Exosomes Proteomic for Sjogren's Syndrome and Dry Eye Syndrome

Recruiting

• Conditions: Dry Eye Syndrome (DES); Sjogren's Syndrome; Xerophthalmia
• Interventions: Other: acupuncture GB20 or GB20 plus BL2; Drug: Chinese herbal tea TBDESJS

• Registration Number: NCT06771427
• Lead Sponsor: Taipei Veterans General Hospital, Taiwan

Brief Summary

By analyzing the differential proteins in exosomes, this study aims to understand the pathological mechanisms of SJS and DES, identify potential diagnostic and therapeutic methods, and advance the diagnosis and treatment of these diseases.

Detailed Description

Background: A 2015 survey in Taiwan revealed that the prevalence of Dry Eye Syndrome (DES) is 4.87%, with 4.8% of these cases likely to develop into Sjögren's Syndrome (SJS). An American study indicated that 11.6% of DES cases could be diagnosed as SJS, and SJS patients showed significantly more severe conjunctival and corneal staining, Schirmer's test results, clinical symptoms, anti-nuclear antibody, and rheumatoid factor compared to non-SJS patients. Various autoimmune diseases (such as SJS, SLE, RA, SSc, AS, etc.) also affect the severity of dry eye symptoms. Recent studies have employed exosome proteomics to investigate cell-to-cell communication, molecular mechanisms of diseases, and the development of new diagnostic markers and therapeutic targets. While these studies have significant research value for understanding disease mechanisms, diagnosis, and treatment, few have specifically focused on the impact of exosome proteomics in SJS and DES.

Objective: By analyzing the differential proteins in exosomes, this study aims to understand the pathological mechanisms of SJS and DES, identify potential diagnostic and therapeutic methods, and advance the diagnosis and treatment of these diseases.

Methods: This study will develope on previous research projects conducted at Taipei Veterans General Hospital (TBDESJS，V112C-190) and the National Science and Technology Council (ACUDES). TBDESJS focused on evaluating the use of a herbal tea TBDESJS for relieving dry eye and mouth symptoms in DES and SJS patients, and ACUDES explored the immediate and long-term effects of acupuncture on treating dry eye and mouth symptoms in DES and SJS patients by using the GB20 (Fengchi) and BL2 (Zanzhu) acupuncture points.

1. TBDESJS Study: Included 30 DES patients, 60 SJS patients, and 10 healthy controls (NHC) to evaluate the efficacy of the Traditional Chinese Medicine (TCM) herbal tea in improving dry eye and mouth symptoms.

2. ACUDES Study: Included 50 DES patients, 50 SJS patients, and 20 NHC to evaluate the efficacy of acupuncture GB20 and BL2 in improving dry eye and mouth symptoms.

The study will further analyze the remaining samples from these two projects with consent from the participants (45 SJS, 28 DES, and 10 NHC from TBDESJS; 47 SJS, 40 DES, and 20 NHC from ACUDES). In total, 92 SJS, 68 DES, and 30 NHC participants will be included. We will select 40 participants with significant therapeutic improvement from the ACUDES study and 40 from the TBDESJS study for pre- and post-treatment comparison, along with 20 NHC participants, total 100 subjects and 180 person-times.

Additionally, we will perform comprehensive cross-analyses incorporating whole-genome genotyping, cytokines, Schirmer's test, tear breakup time, TCM constitution scale, OSDI, ESSPRI, PSQI, FIRST, TCM pulse diagnosis, TCM tongue diagnosis, and TCM heart rate variability measurements. This will help us understand the potential pathways by which the TBDESJS and ACUDESJS regulate immunity, aiming for future clinical applications in SJS and DES patients, ultimately achieving the goal of Holistic Health Care.

Expected Outcomes:

1. Purify exosomes from the plasma of SJS and DES patients, identify differential proteins between healthy individuals and patients, and investigate the roles of these proteins in immune cell regulation and their potential as diagnostic tools.

2. Analyze the differential proteins in plasma exosomes of SJS and DES patients before and after treatment with the TBDESJS and ACUDES to explore their therapeutic mechanisms.

3. Explore the possible pharmacological mechanisms of the TBDESJS and ACUDES.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-13
• Last Update Submitted: 2025-01-15
• Study Start: 2025-01-16
• Last Update Posted: 2025-01-17
• Primary Completion: 2025-04-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

aged between 20 and 75 years Schirmer's test less than 10 mm/5 min

Exclusion Criteria

Pregnancy With eye inflammation or infectious eye disease Accepted operation of eye Sjögren's syndrome

Inclusion Criteria: primary or secondary SS aged between 20 and 75 years fulfilled the 2002 American-European Consensus Criteria for SS (AECG) had no abnormal findings of immune, liver, kidney, or blood function evaluations.

Exclusion Criteria: a history of alcohol abuse, diabetes mellitus, or major life-threatening condition pregnancy or breastfeeding steroid pulse therapy within three months prior to the commencement of our study.

non AIDDES Healthy Controls

Inclusion Criteria: aged between 20 and 75 years without any Chronic disease Exclusion Criteria: any Sjögren's syndrome or Dry eye syndrome.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group GB20	acupuncture GB20 or GB20 plus BL2	Group GB20 will received acupuncture at acupoint GB20 twice a week 8 weeks for efficacy evaluation. And we could use the proteomic, exosome-proteomic, , exosome-miRNA, transcriptome, oral microbiota, Schirmer's test, Tear breakup time, 6-GSI, OSDI, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
Group GB20 plus BL2	acupuncture GB20 or GB20 plus BL2	Group GB20 plus BL2 will received acupuncture at acupoint GB20 plus BL2 twice a week 8 weeks for efficacy evaluation. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, oral microbiota, Schirmer's test, Tear breakup time, 6-GSI, OSDI, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
non AIDDES Healthy Controls (NHC)	acupuncture GB20 or GB20 plus BL2	ACUDES: Healthy control group will not received any treatment. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, oral microbiota, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability to find the difference with the comparison between the dry eye syndrome and healthy control. TBDESJS: Non DES SJS Healthy Controls (NHC) will received Chinese herbal tea TBDESJS 8 weeks on Nourishing Yin and Moistening Dryness the ocular dryness evaluation. And we could use the Schirmer's test, Tear breakup time, Ocular Surface Disease Index (OSDI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), cytokine markers, Whole-genome genotyping, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
non AIDDES Healthy Controls (NHC)	Chinese herbal tea TBDESJS	ACUDES: Healthy control group will not received any treatment. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, oral microbiota, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability to find the difference with the comparison between the dry eye syndrome and healthy control. TBDESJS: Non DES SJS Healthy Controls (NHC) will received Chinese herbal tea TBDESJS 8 weeks on Nourishing Yin and Moistening Dryness the ocular dryness evaluation. And we could use the Schirmer's test, Tear breakup time, Ocular Surface Disease Index (OSDI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), cytokine markers, Whole-genome genotyping, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
Dry eye syndrome (DES)	Chinese herbal tea TBDESJS	Dry eye syndrome (DES) will received Chinese herbal tea TBDESJS 8 weeks on Nourishing Yin and Moistening Dryness the ocular dryness evaluation. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, Schirmer's test, Tear breakup time, Ocular Surface Disease Index (OSDI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), cytokine markers, Whole-genome genotyping, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
Waiting list	Chinese herbal tea TBDESJS	Group Waiting list will not received any treatment. at acupoint GB20 plus BL2 twice a week 8 weeks for efficacy evaluation. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, oral microbiota, Schirmer's test, Tear breakup time, 6-GSI, OSDI, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.
Sjögren's syndrome (SJS)	Chinese herbal tea TBDESJS	Sjögren's syndrome (SJS) will received Chinese herbal tea TBDESJS 8 weeks on Nourishing Yin and Moistening Dryness the ocular dryness evaluation. And we could use the proteomic, exosome-proteomic, exosome-miRNA, transcriptome, Schirmer's test, Tear breakup time, Ocular Surface Disease Index (OSDI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), cytokine markers, Whole-genome genotyping, TCM pattern, Traditional Chinese Medicine (TCM) tongue diagnosis, TCM pulse diagnosis, and TCM heart rate variability for this purpose.

Primary Outcome Measures

Name	Time	Method
Schirmer's test	8 weeks	Dry eye syndrome (DES) and Sjögren's syndrome (SJS) take the Schirmer's test.
Ocular Surface Disease Index (OSDI)	8 weeks	Dry eye syndrome (DES) and Sjögren's syndrome (SJS) take the OSDI(Ocular Surface Disease Index).

Secondary Outcome Measures

Name	Time	Method
TCM tongue diagnosis	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the TCM tongue diagnosis with camera photo to differentiate the TCM tongue feature factors about Tongue body, Tongue Coating, Red spot, Tooth marks, and Ecchymosis. TCM tongue feature factors would present the status of inflammation, blood stasis, heat, dampness with TCM theory.
TCM heart rate variability	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the TCM heart rate variability.
Whole-genome genotyping(TWBv2.0)	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the Whole-genome genotyping (TWBv2.0).
Cytokine markers	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC) take the cytokine markers (IL-17, MMP-9, BAFF, BCMA) analysis.
Pittsburgh Sleep Quality Index	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC) take the Pittsburgh Sleep Quality Index
Tear breakup time (TBUT)	8 weeks	Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease.
Exosome-miRNA, transcriptome	8 weeks	exosome-miRNA, transcriptome can be used to assess for Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC)
TCM pattern	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the TCM pattern to differentiate the 9 types of TCM constitutions.
TCM pulse diagnosis	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the TCM pulse diagnosis with blood pressure monitors to differentiate the TCM pulse feature factors about Floating, Deep, Slow, Rapid, Deficient, Excessive, Slippery, Rough, String-like, Soggy, Fine, Weak. TCM tongue feature factors would present the status of inflammation, blood stasis, heat, dampness with TCM theory.
Ford Insomnia Response to Stress Test	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC) take the Ford Insomnia Response to Stress Test.
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)	8 weeks	Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC) take the EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
Proteomic, Exosome-proteomic	8 weeks	Proteomic, Exosome-proteomiccan be used to assess for Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC)

Trial Locations

Locations (1)

Ching-Mao; 🇨🇳 Taipei, Taiwan