Clinical trial NCT06089317: Traditional Chinese Medicine Ultrasonic Atomization Treatment for Dry Eye Disease
Official title: Traditional Chinese Medicine Ultrasonic Atomization Treatment for Dry Eye Disease: A Randomized, Double-masked, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dry Eye Syndromes
Keywords: Dry Eye Syndromes
Traditional Chinese Medicine
Ultrasonic Atomization
Randomized Controlled Trial
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2023-10-18
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of 200 subjects with mild to moderate DED will be recruited. Only one eye of recruited subjects with the shorter NIBUT will be selected and analyzed as the study eye. The subjects will be randomly divided into TCM compound decoction (CD) group, dendrobium caulis (DC) group, houttuynia cordata (HC) group, placebo atomization (PA) group, and artificial tears (AT) group equally. An online-based clinical trial randomization tool with a permuted block and stratification randomization method is applied for the randomization, and block sizes are randomly chosen. Stratification variances is sex and age.
Primary purpose: TREATMENT

Brief summary: Dry eye disease (DED) is the most prevalent ocular surface disease worldwide. Standard treatments like artificial tears show limited effect. Regarding the ultrasonic atomization, the ultrasonic nebulizer produces consistent steam from the solution with a treatment effect delivered to the ocular surface. We aim to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) ultrasonic atomization as an adjuvant treatment for DED.

This is a randomized double-masked, active- and placebo-controlled trial. 200 subjects will be equally assigned to the herbal compound decoction(CD) group, dendrobium caulis (DC) group, houttuynia cordata (HC) group, placebo atomization(PA) group, and artificial tear (AT) group by stratified permuted block randomization.

Subjects of CD, DC, HC, and PA groups will receive TCM ultrasonic atomization treatment (6 times/week). All patients will receive hypromellose 0.3% w/v lubricant eye drops for a 1-week wash-out and a 4-month follow-up period. Outcomes included non-invasive tear break-up times, corneal and conjunctival fluorescein staining, and other dry eye-related parameter examined by LipiView II Ocular Surface Interferometer, OCULUS® Keratograph 5M, and slit lamp biomicroscope evaluated by masked clinical assessors at baseline, week 1, 2, 3, 4 and month 2, 3, 4. The other subjective questionnaires like the Ocular Surface Disease Index (OSDI) questionnaire are also selected.


Eligibility criteria: Inclusion criteria:

1. At least one eye of subjects meets DED diagnostic criteria as the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS II); and
2. Ocular Surface Disease Index (OSDI)≥13 and \<33; and
3. The age range between years 18-80, no sex limitation; and
4. Symptoms of dry eye for at least 6 months; and
5. Can complete the questionnaires independently and understand Chinese or English.

Exclusion criteria:

1. Had or currently suffering from other concomitant ocular surface diseases, including chronic conjunctivitis, ocular rosacea, cicatricial pemphigoid, graft-versus-host disease, limbal stem cell deficiency, and severe ocular allergy;
2. Received any refractive surgery and corneal surgery before, including corneal transplant; or any eye surgery in the past 6 months;
3. Receiving DED-related medications, including topical steroid eyedrops, topical antibiotics, topical cyclosporin A, and topical diquafosol;
4. Received intense pulsed laser (IPL) or vectored thermal pulsation (VTP) therapy in the past 12 months;
5. Received topical antiglaucomatous treatment in the past 12 months
6. Plans to use contact lenses during treatment and follow-up periods or used contact lenses 2 weeks before the baseline measurement and recruitment;
7. Had or currently suffering from severe cardiopulmonary disease, liver and kidney dysfunction, and severe blood system diseases;
8. Suffering from glucose-6-phosphate dehydrogenase deficiency (G6PD);
9. Had or currently suffering from specific respiratory diseases, e.g. emphysema, bronchitis, asthma, chronic obstructive pulmonary disease, bronchial dilatation;
10. Has adverse reaction history to herbs used in this study before;
11. Whose TCM constitution is manifested as "yang-deficiency" or diagnosed by TCM practitioners that their TCM syndrome is not suitable for the atomization treatment;
12. Pregnancy, preparation for pregnancy, or lactation;

Primary outcomes:
measure: Change in the Ocular Surface Disease Index (OSDI)
timeFrame: baseline to 4th week
measure: Change in Non-invasive Tear Break-up Times (NIBUT)
timeFrame: baseline to 4th week
Secondary outcomes:
measure: Change in Ocular Surface Disease Index (OSDI)
timeFrame: 4 months
measure: Change in symptom Assessment iN Dry Eye (SANDE, modified)
timeFrame: 4 months
measure: Change in 36-Item Short Form Health Survey (SF-36)
timeFrame: 4 months
measure: Change in the Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI:GH)
timeFrame: 4 months
measure: Change in Non-Invasive Tear Break Up Times (NIBUT)
timeFrame: 4 months
measure: Changes in Tear Meniscus Height (TMH)
timeFrame: 4 months
measure: Changes in Bulbar Redness
timeFrame: 4 months
measure: Changes in Lipid Layer Thickness
timeFrame: 4 months
measure: Changes in Partial Blinking Rate
timeFrame: 4 months
measure: Changes in Meiboscore
timeFrame: 4 months
measure: Change in Tear Film Breakup Time (TBUT)
timeFrame: 4 months
measure: Change in Corneal and Conjunctival Fluorescein Staining
timeFrame: 4 months
measure: Change in Expressibility of Meibomian Glands in the Meibomian Glands Yielding Liquid Secretion (MGYLS) (the inferior eyelid)
timeFrame: 4 months
measure: Change in Quality of Expressed Meibum
timeFrame: 4 months
measure: Change in Lid Margin and Eyelash Abnormalities
timeFrame: 4 months
measure: Change in Tear Film Osmolarity (TFO)
timeFrame: 4 months
measure: Changes in Schirmer I test
timeFrame: 4 months
measure: Changes in Matrix metallopeptidase 9 (MMP-9)
timeFrame: 4 months
measure: Adverse events (AEs)
timeFrame: 4 months
Other outcomes:
measure: Intraocular Pressure (IOP)
timeFrame: 4 months
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 4 months
measure: Change in Posterior Subcapsular of Lens
timeFrame: 4 months
measure: Change in Nuclear Color (NC) of Lens
timeFrame: 4 months
measure: Change in Cortical Cataract (C) of Lens
timeFrame: 4 months
measure: Change in Nuclear Opalescence (NO) of Lens
timeFrame: 4 months
measure: Change in Central Corneal Thickness (CCT) of Corneal Endothelium
timeFrame: 4 months
measure: Change in Corneal Endothelial Cell Density (CD) of Corneal Endothelium
timeFrame: 4 months
measure: Change in Number of Cells Counted (NUM) of Corneal Endothelium
timeFrame: 4 months
measure: Constitution in Chinese Medicine Questionnaire (CCMQ)
timeFrame: -1 week
measure: Change of α-diversity in Ocular Surface Microbiome
timeFrame: 4 months
measure: Change of β-diversity in Ocular Surface Microbiome
timeFrame: 4 months
measure: Relative Abundance in Ocular Surface Microbiome
timeFrame: 4 months
Locations:
city: Kowloon
country: Hong Kong
facility: The Chinese University of Hong Kong Eye Centre (CUHKEC)
city: Kowloon
country: Hong Kong
facility: Hong Kong Eye Hospital
city: Shatin
country: Hong Kong
facility: The CUHK Medical Centre (CUHKMC)
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Kelvin KL Chong, MBChB
role: PRINCIPAL_INVESTIGATOR
References: