Electroacupuncture for Mild-to-moderate Dry Eye

Dry Eye Clinical Trial

Official title:

Multicenter, Randomized, Single-blinded, Sham-Controlled Trial of Electroacupuncture on Mild-to-moderate Dry Eye

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05552820
• Other study ID #: ShanghaiIAMM20220918
• Status: Recruiting
• Phase: N/A
• Start date: October 12, 2022
• Est. completion date: August 31, 2026

Study information

• Verified date: May 2024
• Source: Shanghai Institute of Acupuncture, Moxibustion and Meridian
• Contact: Guang Yang, MD
• Phone: +8618817818512
• Email: sunnyyang0415[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine if electroacupuncture acts as an dry eye treatment rather than a placebo, and identify if benefits are linked to corneal subbasal nerve changes and neuroimmunomodulatory indicators.

Description:

Acupuncture is an important method in the treatment of diseases in Chinese medicine and plays an important role in the treatment of many diseases. Electroacupuncture (EA), as a combination of acupuncture and electric stimulation, is now widely used in research and clinical treatment. Our preliminary study found that compared with 0.1% sodium hyaluronate eye drops, EA exerted more beneficial and durable effects after four weeks of treatment. However, the placebo effect of EA cannot be ruled out yet. The aim of this study is to determine if EA acts as an dry eye treatment rather than a placebo, and identify if benefits are linked to corneal subbasal nerve changes.

This is a multicenter, randomized, subject-blinded, sham-controlled trial. A total of 168 participants with mild-to-moderate dry eye will be randomly assigned (1:1) to verum EA or non-penetrating non-acupoint sham EA (3 times weekly for 4 weeks), followed by a 24-week follow-up. The primary efficacy outcome is the change from baseline to week 4 in the Noninvasive Tear Breakup Time (NIBUT). Secondary efficacy outcomes include tear meniscus height (TMH), Schirmer I test (SⅠT), corneal topography, corneal and conjunctival sensation, scores of Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS), Numerical rating scale (NRS), and Chinese Dry Eye Related Quality of Life Scale (CDERQOL) . Additionally, we will apply the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) to understand the mental health conditions of patients. IVCM will be performed to observe the morphological changes of the corneal basal nerve. The changes of NGF, CGRP, NPY, 8-OHDG, 4-HNE, MDA and other neuroimmunomodulatory indicators in tears and conjunctival cells will be detected by immunofluorescence, ELISA, or other techniques.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: August 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients meeting the diagnostic criteria for dry eye according to the TFOS DEWS ?

• Ages 18-65 years, no gender limit

Exclusion Criteria:

• Diagnosed with severe dry eye

• Combined with other eye diseases (e.g. severe blepharitis, blepharospasm, conjunctival laxity, strabismus, amblyopia, glaucoma, cataract, fundus disease, ocular trauma)

• With active eye diseases or a history of eye surgery within 3 months

• Received acupuncture treatment or other dry eye treatment measures within 1 month that may influence the assessment of efficacy

• Previously experienced electroacupuncture intervention

• Pregnant or breastfeeding females

• Serious systemic diseases such as cardiovascular, cerebrovascular, hepatic, renal, and hematopoietic system and psychiatric disorders

• With autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or ankylosing spondylitis

• With damaged, ulcerated, infected, or scarred skin at the selected acupoints

• Allergic to metal or tape

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Device:
• Verum Electroacupuncture
Acupoints: Cuanzhu (BL2), Taiyang (EX-HN5), Sibai (ST1), Sizhukong (TE23), Baihui (GV20), Fengchi (GB20), Hegu (LI4), Zusanli (ST36), Guangming (GB23), Sanyinjiao (SP6), and Taichong (LR3). All acupoints will be taken bilaterally, except Baihui (GV20). The subject is placed in the supine position with eyes close. After routine sterilization, the sterile polyethylene cylindrical needle pad will be adhered to the acupoints. Then, the sterile acupuncture needles (0.25 mm×0.40 mm, Hwato brand, China.) will be inserted into the skin through the needle pad. Twirling and lifting-thrusting manipulations will be performed on the acupoints until Deqi is reported by the subject. Two pairs of electrodes will be connected at the needle handles on BL2 and EX-HN5 with a 2 Hz, continuous-wave electro-stimulation provided by the electroacupuncture apparatus (SDZ-? type, Hwato brand, China). The pulse amplitude is about 1-2 mA.
• Sham Electroacupuncture
Sham acupoints: SA1(1 cm above BL2), SA2 (1 cm above SJ23),SA3 (1 cm above EX-HN5), SA4 (1 cm lateral to ST2), SA5 (the midpoint of the line between GV20 and right EX-HN1), SA6 (the midpoint of the line between GB20 and SJ16), SA7 (1 cm lateral to LI4), SA8 (the midpoint of the line between ST36 and GB34), SA9 (the midpoint of the line between GB37 and BL58), SA10 (1 cm backward to SP6), SA11 (the midpoint of the line between LR3 and SP4). After routine sterilization, placebo needles will be used (Streitberger, Asia-med GmbH). The tingling sensation produced when the Streitberger needle is fixed on the skin causes the subject to believe that the needle is piercing the skin, simulating a skin puncture. The electric stimulator is applied to bilateral SA1 and SA3 with no current output. The exterior appearance, indicator light, prompt tone of the sham device, and stimulation parameters are all indistinguishable from the normal one.

Locations

Country	Name	City	State
China	Guang Yang	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai Institute of Acupuncture, Moxibustion and Meridian	Eye & ENT Hospital of Fudan University, Shanghai Eye Disease Prevention and Treatment Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Generalized Anxiety Disorder (GAD-7)	The scale consists of 7 items with 4 frequency options for each question, ranging from "not at all (0)" to "almost every day (3)", with the following criteria: no anxiety (0-4); mild anxiety (5-9); moderate anxiety (10-14); and severe anxiety (15-21). 14 points); and severe anxiety (15-21 points).	Baseline, Week 4, Week 8, Week 16, Week 28
Other	Change From Baseline in Patient Health Questionnaire-9 (PHQ-9)	The scale consists of 9 items with 4 frequency options for each question, ranging from "not at all (0)" to "almost every day (3)", with the following criteria: no depression (0-4); mild depression (5-9); moderate depression (10-14); moderate to severe depression (15-19); and severe depression (20-27). 14 points); moderate to severe depression (15-19 points); and severe depression (20-27 points)	Baseline, Week 4, Week 8, Week 16, Week 28
Other	Change in morphological changes of the corneal basal nerve	In vivo confocal microscopy (IVCM) is performed to initially observe the morphological changes of the corneal basal nerve. IVCM images are taken with a Heidel-berg Retina Tomograph III (HRT III; Heidelberg Engi¬neering, Germany). The ACCMetrics analysis software (M.A. Dabbah, lmaging Science Biomedical Engineering, Manchester, UK) is used to calculate nerve morphological parameters for the selected images.	Baseline, Week 4
Other	Change in neuroimmunomodulatory indicators in tears and conjunctival cells	Schirmer test strip is s used to collect tears from patients before and after treatment. Conjunctival impression cytology is used to obtain conjunctival cells. Immunofluorescence, ELISA and other techniques are used to detect the changes in NGF, CGRP, NPY, 8-OHDG, 4-HNE, MDA and other neuroimmunomodulatory indicators in tears and conjunctival cells of subjects.	Baseline, Week 4
Primary	Change from Baseline in Noninvasive Tear Breakup Time (NIBUT)	The interval between a complete blink and the first breakup of tear film (indicated by a break or deformed Placido disc image on the screen) will be recorded. The measurements are carried out 3 times and the average value is considered as NIBUT.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Tear Meniscus Height (TMH)	The digital slit lamp (SL990N, CSO, Italy) is applied to take images of the tear meniscus at the lower lid margin in a dark room. The tear meniscus height directly below the central pupil is measured with the system's built-in caliper tool.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Ocular Surface Disease Index (OSDI)	The OSDI scale is used to assess subjective symptoms related to dry eye, including ocular symptoms, visual function and environmental triggers, with a total score ranging from 0 to 100. The higher the score, the more severe the subjective symptoms.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Corneal Fluorescein Staining (CFS)	Sodium fluorescein ophthalmic strips (Tianjin Jingming New Technology Development Co., Ltd., China) are used to evaluate corneal epithelial damage. According to the Oxford grading scheme, the CFS score ranges from 0 (no damage) to 5 (severe damage).	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Corneal Topography	The corneal topography system is used to take photographs. The subjects are asked to blink naturally 3 to 4 times, and after the last full blink, they look at the central light source of the Placido disk for 10 s. The researchers take photographs of the anterior corneal surface immediately after the blink and at 10 s of continuous gaze. The SRI and SAI are systematically analyzed and obtained at 10 s.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Corneal and Conjunctival sensation	The Cochet-Bonnet perception meter (Luneau Chartres, France) will be used to evaluate the corneal perception (including central, superior, inferior, nasal, and temporal corneas, all 2 mm from the corneal rim) and conjunctival perception (including temporal and nasal bulbar conjunctivae, both 3 mm from the corneal rim; superior and inferior conjunctiva, at the center of the eyelid). The measured fiber length will be converted to g/mm2 according to the criteria provided by the supplier, with a higher threshold indicating a more insensitive perception.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Schirmer I test (S?T)	S?T will be performed using a tear detection filter strip (Tianjin Jingming New Technology Development Co., Ltd., China). Patients are requested to avoid eye movement. The strips will be removed after 5 min, and recorded the wetting length.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Numerical Rating Scale (NRS)	Subjects are asked to rate their current Iocular pain intensity in the right and left eye (0-10 numerical rating scale, NRS) followed by placement of 0.4% hydroxybuprocaine hydrochloride (Santen Pharmaceutical Co., LTD., Japan), and rerating of pain 30 seconds later.	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Change From Baseline in Chinese Dry Eye Related Quality of Life Scale (CDERQOL)	CDERQOL includes 5 domians containing 45 items rated on a 5-point Likert scale ranging from 1 (completely disagree) to 5 (completely agree).	Baseline, Week 4, Week 8, Week 16, Week 28
Secondary	Adverse events	Any adverse events will be recorded. EA-related adverse events include local bleeding, subcutaneous hematoma, pain, itch, infection, and generalized symptoms such as dizziness and palpitation during treatment.	Week 4