Back to resultsQST for Corneal Nerve Function
Primary Purpose
Corneal Disease, Neuropathy, Dry Eye Disease
Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Quantitative Sensory Test
Sponsored by
About this trial
This is an interventional treatment trial for Corneal Disease focused on measuring Quantitative Sensory Test
Eligibility Criteria
Inclusion Criteria: Group 1: Stage I Neurotrophic Keratopathy (NK) Clinical findings of Stage I NK Decreased nerve density by IVCM Decreased corneal sensation Group 2: Stage II NK Clinical findings of Stage II NK Decreased nerve density by IVCM Decreased corneal sensation Group 3: Dry Eye Disease (DED) Symptoms of DED at least 3 months Presence of at least one of the following DED signs; tear film break-up time lower than 7, ocular surface staining more than +1 based on NIH scale Normal or mildly effected corneal sensation Group 4: Healthy Individuals Absence of any ocular surface symptoms Absence of ocular surface findings Transparent and clear cornea Normal corneal sensation Group 5: NCP Presence of neuropathic symptoms AND Symptoms out of proportion to clinical findings AND Nerve abnormalities detected by in vivo confocal microscopy Exclusion Criteria: History of diabetes History of ocular surgery, corneal infection, or corneal injury within the last 3 months Systemic regular anti-inflammatory and/or steroid and/or immune-modulatory therapy in the last 3 months Active ocular allergies Any major psychiatric illness including bipolar, psychosis, obsessive-compulsive disorder and major depression Pregnancy History of surgery within the last 3 months History of , sarcoidosis, GVHD or collagen vascular disease Allergic to benzalkonium chloride "BAK" (an eye-drop preservative) Concurrent enrollment in other studies that in the opinion of the investigator will interfere with the results of this study Non-English speakers
Sites / Locations
- Tufts Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Stage I Neurotrophic Keratopathy
Stage II Neurotrophic Keratopathy
Dry Eye Disease
Healthy Individuals
Arm Description
Clinical findings of corneal hyperplasia and irregularity, scattered small facets of dried epithelium, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.
Clinical findings of corneal epithelial defect with smooth and rolled edges, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.
Symptoms of dry eye disease for at least 3 months, supported by clinical finding of decreased tear film break-up time or ocular surface staining. Normal corneal sensation.
Absence of any ocular symptoms, absence of surface findings (including corneal or conjunctival staining, corneal scar or surgical wound), and normal corneal sensation.
Outcomes
Primary Outcome Measures
Thermal stimulus response to QST on site of trigeminal nerve first branch, as assessed by cold detection threshold (CDT) and hot detection threshold (HDT)
Cold and heat sensation thresholds will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken for each stimuli. Participants will receive successive ramps of gradually decreasing or increasing temperature, starting from a resting neutral temperature of 32°C. Participants will be instructed to press a response button when a thermal sensation (either cold or warm) is perceived.
Mechanical stimulus response to QST on site of trigeminal nerve first branch, as assessed by vibration detection threshold (VDT)
Vibration sensation threshold will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken. Participants will receive successive ramps of gradually decreasing or increasing vibration, starting from. Participants will be instructed to press a response button when a mechanical sensation is perceived.
Differences in thermal stimulus pain threshold across the 4 study arms
Cold pain threshold (CPT) and heat pain threshold (HPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from probe on QST testing
Differences in mechanical stimulus pain threshold across the 4 study arms
Vibration pain threshold (VPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from vibration probe on QST testing
Secondary Outcome Measures
To correlate the QST responses with morphological changes of corneal nerves detected by IVCM
In vivo confocal microscopy (IVCM) imaging will be performed to observe for any morphological nerve changes; such as decreased nerve density, nerve tortuosity presence of microneuromas.
To correlate symptom severity as assessed by the Ocular Surface Disease Index (OSDI), to stimulus response across the 4 interventional arms.
Ocular Surface Disease Index (OSDI) questionnaire A 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. The 12 items of the OSDI questionnaire are graded on a scale of 0 to 4, where 0 indicates none of the time; 1, some of the time; 2, half of the time; 3, most of the time; and 4, all of the time. The total OSDI score is then calculated on the basis of the following formula: OSDI= [(sum of scores for all questions answered) x 100]/[(total number of questions answered) x 4]. Higher OSDI scores represent greater severity of symptoms.
To compare QST response differences between trigeminal nerve first branch and forearm in patients.
Measurement of stimuli detection thresholds, pain thresholds and pain ranges for different stimuli (cold, heat and vibration) type in study groups at 3 different periocular sites (just below supraorbital notch, lateral canthus, inferior orbital bone; 1 cm lateral of medial canthus) and non-dominant hand hypothenar eminence (as a reference site)
Full Information
NCT ID
NCT05758753
First Posted
September 6, 2022
Last Updated
June 11, 2023
Sponsor
Tufts Medical Center
Collaborators
Dompé Farmaceutici S.p.A
1. Study Identification
Unique Protocol Identification Number
NCT05758753
Brief Title
QST for Corneal Nerve Function
Official Title
The Efficacy of Quantitative Sensory Test (QST) in Assessing Corneal Nerve Functions in Patients With Ocular Surface Diseases
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
May 16, 2023 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
Dompé Farmaceutici S.p.A
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is designed to learn more about the impact different types of stimuli, such as heat, cold and vibration, can have on ocular pain response. This is called quantitative sensory testing (QST). Most procedures being performed in this study, except the QST, are standard of care which means they are performed during the participant's routine eye examination.
Detailed Description
Quantitative Sensory Test (QST) is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli for the purpose of characterizing somatosensory function or dysfunction.
In this study, we propose to evaluate corneal nerve functions in patients with corneal nerve abnormalities by QST and correlate the nerve functions with symptoms, clinical signs and nerve morphology detected by In-Vivo Confocal Microscopy (IVCM). Identification of corneal nerve functions and correlations with other findings may help us to understand underlying pathological mechanisms of the disease and may guide us toward new treatment targets.
We hypothesize that, QST may provide us detailed information about corneal nerve function alterations and may correlate with morphological nerve changes detected by IVCM.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Disease, Neuropathy, Dry Eye Disease, Neurotrophic Keratitis
Keywords
Quantitative Sensory Test
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
108 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Stage I Neurotrophic Keratopathy
Arm Type
Experimental
Arm Description
Clinical findings of corneal hyperplasia and irregularity, scattered small facets of dried epithelium, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.
Arm Title
Stage II Neurotrophic Keratopathy
Arm Type
Experimental
Arm Description
Clinical findings of corneal epithelial defect with smooth and rolled edges, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.
Arm Title
Dry Eye Disease
Arm Type
Experimental
Arm Description
Symptoms of dry eye disease for at least 3 months, supported by clinical finding of decreased tear film break-up time or ocular surface staining. Normal corneal sensation.
Arm Title
Healthy Individuals
Arm Type
Experimental
Arm Description
Absence of any ocular symptoms, absence of surface findings (including corneal or conjunctival staining, corneal scar or surgical wound), and normal corneal sensation.
Intervention Type
Device
Intervention Name(s)
Quantitative Sensory Test
Intervention Description
Quantitative Sensory Test (Medoc Ltd, Israel), QST is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli (modalities including heat, cold and vibration) for the purpose of characterizing somatosensory function or dysfunction. For this test, subjects will be seated comfortably on a chair in a quiet room, or laying supine in a horizontal examination chair, with ambient temperature of 24-25◦ C. Medial upper eyelid; just below the supraorbital notch, nasolacrimal sac area; 4-5 mm medial to nasal cantus, and non-dominant forearm will be used as test sites. Patients will be instructed in detail of the nature of the test and the need to react attentively and promptly to change in temperatures.
Primary Outcome Measure Information:
Title
Thermal stimulus response to QST on site of trigeminal nerve first branch, as assessed by cold detection threshold (CDT) and hot detection threshold (HDT)
Description
Cold and heat sensation thresholds will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken for each stimuli. Participants will receive successive ramps of gradually decreasing or increasing temperature, starting from a resting neutral temperature of 32°C. Participants will be instructed to press a response button when a thermal sensation (either cold or warm) is perceived.
Time Frame
From visit 1 up to 4 weeks
Title
Mechanical stimulus response to QST on site of trigeminal nerve first branch, as assessed by vibration detection threshold (VDT)
Description
Vibration sensation threshold will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken. Participants will receive successive ramps of gradually decreasing or increasing vibration, starting from. Participants will be instructed to press a response button when a mechanical sensation is perceived.
Time Frame
From visit 1 up to 4 weeks
Title
Differences in thermal stimulus pain threshold across the 4 study arms
Description
Cold pain threshold (CPT) and heat pain threshold (HPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from probe on QST testing
Time Frame
From visit 1 up to 4 weeks
Title
Differences in mechanical stimulus pain threshold across the 4 study arms
Description
Vibration pain threshold (VPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from vibration probe on QST testing
Time Frame
From visit 1 up to 4 weeks
Secondary Outcome Measure Information:
Title
To correlate the QST responses with morphological changes of corneal nerves detected by IVCM
Description
In vivo confocal microscopy (IVCM) imaging will be performed to observe for any morphological nerve changes; such as decreased nerve density, nerve tortuosity presence of microneuromas.
Time Frame
From visit 1 up to 4 weeks
Title
To correlate symptom severity as assessed by the Ocular Surface Disease Index (OSDI), to stimulus response across the 4 interventional arms.
Description
Ocular Surface Disease Index (OSDI) questionnaire A 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. The 12 items of the OSDI questionnaire are graded on a scale of 0 to 4, where 0 indicates none of the time; 1, some of the time; 2, half of the time; 3, most of the time; and 4, all of the time. The total OSDI score is then calculated on the basis of the following formula: OSDI= [(sum of scores for all questions answered) x 100]/[(total number of questions answered) x 4]. Higher OSDI scores represent greater severity of symptoms.
Time Frame
From visit 1 up to 4 weeks
Title
To compare QST response differences between trigeminal nerve first branch and forearm in patients.
Description
Measurement of stimuli detection thresholds, pain thresholds and pain ranges for different stimuli (cold, heat and vibration) type in study groups at 3 different periocular sites (just below supraorbital notch, lateral canthus, inferior orbital bone; 1 cm lateral of medial canthus) and non-dominant hand hypothenar eminence (as a reference site)
Time Frame
From visit 1 up to 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Group 1: Stage I Neurotrophic Keratopathy (NK)
Clinical findings of Stage I NK
Decreased nerve density by IVCM
Decreased corneal sensation
Group 2: Stage II NK
Clinical findings of Stage II NK
Decreased nerve density by IVCM
Decreased corneal sensation
Group 3: Dry Eye Disease (DED)
Symptoms of DED at least 3 months
Presence of at least one of the following DED signs; tear film break-up time lower than 7, ocular surface staining more than +1 based on NIH scale
Normal or mildly effected corneal sensation
Group 4: Healthy Individuals
Absence of any ocular surface symptoms
Absence of ocular surface findings
Transparent and clear cornea
Normal corneal sensation
Group 5: NCP
Presence of neuropathic symptoms AND
Symptoms out of proportion to clinical findings AND
Nerve abnormalities detected by in vivo confocal microscopy
Exclusion Criteria:
History of diabetes
History of ocular surgery, corneal infection, or corneal injury within the last 3 months
Systemic regular anti-inflammatory and/or steroid and/or immune-modulatory therapy in the last 3 months
Active ocular allergies
Any major psychiatric illness including bipolar, psychosis, obsessive-compulsive disorder and major depression
Pregnancy
History of surgery within the last 3 months
History of , sarcoidosis, GVHD or collagen vascular disease
Allergic to benzalkonium chloride "BAK" (an eye-drop preservative)
Concurrent enrollment in other studies that in the opinion of the investigator will interfere with the results of this study
Non-English speakers
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedram Hamrah, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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QST for Corneal Nerve Function
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