to Evaluate the Effectiveness and Safety of the Tixel® , VS LipiFlow® in the Treatment of Meibomian Gland Dysfunction

Not Applicable

Completed

Conditions: Dry Eye
Meibomian Gland Dysfunction
Dry Eye Syndromes

Interventions: Device: LipiFlow
Device: Tixel C

Registration Number: NCT05162261

Lead Sponsor: Novoxel Ltd.

Brief Summary: A Randomized, Masked (Evaluator), Controlled, Prospective Study Evaluating the Effectiveness and Safety of the Tixel® Medical Device, Versus LipiFlow® in the Treatment of Meibomian Gland Dysfunction

Detailed Description: Randomized, open-label study comparing the Tixel device to LipiFlow System. Up to 110 patients (220 eyes) to be randomized in up to 5 clinical sites in the United States.

Evaluators will be masked as to the randomization assignments. Both eyes will receive the same randomized assignment and both eyes of each patient will be evaluated at all time points.

Data from both eyes will be using in the statistical analysis. The random-effects model adjusts the standard error (SE) and the confidence interval (CI) for within-person correlation between eyes.

Protocol Rev. 7.0 update: Addition of protocol extension to the current protocol: stage 1- main protocol for all patients and stage 2- extension protocol to a sub-group of patients only in the Tixel arm for additional follow-up visit 6 months post last treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 109

Inclusion Criteria

Age 22 years and older of any gender or race.
Provision of written informed consent prior to study participation.
Willingness and ability to return for all study visits.
Reports dry eye symptoms for three months prior to the study.
Ocular Surface Disease Index (OSDI) score between 23-79.
Tear break-up time (TBUT) <10 seconds in both eyes.
Agreement/ability to abstain from dry eye/MGD medications for the time between the treatment visit/s and the final study visit. Ocular lubricants are allowed if no changes are made during the study.
Reports having to use artificial tears or lubricants regulatory over the past month to relieve dry eye symptoms.
Meibomian gland obstruction in both eyes based on a total Meibomian Gland Secretion Score ≤12 in each eye.
At least 15 glands in each lower eyelid should be expressible, with a sterile cotton swab, at the slit lamp.

Main Study (Stage1)

Exclusion Criteria

History of ocular surgery including intraocular, oculo-plastic, corneal or refractive surgery within 6 months.
Patient with giant papillary conjunctivitis.
Patient with punctal plugs or who have had punctal cautery.
Ocular injury or trauma, chemical burns, or limbal stem cell deficiency within 3 months of the baseline examination.
Active ocular herpes zoster or simplex of eye or eyelid or a history of these any time.
Patient who are aphakic.
Cicatricial lid margin disease identified via slit lamp examination, including pemphigoid, symblepharon, etc.
Active ocular infection (e.g., viral, bacterial, mycobacterial, protozoan, or fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac, or eyelids including a hordeolum or stye).
Active ocular inflammation or history of chronic, recurrent ocular inflammation within prior 3 months (e.g., retinitis, macular inflammation, choroiditis, uveitis, iritis, scleritis, episcleritis, keratitis).
Ocular surface abnormality that may compromise corneal integrity (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy).
Lid surface abnormalities (e.g., entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, severe ptosis) that affect lid function in either eye.
Anterior blepharitis (staphylococcal, demodex or seborrheic grade 3 or 4).
Systemic disease conditions that cause dry eye (e.g., Stevens-Johnson syndrome, vitamin A deficiency, rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, leukemia, Riley-Day syndrome, systemic lupus erythematosus, Sjogren's syndrome).
Use of any of the following medications:
1. Systemic medication(s) that is known to cause ocular dryness (e.g. antihistamine, diuretics, anti-hypertensives, anti-depressants, hormone therapy) whose dose of this medication(s) has not been stable within 30 days prior to enrolment. There must be no anticipated adjustments to the dose of these medications for the duration of the trial;
2. Oral tetracyclines or azithromycin within 30 days prior to enrolment; or
3. Topical anti-glaucoma medications within 30 days prior to enrolment.
4. Any other systemic medication as per to the Investigator's discretion.
Women in childbearing age who are pregnant, nursing, or not utilizing adequate birth control measures.
Individuals using isotretinoin (Accutane) within 1 year, cyclosporine-A (Restasis) or lifitegrast ophthalmic solution (Xiidra) within 45 days prior to study treatment (day 0), or any other dry eye or MGD medications (antibiotics, non-steroidal anti-inflammatory drugs, corticosteroids) for at least 2 weeks and to maintain abstinence throughout the duration of the study (ocular lubricants are allowed if no changes are made during the study).
Individuals wearing contact lenses 1 month prior study treatment (day 0), and at any point during the study.
Current skin cancer, malignant sites and/or advanced premalignant lesions or moles in the treatment area.
An impaired immune system condition or use of immunosuppressive medication.
Collagen disorders, keloid formation and/or abnormal wound healing.
Previous invasive/ablative procedures in the areas to be treated within 3 months prior to initial treatment or plans for such treatment during the course treatment, or before complete healing of such treatments has occurred.
Any patient who takes or has taken any oral or topical medications, such as but not limited to topical retinoid (e.g., Retin-A), chemical peels, Latisse, Lash Boost which may cause fragile skin or impaired skin healing in the treatment area during the last 3 months and in the entire study period.
Any patient who has a history of bleeding coagulopathies.
Any patient who has tattoos or permanent makeup in the treated area.
Any patient who has burned, blistered, irritated, or sensitive skin in any of the areas to be treated.
Individuals using another ophthalmic investigational device or agent within 30 days of study participation.
Any of the following dry eye treatments:
1. Office-based dry eye treatment (e.g. IPL, LipiFlow, iLux, TearCare, Tixel, etc.) within 12 months prior to enrolment;
2. Meibomian gland expression within 6 months prior to enrolment;
3. Blephex or debridement within 3 months prior to enrollment is an exclusion;
4. Punctal occlusion or punctal plug placement within 30 days prior to enrolment;
5. Use of iTear or TrueTear device within the past 2 weeks. (Subjects must refrain from using these devices for the duration of the study.); or
6. Any history of meibomian gland probing
Use of at-home warm compresses or lid hygiene products while participating in study.
IOP higher than 19 mmHg.
Use of Botulinum-Toxin in the last 6 months prior to the treatment in the treatment area.
Any co-existing condition, either ocular or non-ocular that, in the judgement of the investigator, could affect the safety or effectiveness of treatment or the compliance of the subject to the protocol.

Study Extension (Stage 2)- Inclusion Criteria

Subjects who have completed the main study CLN 0858 (stage 1) in the Tixel arm.
TBUT -change from baseline in 1-month FU or 3-months FU was 2.5 seconds or above at least in one eye in the main study.
Provision of written informed consent for stage 2.
Agreement/ability to abstain from dry eye/MGD medications for the time in the extension study. Ocular lubricants are allowed if no changes are made during the study.

Study Extension (Stage 2)-Exclusion Criteria

* Same as in the main study (stage 1).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LipiFlow	LipiFlow	LipiFlow: Screening and baseline visits,Treatment session, followed by 2 Follow up sessions, 1and 3 months after the last treatment visit. Subject will be questioned about Discomfort and Pain Questionnaires (self-assessed) and OSDI questionnaire.
Tixel Group	Tixel C	Screening and baseline visits, Treatment- 3 treatment sessions, followed by 2 Follow up sessions, 1and 3 months after the last treatment visit. Subject will be questioned about Discomfort and Pain Questionnaires (self-assessed) and OSDI questionnaire.

Primary Outcome Measures

Name	Time	Method
Changes in Tear Break Up Times (TBUT) to the 4-weeks Follow-up Exam	Tixel arm: Baseline and 4 weeks after last treatment (8 weeks post baseline). LipiFlow arm: Baseline and 4 weeks after treatment (4 weeks post baseline).	Change from baseline to the 4-weeks follow-up exam in Tear Break Up Times (TBUT), as assessed by a masked rater. TBUT - Tear Break-Up Time, is a clinical test used to evaluate the stability of the tear film on the surface of the eye. It measures the time it takes for dry spots to appear on the cornea after a blink. A shorter TBUT indicates a more unstable tear film, which can be a sign of dry eye disease or other ocular surface disorders. Tear Break-Up Time (TBUT) is typically scored by the time (in seconds). The general interpretation of TBUT scores is as follows: Normal TBUT: More than 10 seconds Borderline TBUT: 5 to 10 seconds Abnormal/Low TBUT: Less than 5 seconds
Comparison of the Incidence of Device-related Ocular Adverse Events	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	Comparison of the incidence of device-related Ocular adverse events for the two treatment arms

Secondary Outcome Measures

Name	Time	Method
Changes in Patient OSDI	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	Change from baseline in patient symptoms using Ocular Surface Disease Index (OSDI) at 4-weeks and 12-weeks follow-up exam. The Ocular Surface Disease Index (OSDI) is a questionnaire designed to assess the severity of dry eye disease. OSDI Questionnaire The questionnaire consists of 12 questions divided into three subscales: Ocular Symptoms Visual Functioning Environmental Triggers Scoring System The scoring for the OSDI is based on a scale from 0 to 100, where higher scores indicate more severe symptoms. Each question is scored as follows: 0: None of the time 1. Some of the time 2. Half of the time 3. Most of the time 4. All of the time Interpretation of OSDI Scores The OSDI scores are generally interpreted as follows: 0-12: Normal or no dry eye 13-22: Mild dry eye 23-32: Moderate dry eye 33-100: Severe dry eye
Changes in Tear Break Up Times (TBUT) to the 12-weeks Follow-up Exam	Tixel arm: Baseline and 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline and 12 weeks after treatment (12 weeks post baseline).	Changes from baseline to the 12-weeks follow-up exam in Tear Break Up Times (TBUT), as assessed by a masked rater. BUT - Tear Break-Up Time, is a clinical test used to evaluate the stability of the tear film on the surface of the eye. It measures the time it takes for dry spots to appear on the cornea after a blink. A shorter TBUT indicates a more unstable tear film, which can be a sign of dry eye disease or other ocular surface disorders. Tear Break-Up Time (TBUT) is typically scored by the time (in seconds). The general interpretation of TBUT scores is as follows: Normal TBUT: More than 10 seconds Borderline TBUT: 5 to 10 seconds Abnormal/Low TBUT: Less than 5 seconds
Changes in MGS to 4-weeks and 12-weeks Follow-up Exam	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	score on a scale at baseline, 4-weeks and 12-weeks follow-up exam in Meibomian Gland (MGS), as assessed by a masked rater. The Meibomian Gland Score (MGS) is a clinical tool used to evaluate the function of the meibomian glands. Scoring Criteria Each gland is assessed and scored based on the quality of the expressed secretion: 0: No secretion 1. Inspissated 2. Cloudy 3. Clear liquid Interpretation of MGS Minimal MGS score = 0 in each eye (15 glands evaluated in each eye) Maximal MGS score = 45 in each eye (15 glands evaluated in each eye) Low MGS: (below 12) Indicates poor function or obstruction of the meibomian glands, suggesting MGD.
Score on a Scale During Treatment Discomfort and Pain Questionnaires (Each Self-assessed by VAS)	Tixel arm: 4 weeks (treatment 1- day 0, treatment 2- 2 weeks, treatment 3- 4 weeks). LipiFlow arm: On treatment day - day 0 (only one treatment for this arm)	Discomfort and Pain from the treatment (Tixel or LipiFlow) using the questionnaires assessed by the subject. These are visual analogue scale (VAS) questionnaires using a scale from 0-10 to assess eye discomfort and pain. Both questionnaires are to be self-assessed by the patient immediately following treatment. Interpetation for the assessment: score 0- no discomfort / pain score 5 - moderate discomfort / pain score 10 - worst possible discomfort / pain
Corneal Fluorescein Staining Slit Lamp Evaluation Scores and Change From Baseline	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	Changes from baseline following treatment for the test and control devices for the following assessments: Ocular Surface Staining (to evaluate the integrity of the corneal epithelium by identifying areas of damage or staining) Grading scale: 0 = Normal - No staining 1. = Mild - Superficial stippling micropunctate staining 2. = Moderate - Macropunctate staining with some coalescent areas 3. = Severe - Numerous coalescent macropunctate areas and/or patches 5 regions (superior, temporal, central, nasal, and inferior) are graded for each eye. total score range from 0 -15.
The Mean Changes From Baseline in IOP for All Eyes on the Tixel and Lipiflow Arms	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	Changes from baseline following treatment for the test and control devices for: Intraocular Pressure
Ocular Surface Conjunctival Lissamine Green Staining Changes From Baseline	Tixel arm: Baseline to 12 weeks after last treatment (16 weeks post baseline). LipiFlow arm: Baseline to 12 weeks after treatment (12 weeks post baseline).	Changes from baseline following treatment for the test and control devices for the following assessments: Lissamine staining scores (to assess the health of the conjunctival and corneal epithelium, particularly in dry eye disease, by identifying areas of damaged or dead cells). Grading scale: 0 = Normal - No staining 1. = Mild - Superficial stippling micropunctate staining 2. = Moderate - Macropunctate staining with some coalescent areas 3. = Severe - Numerous coalescent macropunctate areas and/or patches 6 regions (nasal, superior nasal, inferior nasal, temporal, superior temporal, inferior temporal) are graded for each eye. The total score range for each eye is 0-18.

Trial Locations

Locations (5): Moyes Eye Center
🇺🇸
Kansas City, Missouri, United States
Ophthalmology Associates
🇺🇸
Saint Louis, Missouri, United States
Visionary Research Institute
🇺🇸
Newport Beach, California, United States
PNV Clinical Research, LLC
🇺🇸
Texas City, Texas, United States
Gordon Schanzlin New Vision Institute
🇺🇸
La Jolla, California, United States