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Mood | -37.14 percent change | Standard Error 10.84 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Sleep | -56.04 percent change | Standard Error 40.44 |
| Baseline vs 90-day Visit | Overall Change in Quality of Life as Measured Daily With OPAS | Enjoying life/ Relationship | -35.33 percent change | Standard Error 26.2 |
Secondary
Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL)
IDEEL Quality of Life Questionnaire is a 27-item questionnaire, designed specifically for DED and is divided into three parts. It assesses the quality of life in three aspects of life for the previous 2 weeks: daily activities, work and feelings. The quality of life is assessed on a scale of 0-5, with zero being inability to do the activity. The score is calculated between 0 - 100 with higher scores indicating a better quality of life. Percentage change in IDEEL questionnaire subheading between baseline and day 45 and baseline and day 90 were given below.
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Population: All patients participated INSTANT visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Daily Activities | 16.14 percent change | Standard Error 23.72 |
| All Patients Participated Baseline Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Feelings | 17.06 percent change | Standard Error 17.38 |
| All Patients Participated Baseline Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Work | 46.91 percent change | Standard Error 17.82 |
| Baseline vs 90-day Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Daily Activities | 21.83 percent change | Standard Error 17.93 |
| Baseline vs 90-day Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Feelings | 40.73 percent change | Standard Error 38.43 |
| Baseline vs 90-day Visit | Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL) | Work | 48.80 percent change | Standard Error 40.45 |
Secondary
Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS)
The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. Eye pain intensity was assessed using a numerical scale (0-10) for the most, least, and average pain in the past 24 hours and 2 weeks. Higher scores indicate severe pain of OPAS questionnaire. The percent changes in pain intensity between baseline vs 45-day and baseline vs 90-day are provided below.
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Population: Patients participated INSTANT study visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Most eye pain in 24 hours | -31.76 percent change | Standard Error 18.76 |
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Least eye pain in 24 hours | -12.14 percent change | Standard Error 22.67 |
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Average eye pain in 24 hours | -30.43 percent change | Standard Error 20.17 |
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Most eye pain in 2 weeks | -22.89 percent change | Standard Error 18.43 |
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Least eye pain in 2 weeks | -19.75 percent change | Standard Error 25.93 |
| All Patients Participated Baseline Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Average eye pain in 2 weeks | -24.77 percent change | Standard Error 22.18 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Least eye pain in 2 weeks | -37.50 percent change | Standard Error 26.93 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Most eye pain in 24 hours | -54.25 percent change | Standard Error 20.55 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Most eye pain in 2 weeks | -43.73 percent change | Standard Error 16.57 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Least eye pain in 24 hours | -37.69 percent change | Standard Error 25.46 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Average eye pain in 2 weeks | -46.90 percent change | Standard Error 20.85 |
| Baseline vs 90-day Visit | Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS) | Average eye pain in 24 hours | -46.08 percent change | Standard Error 21.35 |
Secondary
Quality of Life as Measured Daily With OPAS at 45 Days
The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL.
Time frame: 45 days
Population: All Patients Participated 45 Day Visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Reading and/or computer use | 5.50 score on a scale | Standard Error 0.85 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Driving and/or watching TV | 5.03 score on a scale | Standard Error 0.96 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | General Activity | 4.03 score on a scale | Standard Error 0.8 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Mood | 5.42 score on a scale | Standard Error 0.74 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Sleep | 3.64 score on a scale | Standard Error 0.9 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Enjoying Life/ Relationship | 4.89 score on a scale | Standard Error 0.7 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 45 Days | Time spent thinking about pain | 59.6 score on a scale | Standard Error 8.91 |
Secondary
Quality of Life as Measured Daily With OPAS at 90 Days
The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL.
Time frame: 90 days
Population: All Patients Participated 90 Day Visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Reading and/or computer use | 4.80 score on a scale | Standard Error 1.82 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Driving and/or watching TV | 5.00 score on a scale | Standard Error 1.92 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | General activity | 2.50 score on a scale | Standard Error 0.89 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Mood | 4.40 score on a scale | Standard Error 1.37 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Sleep | 2.00 score on a scale | Standard Error 1.37 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Enjoying Life/ Relationship | 4.30 score on a scale | Standard Error 1.57 |
| All Patients Participated Baseline Visit | Quality of Life as Measured Daily With OPAS at 90 Days | Time spent thinking about pain | 53.31 score on a scale | Standard Error 26.01 |
Secondary
Quality of Life as Measured With OPAS at Baseline
The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the Reading and/or computer use, Driving and/or watching TV, General Activity, Mood, Sleep, Enjoying Life/ Relationship. Time spent thinking about pain dimensions and 0-100. Higher scores indicate worse QoL.
Time frame: Day 1 (Baseline)
Population: All Patients Participated 1 Day (Baseline) Visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Reading and/or computer use | 7.37 score on a scale | Standard Error 0.64 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Driving and/or watching tv | 6.50 score on a scale | Standard Error 0.78 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | General activity | 5.52 score on a scale | Standard Error 0.75 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Mood | 7.00 score on a scale | Standard Error 0.54 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Sleep | 4.55 score on a scale | Standard Error 0.77 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Enjoying Life/Relationship | 6.65 score on a scale | Standard Error 0.73 |
| All Patients Participated Baseline Visit | Quality of Life as Measured With OPAS at Baseline | Time spent thinking about pain | 74.12 score on a scale | Standard Error 6.76 |
Secondary
Reduction on Other Concomitant Pain Therapy
After daily intranasal neurostimulation, the change in the number of systemic pain medication between baseline vs 45-day visit and Baseline vs 90-day visit was evaluated.
Time frame: Baseline vs 45 Day Visit and baseline vs 90 Day Visit
Population: INSTANT patients participated baseline-45 Day Visit and baseline-90 Day Visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Participated Baseline Visit | Reduction on Other Concomitant Pain Therapy | 0.14 Number of medication (n) | Standard Error 0.08 |
| Baseline vs 90-day Visit | Reduction on Other Concomitant Pain Therapy | -0.25 Number of medication (n) | Standard Error 0.25 |