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Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis

Primary Purpose

Blepharoptosis, Synkinesis, Hyperkinesis

Status
Not yet recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Oxymetazoline 0.1% (Pf) Oph Soln Ud
Preservative free lubricating drops
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blepharoptosis focused on measuring acquired blepharoptosis, hyperkinesis, synkinesis, facial paralysis, aberrant regeneration syndrome, post-paralysis synkinesis, nonflaccid facial paralysis

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Over 18 years of age Primary diagnosis of nonflaccid facial paralysis (aberrant regeneration syndrome) and acquired blepharoptosis. Exclusion Criteria: Patients under the age of 18 Patients on cardiac glycosides Patients on MAO inhibitors Patients with angle closure glaucoma Patients who experience asymmetrical eye opening due to weakness (e.g. lagophthalmos).

Sites / Locations

  • M.S. Hershey Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Oxymetazoline 0.1% ophthalmic drops

Preservative free lubricating drops

Arm Description

Patients will use once daily in affected eye. Drops are provided in single use vials.

Patients will use once daily in affected eye. Drops are provided in single use vials.

Outcomes

Primary Outcome Measures

Difference from baseline to end of study in Sunnybrook Grading Score
Clinician-graded outcome measure
Difference from baseline to end of study Synkinesis Assessment Questionnaire
Patient reported outcome measure
Difference from baseline to end of study in Facial Disability Index
Disease-specific quality of life measure

Secondary Outcome Measures

Difference in MRD-1 from baseline to when medication is being used
Objective assessment of eyelid position relative to the pupillary light reflex as measured by clinician
Difference in palpebral height from baseline to when medication is being used
Width of ocular aperture from upper to lower eyelid

Full Information

First Posted
July 6, 2023
Last Updated
September 19, 2023
Sponsor
Milton S. Hershey Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05945615
Brief Title
Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis
Official Title
Evaluation of Ophthalmic Oxymetazoline as an Adjunct Treatment for Acquired Blepharoptosis Due to Periocular Synkinesis.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Milton S. Hershey Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
After an episode of facial paralysis, as nerves recover, they aberrantly regenerate and send additional branches to the incorrect muscles in addition to the intended muscle. This leads to what is known as Aberrant Regeneration Syndrome, Post-paralysis Synkinesis, or Nonflaccid Facial Paralysis. It is characterized by poor facial symmetry and function, hypertonic facial muscles at rest, and abnormal facial movements. One sequela is acquired blepharoptosis causing a smaller ocular aperture, visual field obstruction, cosmetic deformity, and abnormal periocular spasms. This study aims to evaluate an FDA approved medication for acquired blepharoptosis due to synkinesis/hyperkinesis as an adjunct to treatment.
Detailed Description
Broadly, synkinesis is a neuromuscular condition in which voluntary muscle contraction causes simultaneous involuntary contraction of other muscle groups e.g. pursing of the lips causes involuntary closure of the eye. It is a common sequelae of facial nerve paralysis with 55% or more of patients reporting synkinetic facial movement. 2 Additionally, patients may develop hyperkinesis due to continual firing of nerves that have aberrantly regenerated, thereby causing decreased movement due to antagonistic muscle hyperactivity, tightness, spasms, and pain. These together significant affect facial symmetry, aesthetics, and facial function. While the definitive pathophysiology of synkinesis is still unknown, the most supported theory describes neuronal miswiring (aberrant regeneration theory). It suggests that following injury to the facial nerve and Wallerian degeneration, axons from the facial nucleus in the brainstem regrow and form inappropriate connections to peripheral muscle groups (e.g. a nerve meant to control the orbicularis oris of the mouth connects to the orbicularis oculi of the eye as well). This results in involuntary facial movements during normal expression and can affect all muscles of facial expression. Furthermore, because of continual facial muscular tone or hypertonicity, this is not only a dynamic process, but a static one as well. Synkinesis and hypertonicity can cause facial asymmetry and a fixed immobile face ("frozen facies) due to opposing muscles constantly contracting and limiting movement. The result can be unaesthetic: the eyes may look smaller, the commissure (corner) of the mouth may look deviated up and out, the nasolabial fold may look deeper, the base of the nose may be deviated, the chin may be twisted or dimpled, and a band may be seen in the neck. This also presents functional limitations, such as difficulties in articulation, biting of the lip/cheek, nasal obstruction, incomplete oral competency with drooling, watering of the eye (epiphora) and in controlling facial expressions. Patients notice pain, tightness, poor facial movement, and difficulty expressing emotions, loss of their smile, and embarrassment. These limitations decrease confidence and ultimately the patient's quality of life. Our study intends to look specifically at periocular synkinesis with orbicularis oculi muscle hypertonicity resulting in acquired blepharoptosis over time (i.e. drooping of the eyelid). Periocular synkinesis is partial closure of the eye due to inappropriate contraction of the orbicularis oculi muscle during other facial movement. Hypertonicity of the orbicularis oculi muscle results in the static narrowing of the palpebral fissure (acquired blepharoptosis) and may cause visual obstruction, asymmetry, and an aged appearance in the affected eye and can occur with both dynamic movement and static tone (hyperkinesis). This facial movement disorder has no cure. Treatments are intended to improve facial symmetry, decreased tightness/pain, improve function and improve quality of life. These include facial therapy, chemodenervation injections with neurotoxins, and a variety of surgeries. Patients require multimodal therapy. None of these treatments adequately address the acquired blepharoptosis from chronic hyperkinesis and synkinesis. Oxymetazoline was initially developed in 1961. It is a direct sympathomimetic, binding directly to alpha-1 and alpha-2 receptors. Currently, it is used as a nasal decongestant, in the treatment of epistaxis, and as a topical treatment for rosacea. Previously, an ophthalmic formulation was used to treat eye redness and irritation as it is FDA approved for the treatment of acquired blepharoptosis. However, this product line was discontinued when in July of 2020, oxymetazoline received Food and Drug Administration approval for treatment of cosmetic blepharoptosis. In the treatment of blepharoptosis, oxymetazoline acts on the superior tarsal muscle, Müller's muscle, to elevate the eyelid. The superior tarsal muscle is a sympathetically innervated muscle that is partially responsible for elevating the eyelid. 5 Previous cosmetic studies have shown oxymetazoline can serve as an adjunct to botulinum toxin in patients with acquired blepharoptosis. However, no study has been performed evaluating oxymetazoline's efficacy as an adjunct to botulinum toxin in patients with acquired blepharoptosis secondary to hypertonicity and synkinesis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blepharoptosis, Synkinesis, Hyperkinesis, Facial Paralysis
Keywords
acquired blepharoptosis, hyperkinesis, synkinesis, facial paralysis, aberrant regeneration syndrome, post-paralysis synkinesis, nonflaccid facial paralysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Blinded, randomized, cross-over trial that will analyze and compare the efficacy of oxymetazoline drops alone, oxymetazoline drops adjunct with botulinum toxin, botulinum toxin alone, and no treatment.
Masking
Investigator
Masking Description
Participants in the study will be randomized 2:1 to treatment with oxymetazoline 0.1% or the vehicle solution. Randomization schemes were created by a biostatician. This will be stored in a secure database, only accessible to the investigators. Experimental drops and placebo drops will be removed from their labeled boxes and provided to patients with instructions on use.
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oxymetazoline 0.1% ophthalmic drops
Arm Type
Experimental
Arm Description
Patients will use once daily in affected eye. Drops are provided in single use vials.
Arm Title
Preservative free lubricating drops
Arm Type
Placebo Comparator
Arm Description
Patients will use once daily in affected eye. Drops are provided in single use vials.
Intervention Type
Drug
Intervention Name(s)
Oxymetazoline 0.1% (Pf) Oph Soln Ud
Other Intervention Name(s)
Upneeq
Intervention Description
Oxymetazoline was initially developed in 1961. It is a direct sympathomimetic, binding directly to alpha-1 and alpha-2 receptors. Currently, it is used as a nasal decongestant, in the treatment of epistaxis, and as a topical treatment for rosacea. Previously, an ophthalmic formulation was used to treat eye redness and irritation as it is FDA approved for the treatment of acquired blepharoptosis. However, this product line was discontinued when in July of 2020, oxymetazoline received Food and Drug Administration approval for treatment of cosmetic blepharoptosis. In the treatment of blepharoptosis, oxymetazoline acts on the superior tarsal muscle, Müller's muscle, to elevate the eyelid. The superior tarsal muscle is a sympathetically innervated muscle that is partially responsible for elevating the eyelid. Previous cosmetic studies have shown oxymetazoline can serve as an adjunct to botulinum toxin in patients with acquired blepharoptosis.
Intervention Type
Other
Intervention Name(s)
Preservative free lubricating drops
Other Intervention Name(s)
soothe
Intervention Description
Over the counter ophthalmic lubricating drop.
Primary Outcome Measure Information:
Title
Difference from baseline to end of study in Sunnybrook Grading Score
Description
Clinician-graded outcome measure
Time Frame
6 months
Title
Difference from baseline to end of study Synkinesis Assessment Questionnaire
Description
Patient reported outcome measure
Time Frame
6 months
Title
Difference from baseline to end of study in Facial Disability Index
Description
Disease-specific quality of life measure
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Difference in MRD-1 from baseline to when medication is being used
Description
Objective assessment of eyelid position relative to the pupillary light reflex as measured by clinician
Time Frame
6 months
Title
Difference in palpebral height from baseline to when medication is being used
Description
Width of ocular aperture from upper to lower eyelid
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Over 18 years of age Primary diagnosis of nonflaccid facial paralysis (aberrant regeneration syndrome) and acquired blepharoptosis. Exclusion Criteria: Patients under the age of 18 Patients on cardiac glycosides Patients on MAO inhibitors Patients with angle closure glaucoma Patients who experience asymmetrical eye opening due to weakness (e.g. lagophthalmos).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessyka Lighthall, MD
Phone
7175318945
Email
jlighthall@pennstatehealth.psu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessyka Lighthall, MD
Organizational Affiliation
Penn State Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
M.S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessyka Lighthall, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis

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