Dry Eye
Conditions
Keywords
Nutraceutical supplement
Brief summary
The aim of this study is to compare ocular symptoms and signs when the test nutraceutical formulation (combination of flaxseed oil, borage oil and fish oil omega-3 fatty acids) is consumed daily over a 3 month period, with a control capsule that contains polyethylene glycol (PEG), oleic acid and propylene glycol, which are found in many pharmaceutical products and are generally considered to be biologically inert and safe. There is good evidence that the consumption of oily fish has a protective effect against dry eye, and other studies have provided evidence of the beneficial effect of supplementation with omega-3 essential fatty acids in the treatment of dry eye disease. However, there have been limited well designed clinical trials investigating the potential for nutraceutical dietary supplementation to impact ocular comfort. To date, no controlled, randomised clinical trials have been conducted to evaluate the test nutraceutical formulation. Therefore, the purpose of this study is to conduct a randomized, placebo-controlled, double-masked study to investigate the effects of dietary supplementation with a combination of flaxseed oil, borage oil and fish oil omega-3 fatty acids on ocular comfort including signs and symptoms of dry eye.
Detailed description
This study will be a prospective, randomised, placebo-controlled, double masked study conducted over a 3-month period. One hundred and thirty-eight (138) participants who meet the inclusion / exclusion criteria and give informed consent will be randomised to either the test capsules containing a combination of flaxseed oil, borage oil and fish oil omega-3 fatty acids or placebo capsules, identical in appearance, containing polyethylene glycol, oleic acid and propylene glycol (found in many pharmaceutical products and considered to be biologically inert and safe) to be taken by mouth three times daily for 40 days, and then twice daily thereafter for approximately 50 days. Every effort will be made to stratify enrolment by disease severity to ensure participants with mild, moderate and severe dry eye are represented in the study population. Stratification will be in a 2:2:1 fashion i.e. OSDI score \>12 (55 participants), OSDI score \>20 (55 participants) and OSDI score \>45 (28 participants). Participants will be stratified according to dry eye severity prior to randomisation. There will be a total of 3 scheduled study visits over a period of approximately 3 months - Day 1, 1 month and 3 months. Ocular comfort and symptoms of dry eye will be assessed via questionnaires. The tear film and ocular surface will be assessed using specialised instruments including the slit lamp biomicroscope, Lipiview Ocular Surface Interferometer, Vapometer and Oculus Keratograph 5M, and stains. Safety will be assessed through measurement of vision, ocular redness and evaluation of the ocular surface using the slit lamp biomicroscope. Those participants who meet the eligibility criteria will be randomly allocated to either the test or control capsules. An adequate supply of capsules will be dispensed to last until the next Participants will be instructed to ingest one capsule three times daily with meals for 40 days, and then two times daily until their final 3 month study visit.
Interventions
DIETARY_SUPPLEMENTSupplement
Concentrated Omega-3 Triglycerides-fish 332 mg Equiv. Eicosapentaenoic Acid (EPA) 134 mg Equiv. Docosahexaenoic Acid (DHA) 66.8 mg Flax Seed Oil (Linseed Oil) 334 mg Equiv. Oleic acid 58.5 mg Equiv. Linoleic acid 58.5 mg Equiv. Linolenic acid 192 mg Borago officinalis seed oil fixed (Borage) 434 mg Equiv. gamma-Linolenic acid 95.5 mg
DIETARY_SUPPLEMENTPlacebo
polyethylene glycol (500mg), oleic acid (659mg) and propylene glycol (115mg)
Sponsors
The University of New South Wales
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double masked
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Able to read and comprehend English and give informed consent as demonstrated by signing a record of informed consent; * Be at least 18 years old; * Have symptoms of ocular discomfort as measured with the Ocular Surface Disease Index (OSDI) score of \>12 at the Baseline visit; * Willing to comply with the dosage and study visit schedule as directed by the investigator; * No contact lens wear in the last 30 days and willing to refrain from contact lens wear for the duration of the study; * No planned changes to diet and willing not to substantially alter their usual diet for the duration of the study, including their typical intake of fish; * Willingness to notify the study investigator if instructed to alter their diet by health/medical practitioner; * Willing to continue using any artificial tear supplements at the same frequency throughout the study, as used prior to the study * Have health and ocular health findings which would not prevent the participant from safely ingesting dietary supplementation with combination omega oils
Exclusion criteria
* Any systemic disease that would preclude participants from safely ingesting dietary supplementation with combination omega oils; * Self-reported allergy/sensitivity to any of the study product ingredients; * Use of any polyunsaturated fatty acid-containing dietary supplements (such as fish oil, evening primrose oil, linseed oil) up to 12 weeks prior to the start of the study; * Use of any of the following medications (including steroids) up to 12 weeks prior to start of the study or during the course of the study: * Ocular medication, category S3 and above; * Any systemic or topical medications that will affect ocular physiology e.g. anti-acne medications such as Roaccutane and corticosteroid or immunosuppressant medications such as Hydrocortisone, Prednisolone and antihistamine medications such as Claritine; * Any systemic disease that may affect ocular health e.g. Graves disease, and auto-immune diseases such as ankolysing spondylitis, multiple sclerosis and systemic lupus erythematosis; * Epilepsy or history of migraines exacerbated by flashing, strobe-like lights; * Eye surgery within 6 months immediately prior to enrolment for this study; * Rigid or soft contact lens wearer, including orthokeratology in the last 30 days; * Previous corneal refractive surgery; * Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Ocular Symptoms | 3 months | Measured using the Ocular Surface Disease Index questionnaire. Ocular surface disease index is assessed on a scale of 0 to 100 with higher score representing greater disability. Scores can range from 10 to 100. |
| Subjective Ocular Comfort | 3 months | Measured using the Ocular Comfort Index questionnaire. Ocular comfort index questionnaire score range from 0 to 72. Lowest slow indicates better subjective symptoms. |
| Subjective Ocular Dryness | 3 months | Measured using the Dry Eye Questionnaire 5. Dry eye questionnaire 5 score ranges from 0 to 22. Lower score represents better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tear Volume | 3 months | Measured in millimeters using phenol red thread tests |
| Non-invasive Tear Film Break-up Time | 3 months | Measured in seconds using the Oculus Keratograph. Higher value represents better outcome. |
| Tear Film Lipid Layer Thickness | 3 months | Measured in nanometers using the LipiView ocular surface interferometer |
| Tear Evaporation Rate | 3 months | Measured in g.m\^2.h using the Vapometer |
| Tear Meniscus Height | 3 months | Measured in millimeters using the Oculus Keratograph 5M |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Supplement Combination of flaxseed oil, borage oil and fish oil omega-3 fatty acids
Lacritec: Concentrated Omega-3 Triglycerides-fish 332 mg Equiv. Eicosapentaenoic Acid (EPA) 134 mg Equiv. Docosahexaenoic Acid (DHA) 66.8 mg Flax Seed Oil (Linseed Oil) 334 mg Equiv. Oleic acid 58.5 mg Equiv. Linoleic acid 58.5 mg Equiv. Linolenic acid 192 mg Borago officinalis seed oil fixed (Borage) 434 mg Equiv. gamma-Linolenic acid 95.5 mg | 61 |
| Placebo Polyethylene glycol, Oleic acid, Propylene glycol
Placebo: polyethylene glycol (500mg), oleic acid (659mg) and propylene glycol (115mg) | 58 |
| Total | 119 |
Baseline characteristics
| Characteristic | Supplement | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 4 Participants | 2 Participants |
| Age, Categorical >=65 years | 10 Participants | 24 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 91 Participants | 42 Participants |
| Age, Continuous | 38.9 years STANDARD_DEVIATION 18.2 | 41.43 years STANDARD_DEVIATION 18.83 | 44.1 years STANDARD_DEVIATION 19.2 |
| Dry Eye Questionnaire - 5 | 12.43 units on a scale | 11.80 units on a scale | 11.5 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 119 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Non-invasive tear break-up time | 11.7 seconds STANDARD_DEVIATION 5.1 | 11.70 seconds STANDARD_DEVIATION 6.28 | 12.0 seconds STANDARD_DEVIATION 6.4 |
| Ocular Comfort Index | 40.6 units on a scale | 39.0 units on a scale | 38.9 units on a scale |
| Ocular Surface Disease Index | 37 units on a scale | 36 units on a scale | 36 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants | 60 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 59 Participants | 33 Participants |
| Region of Enrollment Australia | 61 Participants | 119 Participants | 58 Participants |
| Sex: Female, Male Female | 44 Participants | 81 Participants | 37 Participants |
| Sex: Female, Male Male | 17 Participants | 38 Participants | 21 Participants |
| Tear Evaporation | 58.03 g.m^2.h | 58.24 g.m^2.h | 58.36 g.m^2.h |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 58 |
| other Total, other adverse events | 13 / 61 | 15 / 58 |
| serious Total, serious adverse events | 0 / 61 | 0 / 58 |
Outcome results
Primary
Subjective Ocular Comfort
Measured using the Ocular Comfort Index questionnaire. Ocular comfort index questionnaire score range from 0 to 72. Lowest slow indicates better subjective symptoms.
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lacritec | Subjective Ocular Comfort | 35.61 score on a scale |
| Placebo | Subjective Ocular Comfort | 35.66 score on a scale |
Primary
Subjective Ocular Dryness
Measured using the Dry Eye Questionnaire 5. Dry eye questionnaire 5 score ranges from 0 to 22. Lower score represents better outcome.
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lacritec | Subjective Ocular Dryness | 9.75 score on a scale |
| Placebo | Subjective Ocular Dryness | 9.78 score on a scale |
Primary
Subjective Ocular Symptoms
Measured using the Ocular Surface Disease Index questionnaire. Ocular surface disease index is assessed on a scale of 0 to 100 with higher score representing greater disability. Scores can range from 10 to 100.
Time frame: 3 months
Population: All participant received at-least one dose of treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lacritec | Subjective Ocular Symptoms | 27.42 score on a scale |
| Placebo | Subjective Ocular Symptoms | 27.43 score on a scale |
Secondary
Non-invasive Tear Film Break-up Time
Measured in seconds using the Oculus Keratograph. Higher value represents better outcome.
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lacritec | Non-invasive Tear Film Break-up Time | 11.50 Seconds |
| Placebo | Non-invasive Tear Film Break-up Time | 11.49 Seconds |
Secondary
Tear Evaporation Rate
Measured in g.m\^2.h using the Vapometer
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacritec | Tear Evaporation Rate | 59.10 g.m^2.h | Standard Deviation 25.41 |
| Placebo | Tear Evaporation Rate | 59.11 g.m^2.h | Standard Deviation 25.48 |
Secondary
Tear Film Lipid Layer Thickness
Measured in nanometers using the LipiView ocular surface interferometer
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacritec | Tear Film Lipid Layer Thickness | 64.59 nm | Standard Deviation 20.33 |
| Placebo | Tear Film Lipid Layer Thickness | 64.84 nm | Standard Deviation 19.98 |
Secondary
Tear Meniscus Height
Measured in millimeters using the Oculus Keratograph 5M
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacritec | Tear Meniscus Height | 0.26 mm | Standard Deviation 0.1 |
| Placebo | Tear Meniscus Height | 0.27 mm | Standard Deviation 0.19 |
Secondary
Tear Volume
Measured in millimeters using phenol red thread tests
Time frame: 3 months
Population: All participants received at least one dose of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lacritec | Tear Volume | 18.17 mm | Standard Deviation 6.73 |
| Placebo | Tear Volume | 18.13 mm | Standard Deviation 6.89 |