DREAM: Dry Eye Assessment and Management: Feasibility Study

• Sponsor: Asbell, Penny, M.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01102257
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 13.9
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to test a protocol investigating the efficacy of omega-3 fatty acids in treating dry eye disease. The study is termed "feasibility" because its purpose is to demonstrate an ability to execute the proposed protocol with compliance at two sites rather than generate statistically relevant data concerning the safety and efficacy of the supplement in patients with dry eye disease.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes; Keratoconjunctivitis Sicca	Drug: Omega-3 EFA Supplement; Drug: Olive Oil	Phase 2/Phase 3

Detailed Description

Dry eye disease (DED) is a common but often inadequately treated disease of the tears and surface of the eye. It can cause poor vision and chronic pain and is more frequent with increasing age. Inflammation may be an important component of this disease. This is supported by the observation that cyclosporine, a drug that targets the immune system, is approved for and effectively treats DED. Inflammatory processes likely produce ocular surface damage and contribute to chronic DED. Because not all people with DED respond to current anti-inflammatory treatments, other immune-modulating treatments would be of value. Furthermore, despite a great deal of evidence supporting DED as an inflammatory disease, not all researchers currently agree with this classification. More data that specifically measures inflammatory responses in DED needs to be collected in a well-characterized patient population and correlated with signs and symptoms of DED in order to improve our understanding and classification of the disease.

Essential Fatty Acids (EFA) have been shown to diminish inflammatory responses in many human inflammatory diseases, and interest in the use of omega-3 and omega-6 fatty acids for disease treatment has resulted in several small studies as well as the use (and over-the-counter availability) of EFA-containing nutritional supplements, including several specifically for the treatment of DED. Despite this interest in EFA for DED, there are no strong empirical data from a well-controlled randomized controlled trial RCT supporting the use of EFA for DED. We postulate that DED is an inflammatory disease and hypothesize that EFA can mediate immune responses, thus improving DED signs, symptoms and associated measures of inflammation. The proposed three month feasibility study allows us the chance to demonstrate our ability to successfully execute our own protocol with compliance from the study patients before we begin the process of initiating a full-scale multi-center trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Trial of Essential Fatty Acids for Dry Eye Disease: Feasibility Study
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omega-3 EFA Supplement The total daily dose from the 5 capsules in treatment group will be 3.0 grams of omega-3 esssential fatty acid i.e Omega-3 EFA supplement comprised of: 2000 mg EPA 1000 mg DHA	Drug: Omega-3 EFA Supplement; The total daily dose from the 5 capsules in treatment group will be 3.0 grams of omega-3 EFAs comprised of: 2000 mg EPA 1000 mg DHA; Other Names: Fish oil supplements
Placebo Comparator: Olive Oil Gel Capsule	Drug: Olive Oil; Placebo group will take 5 capsules a day containing 3.0 grams of olive oil

Outcome Measures

Primary Outcome Measures

1. Change on Ocular Surface Disease Index (OSDI) [90 +/- 14 days following initiation of drug regimen]

2. Change in REd Blood Cell(RBC) Membrane Fatty Acid(FA) Content [Baseline and 3 Months]

Secondary Outcome Measures

1. Change on Brief Ocular Discomfort Inventory (BODI) [90 +/- 14 days following initiation of drug regimen]

2. Change on Impact of Dry Eye on Everyday Life (IDEEL) [90 +/- 14 days following initiation of drug regimen]

3. Change in Quality of Life Associated With Chronic Pain [90 +/- 14 days following initiation of drug regimen]

4. Change in the Ocular Surface [90 +/- 14 days following initiation of drug regimen]

5. Change in Schirmer's [90 +/- 14 days following initiation of drug regimen]

6. Change in Relevant Biomarkers: HLA-DR, MUC 5A, Cytokines [90 +/- 14 days following initiation of drug regimen]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Sign and date the informed consent form approved by the IRB.

2. ≥ 18 years of age

3. Demonstrate at least 2 of the 4 following signs in the same eye at two consecutive visits (Visit 1: 7 - 21 days prior to randomization, and Visit 2: day of randomization).

4. Conjunctival staining present ≥ 1

5. Corneal fluorescein staining present ≥ 1

6. Tear film break up time (TFBUT) ≤ 7 seconds

7. Schirmer test ≤ 7 mm/5min

8. Demonstrate symptoms of dry eye disease (OSDI score of at least 22 at screening visit and at least 15 at randomization visit).

9. Use or desire to use artificial tears on average of 2 times per day in the 2 weeks preceding study entry (run in period). No newly diagnosed patients can be enrolled and if a new patient wants to participate, she/he must be put on tears and re-evaluated in 6 months.

10. Intraocular pressure (IOP) ≥ 5 mmHg and ≤ 22 mmHg in each eye.

11. Women of child-bearing potential must agree to use a reliable method of contraception during study participation, and must demonstrate a negative urine pregnancy test at screening visit.

12. Be willing/able to return for all study visits and to follow instructions from the study investigator and his/her staff.

13. Be able to swallow large, soft gelcaps

Exclusion Criteria:

1. Patients who are allergic to ingredients of the active or placebo pills (fish, olive oil).

2. Current diagnosis of ocular infection (e.g. bacterial, viral or fungal).

3. History of ocular herpetic keratitis.

4. Eye surgery (including cataract surgery) within 6 months prior to randomization.

5. Previous LASIK surgery

6. Pregnant or nursing/lactating

7. Participation in a study of an investigational drug or device within the past 30 days.

8. Recent (≤ 3 months) initiation of use of systemic corticosteroids or other immunosuppressive agent and/or is planning to change treatment during study participation

9. Cognitive or psychiatric deficit that precludes informed consent or ability to perform requirements of the investigation.

10. Contact lens wearers

11. Use of glaucoma medication or history of surgery for glaucoma.

12. Recent (≤ 3 months) insertion of punctual plugs.

13. Using punctual plugs but unwilling to commit to their use for the duration of the study.

14. Unwilling to commit to same brand of artificial tears throughout the study.

15. Current use of EPA/DHA supplements in excess of 1 gram/day.

16. Recent (≤ 6 months) initiation of use of Restasis.

17. Use of Restasis but unwilling to commit to use of Restasis for the duration of the study.

18. Discontinued use of Restasis within the last 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai School of Medicine	New York	New York	United States	10029

Sponsors and Collaborators

• Asbell, Penny, M.D.
• National Eye Institute (NEI)

Investigators

• Principal Investigator: Penny Asbell, • MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Penny Asbell, Professor, Asbell, Penny, M.D.
• ClinicalTrials.gov Identifier: NCT01102257
• Other Study ID Numbers: 05-1099; 1R34EY017626
• First Posted: Apr 13, 2010
• Last Update Posted: Aug 23, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Penny Asbell, Professor, Asbell, Penny, M.D.: Dry Eye Disease; DED; Keratoconjunctivitis Sicca; Omega-3
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis

Study Results

Participant Flow

Arm/Group Title	Omega-3 Supplement	Olive Oil
Arm/Group Description	5 Gel Capsules to be taken orally daily to give a total dose of 2000mg EPA and 1000 mg DHA	5 Gel Capsules of olive oil to be taken orally daily
Period Title: Overall Study
STARTED	9	9
COMPLETED	7	9
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Omega-3 Supplement	Olive Oil	Total
Arm/Group Description	5 Gel Capsules taken orally to achieve a daily dose of 2000mg EPA and 1000mg DHA	5 Gel Capsules of olive oil taken orally daily	Total of all reporting groups
Overall Participants	9	9	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 66.7%	6 66.7%	12 66.7%
>=65 years	3 33.3%	3 33.3%	6 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (14)	57 (15)	56 (14)
Sex: Female, Male (Count of Participants)
Female	8 88.9%	7 77.8%	15 83.3%
Male	1 11.1%	2 22.2%	3 16.7%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	18 100%

Outcome Measures

1. Primary Outcome

Title	Change on Ocular Surface Disease Index (OSDI)
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	Change on Brief Ocular Discomfort Inventory (BODI)
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Change on Impact of Dry Eye on Everyday Life (IDEEL)
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change in Quality of Life Associated With Chronic Pain
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change in the Ocular Surface
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change in Schirmer's
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change in Relevant Biomarkers: HLA-DR, MUC 5A, Cytokines
Time Frame	90 +/- 14 days following initiation of drug regimen

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Primary Outcome

Title	Change in REd Blood Cell(RBC) Membrane Fatty Acid(FA) Content
Time Frame	Baseline and 3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omega-3 Supplement	Olive Oil
Arm/Group Description	5 Gel Capsules taken orally to achieve a daily dose of 2000mg EPA and 1000mg DHA	5 Gel Capsules of olive oil taken orally daily
Measure Participants	7	9
eicosapentaenoic acid(EPA)	1.46	0.05
docosahexaenoic acid(DHA)	1.49	0.25
Arachdinocic acid(AA)	-1.91	-0.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omega-3 Supplement, Olive Oil
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	Omega-3 Supplement		Olive Oil
Arm/Group Description	5 Gel Capsules taken orally to achieve a daily dose of 2000mg EPA and 1000mg DHA		5 Gel Capsules of olive oil taken orally daily
All Cause Mortality
	Omega-3 Supplement		Olive Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Omega-3 Supplement		Olive Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)		1/9 (11.1%)
Immune system disorders
Adnexal mass due to graft verus host disease	1/9 (11.1%)	1	0/9 (0%)	0
Nervous system disorders
Migraine	0/9 (0%)	0	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/9 (11.1%)	1	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Omega-3 Supplement		Olive Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		2/2 (100%)
Eye disorders
watery eyes	1/1 (100%)	1	1/1 (100%)	1
Nervous system disorders
thirst	1/1 (100%)	1	1/1 (100%)	1
nausea	2/2 (100%)	2	0/0 (NaN)	0

Limitations/Caveats

DREAM: Feasibility Study, is labeled "feasibility" because its primary end-point is to demonstrate an ability to execute the protocol rather than generate statistically relevant data on the safety and efficacy of omega-3 EFA in patients with DED.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.