CorneaINSTANTNCT03674892
Intranasal Neurostimulation in Ameliorating Symptoms of Neuropathic Corneal Pain
A study testing TrueTear™ intranasal neurostimulator (ITN) in people with Cornea, run by Tufts Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Cornea
- What is being tested?
- TrueTear™ intranasal neurostimulator (ITN)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2018to 9 Sep 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >22
- Ability to consent to study.
- Symptoms of neuropathic corneal pain for at least 3 months, such as burning, stinging, light sensitivity, discomfort or pain.
- Positive in vivo confocal microscopy (IVCM) findings for NCP such as presence of microneuromas and decreased nerve density.
- Fifty percent or more relief of pain or discomfort after instillation of Proparacaine eye drops as measured by the Visual Analogue Scale (VAS).
Who cannot join
- Clinically significant acute ocular surface diseases, such as active infectious keratitis or recent ocular surgery in the past 3 months.
- Chronic or recurrent epistaxis, coagulation disorders.
- Nasal or sinus surgery or significant trauma to the nose.
- Severe nasal airway obstruction or vascularized nasal polyps.
- Cardiac demand pacemaker, implanted defibrillator, or other implanted electronic device in the head or neck.
- Chronic or recurrent nosebleeds
Show all 9Show fewer
- Bleeding disorder
- Known hypersensitivity (allergy) to the hydrogel material
- Disabling arthritis, neuropathy, or limited motor coordination affecting self-handling of the device.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessing the Efficacy of Intranasal Neurostimulation in Ameliorating Symptoms of Neuropathic Corneal Pain
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.
Read the 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:
- To elucidate the efficacy of ITN in ameliorating pain among neuropathic corneal pain patients.
- To elucidate the safety, efficacy, longevity of ITN in ameliorating pain among neuropathic corneal pain patients during a 90-day period with daily use.
- To assess quality of life changes by treating neuropathic corneal pain with ITN during a 90-day period with daily use.
- Conditions
- Cornea
- Being tested
- TrueTear™ intranasal neurostimulator (ITN)
- Keywords
- Intranasal Neurostimulation
- Medical subject headings
- Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrueTear™ intranasal neurostimulator (ITN)Device
TrueTear™ intranasal neurostimulator (ITN)
| Study group | Role | What they receive |
|---|---|---|
| TrueTear™ intranasal neurostimulator (ITN) | Experimental | TrueTear™ intranasal neurostimulator (ITN) Receives: Device: TrueTear™ intranasal neurostimulator (ITN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: immediately before and after ITN on Day 1 (baseline)
Secondary outcomes (12)
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.
Measured: immediately before and after ITN on Day 45
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.
Measured: immediately before and after ITN on Day 90
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.
Measured: Day 1 (Baseline)
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.
Measured: 45 days
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.
Measured: 90 days
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.
Measured: Baseline vs day 45 visit and Baseline vs day 90 visit
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.
Measured: Baseline vs day 45 visit and Baseline vs day 90 visit
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.
Measured: Baseline vs day 45 visit and Baseline vs day 90 visit
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.
Measured: Baseline vs day 45 visit and Baseline vs day 90 visit
Number of Participants With Adverse Events (Safety)
For safety analyses during the study, patient-reported adverse events that developed after intranasal neurostimulation were recorded.
Measured: 90 days
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.
Measured: 90 days
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.
Measured: Baseline vs 45 Day Visit and baseline vs 90 Day Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2018
- Study start28 Sep 2018
- Primary completion9 Sep 2022
- Study completion9 Sep 2023
Why it stopped: Original device is now discontinued; we are changing the study device shortly
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CorneaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- non-randomized, open-label, single arm pilot trial
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pedram Hamrah, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03674892
- Sponsor's protocol ID
- 12978
- Acronym
- INSTANT
- Status last verified
- Aug 2025
- First submitted
- 12 Sep 2018
- Last updated
- 24 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Efficacy of Intranasal Neurostimulation in Ameliorating Symptoms of Neuropathic Corneal Pain
- ClinicalTrials.gov ID
- NCT03674892
- Acronym / sponsor ID
- INSTANT / 12978
- Conditions
- Cornea
- Keywords
- Intranasal Neurostimulation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Original device is now discontinued; we are changing the study device shortly
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Study start
- 28 Sep 2018 (actual)
- Primary completion
- 9 Sep 2022 (actual)
- Study completion
- 9 Sep 2023 (actual)
- First posted
- 18 Sep 2018 (actual)
- Results
- Posted 24 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To elucidate the efficacy of ITN in ameliorating pain among neuropathic corneal pain patients.
- To elucidate the safety, efficacy, longevity of ITN in ameliorating pain among neuropathic corneal pain patients during a 90-day period with daily use.
- To assess quality of life changes by treating neuropathic corneal pain with ITN during a 90-day period with daily use.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- non-randomized, open-label, single arm pilot trial
| Arm | Type | Receives |
|---|---|---|
| TrueTear™ intranasal neurostimulator (ITN) | Experimental | Device: TrueTear™ intranasal neurostimulator (ITN)TrueTear™ intranasal neurostimulator (ITN) |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >22
- Ability to consent to study.
- Symptoms of neuropathic corneal pain for at least 3 months, such as burning, stinging, light sensitivity, discomfort or pain.
- Positive in vivo confocal microscopy (IVCM) findings for NCP such as presence of microneuromas and decreased nerve density.
- Fifty percent or more relief of pain or discomfort after instillation of Proparacaine eye drops as measured by the Visual Analogue Scale (VAS).
Key exclusion criteria (9 listed)
- Clinically significant acute ocular surface diseases, such as active infectious keratitis or recent ocular surgery in the past 3 months.
- Chronic or recurrent epistaxis, coagulation disorders.
- Nasal or sinus surgery or significant trauma to the nose.
- Severe nasal airway obstruction or vascularized nasal polyps.
- Cardiac demand pacemaker, implanted defibrillator, or other implanted electronic device in the head or neck.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrueTear™ intranasal neurostimulator (ITN)TrueTear™ intranasal neurostimulator (ITN) | Device | TrueTear™ intranasal neurostimulator (ITN) |
Primary outcome
Change to Overall Pain by the Visual Analogue Scale (VAS) After Intranasal Neurostimulator (ITN) Stimulation at Baseline
Time frame: 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.
12 secondary outcomes
Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 45-day Period
Time frame: immediately before and after ITN on Day 45
Change to Overall Pain by the Visual Analogue Scale (VAS) After Daily Intranasal Neurostimulator (ITN) Stimulation Over 90-day Period
Time frame: immediately before and after ITN on Day 90
Quality of Life as Measured With OPAS at Baseline
Time frame: Day 1 (Baseline)
Quality of Life as Measured Daily With OPAS at 45 Days
Time frame: 45 days
Quality of Life as Measured Daily With OPAS at 90 Days
Time frame: 90 days
Overall Change in Quality of Life as Measured Daily With OPAS
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Percent Change From Pain Level Dimension Questions of the Ocular Pain Assessment Survey (OPAS)
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Overall Percent Change on Impact of Dry Eye in Everyday Life (IDEEL)
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Change in the Intraocular Pressure (IOP) Measured in Each Visit.
Time frame: Baseline vs day 45 visit and Baseline vs day 90 visit
Number of Participants With Adverse Events (Safety)
Time frame: 90 days
Number of Participants With Adverse Events (Tolerability)
Time frame: 90 days
Reduction on Other Concomitant Pain Therapy
Time frame: Baseline vs 45 Day Visit and baseline vs 90 Day Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pedram Hamrah, MD principal investigator
Tufts Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TrueTear™ intranasal neurostimulator (ITN) in people with Cornea, run by Tufts Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change to Overall Pain by the Visual Analogue Scale (VAS) After Intranasal Neurostimulator (ITN) Stimulation at Baseline (time frame: immediately before and after ITN on Day 1 (baseline)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.