Safety and Efficacy of Punctal Plug Insertion in Patients With Dry Eye

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01684436
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Actual Duration (Months): 10
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This study will access changes in tear protein levels and symptoms of dry eye following insertion of a punctal plug.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Device: Punctal Plug	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jul 31, 2013
• Actual Study Completion Date: Jul 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Punctal plug Punctal plugs inserted into the study eye on Day 1.	Device: Punctal Plug; Punctal plugs inserted into the study eye on Day 1.

Outcome Measures

Primary Outcome Measures

1. Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye [Week 0 (Baseline)]

   A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.

2. Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye [Week 3]

   A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.

Secondary Outcome Measures

1. Corneal Fluorescein Staining Score in the Study Eye [Week 0 (Baseline), Week 3]

   The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.

2. Tear Film Break-up Time (TBUT) [Week 0 (Baseline), Week 3]

   TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.

3. Schirmer's Test Score [Week 0 (Baseline), Week 3]

   The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.

4. Dry Eye Questionnaire Irritation Score [Week 0 (Baseline), Week 3]

   Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with moderate to severe dry eye

Exclusion Criteria:

• Previous punctal plug insertion in the last 3 months or presence of plugs at the time of study

• Contact lens wear in the 7 days prior to study start or during the study

• LASIK procedure in the last year

• Cataract or other eye surgery in the last 3 months

• Corneal grafts

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Singapore		Singapore

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Tong L, Beuerman R, Simonyi S, Hollander DA, Stern ME. Effects of Punctal Occlusion on Clinical Signs and Symptoms and on Tear Cytokine Levels in Patients with Dry Eye. Ocul Surf. 2016 Apr;14(2):233-41. doi: 10.1016/j.jtos.2015.12.004. Epub 2016 Jan 13.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01684436
• Other Study ID Numbers: APMA-DE-0812
• First Posted: Sep 13, 2012
• Last Update Posted: Apr 17, 2019
• Last Verified: Apr 1, 2019

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

Study Results

Participant Flow

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Overall Participants	29
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.8 (14.1)
Sex: Female, Male (Count of Participants)
Female	23 79.3%
Male	6 20.7%

Outcome Measures

1. Primary Outcome

Title	Concentration of Tear Cytokine Levels Before Punctal Plug Insertion in the Study Eye
Description	A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.
Time Frame	Week 0 (Baseline)

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
Interferon (IFN)	2.24 (2.02)
Interleukin-10 (IL10)	4.69 (3.54)
Interleukin-12 (IL12)	9.08 (9.98)
Interleukin-13 (IL13)	29.81 (26.53)
Interleukin-17A (IL17A)	0.57 (0.48)
Interleukin-1B (IL1B)	0.63 (0.37)
Matrix metallopeptidase 9 (MMP9)	1519.82 (1516.92)
Interleukin-2 (IL2)	0.88 (0.59)
Interleukin-4 (IL4)	17.66 (21.59)
Interleukin-6 (IL6)	6.11 (6.73)
Interleukin-8 (IL8)	74.00 (55.03)
Interferon γ-Induced Protein-10 (IP10)	2384.86 (1198.08)
Monocyte Chemotactic Protein 1 (MCP1)	49.08 (46.91)
Macrophage Inflammatory Protein 1 Alpha (MIP1A)	0.59 (0.56)
Regulate Activation Normal T-Cell Express (RANTE)	21.20 (15.57)
Tumor Necrosis Factor Alpha (TNFA)	1.54 (1.46)

2. Secondary Outcome

Title	Corneal Fluorescein Staining Score in the Study Eye
Description	The cornea is evaluated following ocular administration of fluorescein stain in the study eye. The cornea is the transparent front part of the eye which covers the iris and pupil. The cornea is divided into 5 regions. Each region is scored according to the extent of staining, with scores ranging from 0 to 4 points: 0=non-staining to 4=regional whole staining of the cornea with 0.5 unit intervals. The higher the staining score, the worse the dry eye condition.
Time Frame	Week 0 (Baseline), Week 3

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
Week 0 (Baseline): Superior	0.57 (0.85)
Week 0 (Baseline): Inferior	1.33 (0.93)
Week 0 (Baseline): Nasal	0.67 (0.89)
Week 0 (Baseline): Temporal	0.72 (0.96)
Week 0 (Baseline): Central	0.91 (0.95)
Week 3: Superior	0.48 (0.62)
Week 3: Inferior	1.22 (0.85)
Week 3: Nasal	0.41 (0.84)
Week 3: Temporal	0.36 (0.74)
Week 3: Central	0.57 (0.73)

3. Secondary Outcome

Title	Tear Film Break-up Time (TBUT)
Description	TBUT is defined as the time to initial breakup of the tear film following a blink. The longer it takes, the more stable the tear film.
Time Frame	Week 0 (Baseline), Week 3

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
Week 0 (Baseline)	2.21 (0.57)
Week 3	2.42 (0.76)

4. Secondary Outcome

Title	Schirmer's Test Score
Description	The Schirmer's Test measures the rate of tear secretion by the eye over 5 minutes (min). The results indicate the presence of dry eye (Normal = greater than or equal to 10 millimeters (mm) of tears, Dry Eye = less than 10 mm of tears). The smaller the number, the more severe the dry eye.
Time Frame	Week 0 (Baseline), Week 3

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
Week 0 (Baseline)	5.07 (2.76)
Week 3	6.28 (5.11)

5. Secondary Outcome

Title	Dry Eye Questionnaire Irritation Score
Description	Severity of dry eye irritation is rated by the patient using a visual analogue scale (VAS). Patients put a mark on a 100 millimeter line where 0 (far left on the line)=no symptoms to 100 (far right on the line)=most severe symptoms. The higher the score, the more severe the symptoms.
Time Frame	Week 0 (Baseline), Week 3

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
Week 0 (Baseline)	53.81 (26.5)
Week 3	36.22 (24.89)

6. Primary Outcome

Title	Concentration of Tear Cytokine Levels Following Punctal Plug Insertion in the Study Eye
Description	A punctal plug (tear duct plug) is a device inserted into the tear duct (puncta) of the eye to block the tear duct from draining liquid from the eye. Tears were collected using the Schirmer's test strip. Tears are measured in the study eye for tear cytokine levels before punctal plug insertion in picogram(pg)/milliliter (mL)/millimeter (mm) of Schirmer's test strip moistened. Cytokines help with the generation of an immune response. Increased cytokine levels are representative of inflammation in the eye.
Time Frame	Week 3

Outcome Measure Data

Analysis Population Description

All patients who completed the study

Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
Measure Participants	29
IFN	3.12 (2.69)
IL10	3.97 (3.35)
IL12	7.34 (6.05)
IL13	29.14 (23.35)
IL17A	0.55 (0.39)
IL1B	1.10 (1.03)
MMP9	1445.53 (1415.09)
IL2	1.05 (1.10)
IL4	9.75 (8.31)
IL6	4.31 (3.66)
IL8	61.07 (57.15)
IP10	2769.17 (1479.50)
MCP1	68.08 (62.10)
MIP1A	0.61 (0.73)
RANTE	29.55 (26.99)
TNFA	1.37 (1.21)

Adverse Events

Time Frame	Adverse events (AEs) and serious adverse events (SAEs) were collected over the 3 week study period.
Adverse Event Reporting Description	All patients enrolled in the study were used for the analysis of adverse events (AEs) and serious adverse events (SAEs).
Arm/Group Title	Punctal Plug
Arm/Group Description	Punctal plugs inserted into the study eye on Day 1.
All Cause Mortality
	Punctal Plug
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Punctal Plug
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	Punctal Plug
	Affected / at Risk (%)	# Events
Total	0/30 (0%)

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 at least 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.