Exosome-miRNA and Transcriptome Profiling of Dry Eye Syndrome and Sjogren's Syndrome

June 20, 2024 updated by: Taipei Veterans General Hospital, Taiwan

Systematic Dissection of Exosome-miRNA and Transcriptome Profiling of Dry Eye Syndrome and Sjogren's Syndrome for Alleviating the Sicca Symptoms

This study combines data from two trials testing acupuncture (ACUDES) and a Chinese herbal tea bag TBDESJS for Dry Eye Syndrome and Sjögren's syndrome. Both treatments improved tear production. Researchers will now analyze participants' blood remaining samples and other data to understand how these therapies work. They will use advanced methods to identify tiny RNA molecules and immune system activity. This integrated approach aims to explain how acupuncture and TBDESJS improve dryness and support their use in managing these conditions.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Objective: In this study, we aimed to evaluate the therapeutic efficacy and mechanism of acupuncture and Chinese herbal tea bag TBDESJS in patients with Dry Eye Syndrome (DES) and Sjögren's Syndrome (SJS).

Research Background: The ACUDES study, funded by the National Science Council, focuses on assessing the immediate and long-term therapeutic effects of acupuncture at the Fengchi GB20 and Zanzhu BL2 points, combined with a comprehensive analysis of oral microbiota. The TBDESJS study at Taipei Veterans General Hospital investigates the effectiveness of Chinese herbal tea bags TBDESJS in alleviating dryness symptoms in the mouth and eyes of patients with DES and SJS. Progress in the ACUDES and TBDESJS clinical trials indicates significant improvement in clinical efficacy before and after treatment in SJS and DES participants. After 16 weeks of treatment in the TBDESJS study, Schirmer's test showed a significant increase in tear secretion: 7.51-7.63 mm in the left eye (P<0.001) and 7.85-8.66 mm in the right eye (P<0.001). In ACUDES, SJS and DES participants were divided into Fengchi (GB) and Fengchi plus Zanzhu (GBL) groups, with Schirmer's test showing significant increases in tear secretion after 16 weeks of treatment: 6.44-7.51 mm in the left eye (P<0.001) and 6.44-7.51 mm in the right eye (P<0.001).

Methods: In the first year, this study will analyze remaining samples from TBDESJS and ACUDES participants, aiming to extend the analysis to 80 DES and 110 SJS participants, and 30 NHC, and then we identified the 40 DES participants and 60 SJS participants who exhibited the most significant therapeutic improvement pre- and post-treatment, alongside 30 healthy control subjects. The study will systematically analyze exosome-miRNA and transcriptome to investigate the possible mechanisms by which Chinese herbal tea bags and acupuncture alleviate dryness symptoms in the mouth and eyes. In the second year, the study will use machine learning (supervised learning with Random Forest, Support Vector Machine, Neural Networks, unsupervised learning with K-Means Clustering, Principal Component Analysis, Feature Engineering) and multidimensional statistical methods (descriptive statistics, principal component analysis, cluster analysis, multiple regression) to deeply analyze the comprehensive cross-analysis of Whole-genome genotyping, Cytokines, Schirmer's test, Tear breakup time, Traditional Chinese Medicine constitution, OSDI, ESSPRI, PSQI, FIRST, Traditional Chinese Medicine (TCM) pulse diagnosis, TCM tongue diagnosis, heart rate variability measurements, exosome-miRNA, and transcriptome from the earlier TBDESJS and ACUDES cases. This integrated, cross-disciplinary approach is expected to elucidate potential immunomodulatory pathways influenced by TBDESJS and acupuncture GB20 or BL2, thereby providing a foundational basis for their clinical application in managing DES and SJS, and advancing towards our ultimate goal of Holistic Health Care.

Expected Results:

  1. Analyze exosomes purified from plasma to identify differentially expressed small RNA molecules in SJS, DES, and NHC.
  2. Investigate the regulatory roles of small RNA molecules on immune cells.
  3. Explore the differential expression of small RNA molecules in exosomes before and after treatment with TBDESJS and acupuncture with GB20 or BL2 in SJS and DES participants.
  4. Investigate the potential pharmacological mechanisms of TBDESJS and acupuncture with GB20 or BL2.

Study Type

Observational

Enrollment (Estimated)

220

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ching-Mao Chang, M.D., Ph.D.
  • Phone Number: 333 88628757453
  • Email: magicbjp@gmail.com

Study Locations

  • Taiwan
      • Taipei, Taiwan, 112
        • Ching-Mao Chang

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

  1. Dry Eye Syndrome (DES):

    Participants diagnosed with Dry Eye Syndrome, characterized by symptoms such as ocular discomfort, dryness, and visual disturbances.

  2. Sjögren's Syndrome (SS):Patients diagnosed with Sjögren's Syndrome, an autoimmune disorder marked by dry eyes and mouth, often accompanied by systemic manifestations.
  3. non AIDDES Healthy Controls (NHC): Healthy individuals without any history of dry eye symptoms or autoimmune diseases, serving as a control group.

Description

Dry eye syndrome

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group GB20
Group GB20 will received acupuncture at acupoint GB20 twice a week 8 weeks for efficacy evaluation. And we could use the 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.
Other: Acupuncture
acupuncture GB20 or GB20 plus BL2
Group 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 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.
Other: Acupuncture
acupuncture GB20 or GB20 plus BL2
non AIDDES Healthy Controls (NHC)
  1. ACUDES: Healthy control group will not received any treatment. And we could use the 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.
  2. 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.
Other: Acupuncture
acupuncture GB20 or GB20 plus BL2
Waiting list
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 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.
Other: Acupuncture
acupuncture GB20 or GB20 plus BL2
Dry eye syndrome (DES)
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 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.
Other: TBDESJS
Chinese herbal tea TBDESJS
Sjögren's syndrome (SJS)
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 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.
Other: TBDESJS
Chinese herbal tea TBDESJS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Schirmer's test
Time Frame: 8 weeks
Dry eye syndrome (DES) and Sjögren's syndrome (SJS) take the Schirmer's test.
8 weeks
Ocular Surface Disease Index (OSDI)
Time Frame: 8 weeks
Dry eye syndrome (DES) and Sjögren's syndrome (SJS) take the OSDI(Ocular Surface Disease Index).
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TCM pattern
Time Frame: 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.
8 weeks
TCM tongue diagnosis
Time Frame: 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.
8 weeks
TCM pulse diagnosis
Time Frame: 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.
8 weeks
TCM heart rate variability
Time Frame: 8 weeks
Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the TCM heart rate variability.
8 weeks
Whole-genome genotyping(TWBv2.0)
Time Frame: 8 weeks
Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls (NHC) take the Whole-genome genotyping (TWBv2.0).
8 weeks
Cytokine markers
Time Frame: 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.
8 weeks
Pittsburgh Sleep Quality Index
Time Frame: 8 weeks
Dry eye syndrome (DES), Sjögren's syndrome (SJS), and on DES SJS Healthy Controls, NHC) take the Pittsburgh Sleep Quality Index
8 weeks
Ford Insomnia Response to Stress Test
Time Frame: 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.
8 weeks
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
Time Frame: 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)
8 weeks
Tear breakup time (TBUT)
Time Frame: 8 weeks
Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease.
8 weeks
Exosome-miRNA, transcriptome
Time Frame: 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)
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Investigators

  • Principal Investigator: Ching-Mao Chang, M.D., Ph.D., Taipei Veterans General Hospital, Taiwan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

June 11, 2024

First Submitted That Met QC Criteria

June 20, 2024

First Posted (Actual)

June 26, 2024

Study Record Updates

Last Update Posted (Actual)

June 26, 2024

Last Update Submitted That Met QC Criteria

June 20, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-11-004CC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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