Dry Eye, Graft vs. Host Disease, Sjogren's Syndrome
Conditions
Keywords
Dry Eye, Sjogren's Syndrome, Graft vs. Host Disease, Rheumatoid arthritis, Systemic lupus erythematosus, Scleroderma
Brief summary
Severe dry eye is a debilitating ocular disease resulting in loss of vision, reduced day-to-day function and significant discomfort. Tear substitutes are an important part of the treatment of all patients, however, even with aggressive us, the corneal(ocular)surface often remains very irregular due to poor surface healing. The agent being evaluated in this study, Thymosin Beta 4, promotes healing of the corneal surface and has been studied in patients with recalcitrant corneal ulcers and erosions with significant success (Arch Ophthalmol. 2010;128(5):636-638., Ann of the NY Acad of Sci, May, 2010). The study hypothesis is that Thymosin Beta 4, in its role as a modulator of corneal surface healing, may be able to promote healing of the corneal surface allowing for more conventional modalities to take over and maintain a smooth and regular ocular surface. The investigators hope to be able to demonstrate an improvement in visual acuity, surface healing and a reduction in dry-eye related symptoms.
Detailed description
See above
Interventions
DRUGThymosin Beta 4 eye drops
Patients will be randomized and will receive the same eye drops the Thymosin Beta 4.
DRUGVehicle Control
Patients will be randomized and will receive the same eye drops without the Thymosin Beta 4.
Sponsors
Kresge Eye Institute
Michigan Cornea Consultants, PC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Schirmers of \< 5 mm at 5 minutes * TFBUT: less than 10 seconds * Corneal staining of \>3 of 15: conjunctival staining of \>3 of 18 * Ocular Surface Disease Index of \> 50 * Presumed best corrected vision of 20/60 or better
Exclusion criteria
* Acute or inflammatory corneal disease * Pregnancy or lactation * Monocular status * Punctal occlusion within 30 days * Ocular surgery within 3 months * Corneal thinning of \>50% * Active corneal infection * History of ocular malignancy * Retinal neovascularization * Current use of topical cyclosporin A
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | Day 1, Day 14, Day 28 and Day 56 | Sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56. Measurable by Intra-ocular pressure (IOP) by applanation tonometry, Complete ophthalmologic evaluation including fundoscopy, An adverse event (baseline and all subsequent study visits). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corneal Fluorescein Staining | Days 56 (+28 day follow up) | Ocular surface irregularity as measured by Slit Lamp Examination (SLE) with fluorescein dye staining of the cornea at days 56 (+28 day follow up). The scale used to determine the difference in corneal fluorescein staining is the Oxford scale. (The Oxford Scale measures corneal fluorescein staining) Corneal staining type was assessed by the investigator for each of 5 regions of the cornea, i.e., four quadrants plus central. The five regions were summed, for a maximum score of 25. A higher score represents greater disability. |
| Ocular Discomfort Index | Days 56 (+28 day follow up) | Dry eye causes ocular discomfort, which is measured using a Ocular Surface Disease Index at 56 day (+28 day followup). (Symptomatic improvement using the validated Ocular Surface Disease Index (OSDI). The OSDI is a questionnaire that consists of 12 questions about ocular irritation and the effect of dry eye on vision. For every question, participants check a score between 0 and 4, where 0 equals none of the time and 4 equals all of the time. OSDI scores are calculated according to: OSDI = \[(sum of scores for all questions answered)\*100\] / \[(total number of questions answered)\*4\]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. |
| Tear Film Break up Time | Days 56 (+28 day follow up) | Tear film break up time (TFBUT) was measured to evaluating the quality of tear at 56 day (+28 day follow up). The tear film break-up time is defined as the interval between the last complete blink and the first appearance of a dry spot, or disruption in the tear film. Range : \>10 seconds is thought to be normal, \<5 seconds low (with high likelihood of dry eye symptoms). |
Countries
United States
Participant flow
Recruitment details
Recruitment Details The study took place at Kresge Eye Institute by Dr. Gabriel Sosne, and at Michigan Cornea Consultants, P.C. by Dr. Steven P. Dunn, The first subject was screened on Mar.2011 and the last subject last visit to the clinic was on Dec.2012
Pre-assignment details
Pre-assignment Details: Subjects were evaluated upon entering the study after a two week washout period.
Participants by arm
| Arm | Count |
|---|---|
| Thymosin Comparison
Thymosin Beta 4 eye drops vs. vehicle: Patients will be randomized and will receive either Thymosin Beta 4 eye drops or the same eye drops without the Thymosin Beta 4. | 6 |
| Placebo Comparison
Thymosin Beta 4 eye drops vs. vehicle: Patients will be randomized and will receive either Thymosin Beta 4 eye drops or the same eye drops without the Thymosin Beta 4. | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | Placebo | Thymosin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 7 Participants |
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 6.65 | 54.2 Years STANDARD_DEVIATION 11.6 | 57.33 Years STANDARD_DEVIATION 11.18 |
| Region of Enrollment United States | 3 participants | 6 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 |
Outcome results
Primary
Safety
Sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56. Measurable by Intra-ocular pressure (IOP) by applanation tonometry, Complete ophthalmologic evaluation including fundoscopy, An adverse event (baseline and all subsequent study visits).
Time frame: Day 1, Day 14, Day 28 and Day 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymosin | Safety | 0 event |
| Placebo | Safety | 0 event |
Secondary
Corneal Fluorescein Staining
Ocular surface irregularity as measured by Slit Lamp Examination (SLE) with fluorescein dye staining of the cornea at days 56 (+28 day follow up). The scale used to determine the difference in corneal fluorescein staining is the Oxford scale. (The Oxford Scale measures corneal fluorescein staining) Corneal staining type was assessed by the investigator for each of 5 regions of the cornea, i.e., four quadrants plus central. The five regions were summed, for a maximum score of 25. A higher score represents greater disability.
Time frame: Days 56 (+28 day follow up)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thymosin | Corneal Fluorescein Staining | 4.5 units on a scale | Standard Deviation 3.406 |
| Placebo | Corneal Fluorescein Staining | 11.0 units on a scale | Standard Deviation 4.927 |
Comparison: Comparison of fluorescein staining score between the placebo and Thymosin beta 4 groupsp-value: 0.0108t-test, 2 sided
Secondary
Ocular Discomfort Index
Dry eye causes ocular discomfort, which is measured using a Ocular Surface Disease Index at 56 day (+28 day followup). (Symptomatic improvement using the validated Ocular Surface Disease Index (OSDI). The OSDI is a questionnaire that consists of 12 questions about ocular irritation and the effect of dry eye on vision. For every question, participants check a score between 0 and 4, where 0 equals none of the time and 4 equals all of the time. OSDI scores are calculated according to: OSDI = \[(sum of scores for all questions answered)\*100\] / \[(total number of questions answered)\*4\]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability.
Time frame: Days 56 (+28 day follow up)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thymosin | Ocular Discomfort Index | 45.625 units on a scale | Standard Deviation 17.78 |
| Placebo | Ocular Discomfort Index | 67.233 units on a scale | Standard Deviation 15.658 |
Comparison: Comparison of Ocular Discomfort Index score between the placebo and Thymosin beta 4 groupsp-value: 0.0141t-test, 2 sided
Secondary
Tear Film Break up Time
Tear film break up time (TFBUT) was measured to evaluating the quality of tear at 56 day (+28 day follow up). The tear film break-up time is defined as the interval between the last complete blink and the first appearance of a dry spot, or disruption in the tear film. Range : \>10 seconds is thought to be normal, \<5 seconds low (with high likelihood of dry eye symptoms).
Time frame: Days 56 (+28 day follow up)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thymosin | Tear Film Break up Time | 5.550 seconds | Standard Deviation 2.302 |
| Placebo | Tear Film Break up Time | 2.848 seconds | Standard Deviation 1.137 |
Comparison: Comparison of Tear Film Break up Time between the placebo and Thymosin beta 4 groups.p-value: 0.0162t-test, 2 sided