Six Month Study to Evaluate the Safety and Effectiveness of the Intranasal Lacrimal Neurostimulator

• Sponsor: Oculeve, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02526290
• Collaborator: (none)
• Enrollment: 97
• Locations: 3
• Arm: 1
• Actual Duration (Months): 8
• Patients Per Site: 32.3
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

In this study, the safety and effectiveness of the Oculeve Intranasal Lacrimal Neurostimulator after 180 days of use in participants with aqueous tear deficiency will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes; Keratoconjunctivitis Sicca	Device: Intranasal Lacrimal Neurostimulator (Oculeve)	N/A

Detailed Description

This is a prospective, single-arm, multicenter, open-label clinical trial in which participants will use the Oculeve Intranasal Lacrimal Neurostimulator to stimulate tear production for 180 days. Participants will have a Screening Visit within 60 days prior to the initial device application. Device application will be initiated at Day 0, at which time participants will receive training on the proper use of the device. Participants will receive follow-up visits at Days 7, 30, 90 and 180.

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Single-Arm, Multicenter, Open-Label Study to Evaluate the Safety and Effectiveness of the Oculeve Intranasal Lacrimal Neurostimulator in Participants With Aqueous Tear Deficient Dry Eye
• Actual Study Start Date: Aug 31, 2015
• Actual Primary Completion Date: Apr 30, 2016
• Actual Study Completion Date: Apr 30, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active - Device The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration.	Device: Intranasal Lacrimal Neurostimulator (Oculeve); Neurostimulation device

Outcome Measures

Primary Outcome Measures

1. Stimulated Acute Tear Production [The stimulated and prestimulation (basal) measures were both performed at Day 180.]

   Stimulated acute tear production in the study eye at Day 180 as measured by the difference between the Schirmer test score during stimulation and the test score before stimulation (basal). The Schirmer strip is placed just under the eyelid and wicks up the tears. It measures tear production on a linear scale of 0-35 mm.

Secondary Outcome Measures

1. Corrected Distance Visual Acuity [Baseline and 6 months]

   Change from baseline (Day 0) in corrected distance visual acuity at Day 180. Corrected visual acuity was obtained using the subject's own glasses (for subjects that wear glasses) and measured in logMAR (log of the Minimum Angle of Resolution) units using an appropriate eye chart. A logMAR score of 0.0 is equivalent to a visual acuity of 20/20 and larger logMAR values indicate a poorer visual acuity (eg. A value of 0.3 corresponds to a visual acuity of 20/40).

2. Slit Lamp Biomicroscopy [6 months]

   Number of subjects with clinically significant (CS) findings noted from the slit lamp biomicroscopy examinations. A slit lamp biomicroscopy examination of the eyelids, cornea, conjunctiva, anterior chamber, and lens was performed at each visit for each eye. The results were graded as normal, abnormal not clinically significant (NCS), or abnormal CS. In addition, the cornea was scored specifically for corneal edema using a 4-point scale (0=None, +1=Mild, +2=Moderate and +3=Severe). An increase in corneal edema grade of two or more was considered clinically significant and evaluated as a potential AE by the investigator.

Other Outcome Measures

1. Device-related Adverse Events [6 months]

   Number of subjects who experienced any device-related adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with moderate to severe dry eye disease

• Literate, able to speak English or Spanish, and able to complete questionnaires independently

• Willing to sign the informed consent and deemed capable of complying with the requirements of the study protocol

Exclusion Criteria:

• Chronic or recurrent epistaxis, coagulation disorders or other conditions that, in the opinion of the investigator, may lead to clinically significant increased bleeding

• Nasal or sinus surgery (including history of application of nasal cautery) or significant trauma

• Cardiac demand pacemaker, implanted defibrillator or other implanted electronic device

• Diagnosis of epilepsy

• Corneal transplant in either or both eyes

• Participation in any clinical trial with a new active substance or a new device within 30 days of the Screening Visit

• Women who are pregnant, planning a pregnancy, or nursing at the Screening Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cornea & Cataract Consultants of Arizona	Phoenix	Arizona	United States	85032
2	Andover Eye Associates	Andover	Massachusetts	United States	01810
3	Total Eye Care	Memphis	Tennessee	United States	38119

Sponsors and Collaborators

• Oculeve, Inc.

Investigators

• Study Director: Edward Holland, MD, Cincinnati Eye Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oculeve, Inc.
• ClinicalTrials.gov Identifier: NCT02526290
• Other Study ID Numbers: OCUN-010
• First Posted: Aug 18, 2015
• Last Update Posted: Oct 31, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis

Study Results

Participant Flow

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Period Title: Overall Study
STARTED	97
COMPLETED	89
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Overall Participants	97
Age, Customized (participants) [Number]
< 50 years	15 15.5%
50 to <60 years	25 25.8%
60 to <70 years	40 41.2%
≥70 years	17 17.5%
Sex: Female, Male (Count of Participants)
Female	77 79.4%
Male	20 20.6%

Outcome Measures

1. Primary Outcome

Title	Stimulated Acute Tear Production
Description	Stimulated acute tear production in the study eye at Day 180 as measured by the difference between the Schirmer test score during stimulation and the test score before stimulation (basal). The Schirmer strip is placed just under the eyelid and wicks up the tears. It measures tear production on a linear scale of 0-35 mm.
Time Frame	The stimulated and prestimulation (basal) measures were both performed at Day 180.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) population included all subjects who received an investigational device and initiated neurostimulation.

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Measure Participants	89
Stimulated Schirmer Test	17.28 (11.948)
Unstimulated Schirmer Test	7.92 (6.386)

2. Secondary Outcome

Title	Corrected Distance Visual Acuity
Description	Change from baseline (Day 0) in corrected distance visual acuity at Day 180. Corrected visual acuity was obtained using the subject's own glasses (for subjects that wear glasses) and measured in logMAR (log of the Minimum Angle of Resolution) units using an appropriate eye chart. A logMAR score of 0.0 is equivalent to a visual acuity of 20/20 and larger logMAR values indicate a poorer visual acuity (eg. A value of 0.3 corresponds to a visual acuity of 20/40).
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received an investigational device and initiated neurostimulation.

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Measure Participants	94
Right Eye	-0.028 (0.0905)
Left Eye	-0.033 (0.0809)

3. Secondary Outcome

Title	Slit Lamp Biomicroscopy
Description	Number of subjects with clinically significant (CS) findings noted from the slit lamp biomicroscopy examinations. A slit lamp biomicroscopy examination of the eyelids, cornea, conjunctiva, anterior chamber, and lens was performed at each visit for each eye. The results were graded as normal, abnormal not clinically significant (NCS), or abnormal CS. In addition, the cornea was scored specifically for corneal edema using a 4-point scale (0=None, +1=Mild, +2=Moderate and +3=Severe). An increase in corneal edema grade of two or more was considered clinically significant and evaluated as a potential AE by the investigator.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received an investigational device and initiated neurostimulation.

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Measure Participants	97
Number [participants]	0 0%

4. Other Pre-specified Outcome

Title	Device-related Adverse Events
Description	Number of subjects who experienced any device-related adverse events.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received an investigational device and initiated neurostimulation.

Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
Measure Participants	97
Serious device-related AEs	0 0%
Non-serious device-related AEs	36 37.1%

Adverse Events

Time Frame	6 months
Arm/Group Title	Active - Device
Arm/Group Description	The Oculeve Intranasal Lacrimal Neurostimulator will be administered two to ten times per day for up to three minutes per administration. Intranasal Lacrimal Neurostimulator (Oculeve): Neurostimulation device
All Cause Mortality
	Active - Device
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Active - Device
	Affected / at Risk (%)	# Events
Total	8/97 (8.2%)
Infections and infestations
Pneumonia	1/97 (1%)
Musculoskeletal and connective tissue disorders
Left-sided lower back pain with left-sided sciatica	1/97 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/97 (1%)
Chronic lymphocytic leukemia	1/97 (1%)
Lung adenocarcinoma	1/97 (1%)
Psychiatric disorders
Manic episode secondary to medication non-compliance for bipolar disorder	1/97 (1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/97 (1%)
Shortness of breath (asthma)	1/97 (1%)
Other (Not Including Serious) Adverse Events
	Active - Device
	Affected / at Risk (%)	# Events
Total	40/97 (41.2%)
Infections and infestations
Cold/flu symptoms	18/97 (18.6%)
Product Issues
Transient electrical discomfort	5/97 (5.2%)
Respiratory, thoracic and mediastinal disorders
Nasal pain or discomfort	11/97 (11.3%)
Nosebleed	6/97 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.