Dry Eye DiseasePhase 2NCT03660475
Effect of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic Subjects
A Phase 2 study testing Naltrexone in people with Dry Eye Disease, run by Sassani, Joseph S., MD, MHA at 1 site in United States.
Trial summary
The objective of this exploratory study is to determine the safety and efficacy of 0.002% Naltrexone Ophthalmic Solution, compared to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dry Eye Disease
- What is being tested?
- Naltrexone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2018to 15 Nov 2018
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written informed consent;
- Have a diagnosis of type 1 or type 2 diabetes mellitus prior to Visit 1;
- Have a reported history of dry eye for at least 6 months prior to Visit 1;
- Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
- Have a corneal fluorescein staining score of ≥ 2 in any region (inferior, superior, or central regions) in at least one eye at Visits 1 and 2 (must be the same eye at Visits 1 and 2);
- Have at least one of the following at Visits 1 and 2:
- A total lissamine green conjunctival score of ≥ 2 in at least one eye, based on the sum of the temporal and nasal regions at Visits 1 and 2 (must be the same eye at Visits 1 and 2);
- Report an OSDI score ≥ 20 at Visits 1 and 2.
Who cannot join
- Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters;
- Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
- Have concurrent neurotrophic keratopathy from a source other than diabetes (h/o HSV keratitis, h/o HZO with ocular manifestations, or CN VII palsy or other condition resulting in lagophthalmos);
- Have active diabetic foot ulcers;
- Have a corneal sensitivity score ≤ 1.5 cm as measured by Cochet-Bonnet at Visit 1;
- Report an OSDI score > 75 at Visits 1 and 2;
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- Have worn contact lenses within 21 days of Visit 1 or anticipate using contact lenses during the study (no contact lens wear during study);
- Have used any eye drops within 2 hours of Visit 1;
- Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 24 months;
- Have used cyclosporine 0.05% or lifitigrast 5.0% ophthalmic solution within 45 days of Visit 1;
- Have any planned ocular and/or lid surgeries over the study period or any ocular surgery within the last 12 months;
- Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;
- Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter (OTC) solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study);
- Have corrected visual acuity greater than or equal to logMAR +0.7 as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in either eye at Visit 1;
- Have concurrent autoimmune disease causing dry eye (e.g., rheumatoid arthritis, Sjogren's, GVHD, Steven's Johnson, Grave's);
- Have Fuchs endothelial dystrophy;
- Have recurrent corneal erosion syndrome or anterior basement membrane dystrophy;
- Be a woman who is pregnant, nursing, or planning a pregnancy;
- Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 5 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (i.e., has had a hysterectomy or bilateral tubal ligation), or is post-menopausal (without menses for 12 consecutive months);
- Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; IUD; or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, they must agree to use adequate birth control as defined above for the remainder of the study;
- Have a known allergy and/or sensitivity to the test article or its components;
- Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study;
- Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1;
- Be currently using any medication known to cause ocular drying that is not used on a stable dosing regimen for at least 30 days prior to Visit 1;
- Be unable or unwilling to follow instructions, including participation in all study assessments and visits.
- Be currently using a systemic opioid antagonist (e.g., Naltrexone or Naloxone) or have used a systemic opioid antagonist in the previous 90 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic Subjects
The objective of this exploratory study is to determine the safety and efficacy of 0.002% Naltrexone Ophthalmic Solution, compared to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects.
Read the detailed description
This is a Phase 2, single-center, double-masked, randomized, placebo-controlled study to compare the safety and efficacy of Naltrexone Ophthalmic Solution, 0.002% to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects. Subjects eligible to be randomized will receive one of the following treatments to be administered bilaterally BID for 29 days (from Visit 2 to Visit 5): Naltrexone Ophthalmic Solution, 0.002% or Placebo Ophthalmic Solution (Vehicle). During a 10-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Placebo Ophthalmic Solution (Vehicle) bilaterally BID. Participants who terminate early during the application period will be asked to complete safety assessments (if the participants agree) prior to study exit. Participants who are terminated early from the study will not be replaced.
- Conditions
- Dry Eye Disease
- Being tested
- Naltrexone, Placebos
- Keywords
- naltrexone, dry eye, diabetic subjects
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
naltrexone formulated as ophthalmic solution
PlacebosDrug
Placebo ophthalmic solution
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone | Experimental | Naltrexone Ophthalmic Solution 0.002% Receives: Drug: Naltrexone |
| Placebo | Placebo comparator | Placebo Ophthalmic Solution Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Ocular Surface Disease Index
The OSDI is 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. It is a scale of 0-4 for each of the 12 questions. A minimum value would be "0" and a maximum value would be "48". The higher the value the worse the outcome.
Measured: Day 29
Secondary outcomes (12)
Lissamine Green Staining
Lissamine green staining; regions: inferior, superior, central, corneal sum, temporal, nasal, conjunctival sum, total eye will be measured using an ocular discomfort score on a scale of 0 (no staining) to 4 (confluent staining). The total eye score is presented. A minimum score would be "0" and a maximal score would be "8". The higher the value the worse the outcome.
Measured: Day 29
Tear Film Break-up Time
Tear film break-up time is the time taken for the first dry spot to appear on the cornea after a complete blink.
Measured: Day 29
Conjunctival Redness
Conjunctival redness will be assessed and conjunctival pain will be assessed using a visual analog scale ranging from "0" (none: normal without vasodilation) to "5" (severe: broad ciliary and prominent, horizontal conjunctival vasodilation). A minimal score would be "0" and a maximal score would be "10". The higher the value the worse the outcome .
Measured: Day 29
Schirmer's Test
Schirmer's Test (without anesthesia) ) involves placing a Schirmer test strip in the lower temporal lid margin of each eye such that the strip fits tightly. Subjects will be instructed to close their eyes. After 5 minutes have elapsed, the Schirmer strip will be removed. The length of the moistened area will be recorded (mm) for each eye. A normal reading is ≥10 mm wetting of the paper after 5 minutes. Tear deficiency is <5 mm wetting of the paper after 5 minutes.
Measured: Day 29
Cochet-Bonnet Corneal Sensitivity Test
After extending the Cochet-Bonnet corneal sensitivity device (containing a thin, retractable, nylon monofilament) up to 6 cm in length and pressing against the cornea, the monofilament is slowly retracted incrementally in 0.5 cm steps until the patient can feel its contact and the length is recorded. The greater the length indicates increased sensation and the shorter the length indicates decreased sensation.
Measured: Day 29
Tear Osmolarity
Normal tear osmolarity is defined as < 300 mOsm/L in both eyes and an inter-eye difference of < 8 mOsm/L. Values greater than 300 mOsm/L are suggestive of dry eye.
Measured: Day 29
Matrix Metalloprotienase-9 (MMP-9) is a Marker of Inflammation.
Levels of MMP-9 will be measured in each eye using InflammaDry at Visit 5. The test will be recorded as either positive or negative. Dry eye patients generally exhibit positive levels of MMP-9., so the number of subjects testing positive for MMP-9 at Day 29 will be recorded.
Measured: Day 29
Ocular Discomfort (Scale 1)
Ocular discomfort scores will be subjectively graded by the subjects according to the following scale, rating each eye separately on a scale from 0-4. A score of "0" represents no discomfort and a score of "4" represents constant discomfort. A minimum score would be "0" and a maximum score would be "8". The higher the value the worse the outcome.
Measured: Day 29
Ocular Discomfort (Scale 2)
Subjects will rate the severity of each of the following symptoms, with regard to how both their eyes feel: overall ocular discomfort, burning, dryness, grittiness and stinging according to the following 6-point (0 to 5) scale where 0 = none and 5 = worst. A minimum score would be "0" and a maximum score would be "10". The higher the value the worse the outcome.
Measured: Day 29
Visual Analog Scale for Pain
Standard scale assessing a patient's level of pain on a scale of 0-100. The subject will be asked to rate each ocular symptom due to ocular dryness by placing a vertical mark on the horizontal line to indicate the level of discomfort. 0% corresponds to "no discomfort" and 100% corresponds to "maximal discomfort". The following parameters will be assessed: burning/stinging, itching, foreign body sensation, blurred vision, eye dryness, photophobia, and pain, with a total score for each eye reported. A minimal score would be "0" and a maximum score would be "200". The higher the value the worse the outcome.
Measured: Day 29
Fluorescein Staining
The following regions of each eye will be assessed for fluorescein staining: inferior, superior, central, corneal sum, temporal, nasal, conjunctival sum, and a total eye score recorded. A score of "0" represents no staining and a score of "4" represents confluent staining. A minimum score would be "0" and a maximum score would be "8". A higher values represent a worse outcome.
Measured: Day 29
Visual Acuity Measured by Assessing Average Change in LogMAR Units for Both Eyes at Day 29. LogMAR Units Range From 0-1.0, With the Higher the Number Indicating a Worsening in Vision.
Mean change in visual acuity (LogMAR units 0-1.0) for both eyes at Day 29 was determined for each treatment arm and considered a measure of safety.
Measured: Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2018
- Study start31 Jul 2018
- Primary completion1 Nov 2018
- Study completion15 Nov 2018
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 Dry Eye DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sassani, Joseph S., MD, MHA
- Responsible party
- Sponsor
- Investigators
- Eugene B McLaurin, M.D., Principal investigator, Total Eye Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03660475
- Sponsor's protocol ID
- DDES001/18-110-0002
- Status last verified
- Oct 2022
- First submitted
- 18 Jul 2018
- Last updated
- 2 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic Subjects
- ClinicalTrials.gov ID
- NCT03660475
- Acronym / sponsor ID
- DDES001/18-110-0002
- Conditions
- Dry Eye Disease
- Keywords
- naltrexone, dry eye, diabetic subjects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Sassani, Joseph S., MD, MHA
- Study start
- 31 Jul 2018 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 15 Nov 2018 (actual)
- First posted
- 6 Sep 2018 (actual)
- Results
- Posted 2 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this exploratory study is to determine the safety and efficacy of 0.002% Naltrexone Ophthalmic Solution, compared to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects.
Detailed description
This is a Phase 2, single-center, double-masked, randomized, placebo-controlled study to compare the safety and efficacy of Naltrexone Ophthalmic Solution, 0.002% to placebo for the treatment of the signs and symptoms of dry eye in diabetic subjects. Subjects eligible to be randomized will receive one of the following treatments to be administered bilaterally BID for 29 days (from Visit 2 to Visit 5): Naltrexone Ophthalmic Solution, 0.002% or Placebo Ophthalmic Solution (Vehicle). During a 10-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Placebo Ophthalmic Solution (Vehicle) bilaterally BID. Participants who terminate early during the application period will be asked to complete safety assessments (if the participants agree) prior to study exit. Participants who are terminated early from the study will not be replaced.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naltrexone | Experimental | Drug: NaltrexoneNaltrexone Ophthalmic Solution 0.002% |
| Placebo | Placebo comparator | Drug: PlacebosPlacebo Ophthalmic Solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Provide written informed consent;
- Have a diagnosis of type 1 or type 2 diabetes mellitus prior to Visit 1;
- Have a reported history of dry eye for at least 6 months prior to Visit 1;
- Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
- Have a corneal fluorescein staining score of ≥ 2 in any region (inferior, superior, or central regions) in at least one eye at Visits 1 and 2 (must be the same eye at Visits 1 and 2);
Key exclusion criteria (26 listed)
- Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters;
- Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
- Have concurrent neurotrophic keratopathy from a source other than diabetes (h/o HSV keratitis, h/o HZO with ocular manifestations, or CN VII palsy or other condition resulting in lagophthalmos);
- Have active diabetic foot ulcers;
- Have a corneal sensitivity score ≤ 1.5 cm as measured by Cochet-Bonnet at Visit 1;
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 |
|---|---|---|
| Naltrexonenaltrexone formulated as ophthalmic solution | Drug | Naltrexone |
| PlacebosPlacebo ophthalmic solution | Drug | Placebo |
Primary outcome
Total Ocular Surface Disease Index
Time frame: Day 29
The OSDI is 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. It is a scale of 0-4 for each of the 12 questions. A minimum value would be "0" and a maximum value would be "48". The higher the value the worse the outcome.
12 secondary outcomes
Lissamine Green Staining
Time frame: Day 29
Tear Film Break-up Time
Time frame: Day 29
Conjunctival Redness
Time frame: Day 29
Schirmer's Test
Time frame: Day 29
Cochet-Bonnet Corneal Sensitivity Test
Time frame: Day 29
Tear Osmolarity
Time frame: Day 29
Matrix Metalloprotienase-9 (MMP-9) is a Marker of Inflammation.
Time frame: Day 29
Ocular Discomfort (Scale 1)
Time frame: Day 29
Ocular Discomfort (Scale 2)
Time frame: Day 29
Visual Analog Scale for Pain
Time frame: Day 29
Fluorescein Staining
Time frame: Day 29
Visual Acuity Measured by Assessing Average Change in LogMAR Units for Both Eyes at Day 29. LogMAR Units Range From 0-1.0, With the Higher the Number Indicating a Worsening in Vision.
Time frame: Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Eugene B McLaurin, M.D. principal investigator
Total Eye Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone in people with Dry Eye Disease, run by Sassani, Joseph S., MD, MHA 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 8 inclusion and 26 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: finished, as of the sponsor's last update on 2 Dec 2022. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2022). 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?
Total Ocular Surface Disease Index (time frame: Day 29). 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 2 Dec 2022.