Clinical trial NCT06475027: Exosome-miRNA and Transcriptome Profiling of Dry Eye Syndrome and Sjogren's Syndrome
Official title: Systematic Dissection of Exosome-miRNA and Transcriptome Profiling of Dry Eye Syndrome and Sjogren's Syndrome for Alleviating the Sicca Symptoms
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Dry Eye Syndrome
Sjogren's Syndrome
Xerophthalmia
Keywords: Dry eye syndrome
Sjögren's syndrome
Xerophthalmia
Acupuncture
Exosome
transcriptome
GB20
BL2
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2024-06-26
Enrollment: 220
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Schirmer's test
timeFrame: 8 weeks
measure: Ocular Surface Disease Index (OSDI)
timeFrame: 8 weeks
Secondary outcomes:
measure: TCM pattern
timeFrame: 8 weeks
measure: TCM tongue diagnosis
timeFrame: 8 weeks
measure: TCM pulse diagnosis
timeFrame: 8 weeks
measure: TCM heart rate variability
timeFrame: 8 weeks
measure: Whole-genome genotyping(TWBv2.0)
timeFrame: 8 weeks
measure: Cytokine markers
timeFrame: 8 weeks
measure: Pittsburgh Sleep Quality Index
timeFrame: 8 weeks
measure: Ford Insomnia Response to Stress Test
timeFrame: 8 weeks
measure: EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
timeFrame: 8 weeks
measure: Tear breakup time (TBUT)
timeFrame: 8 weeks
measure: Exosome-miRNA, transcriptome
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Ching-Mao Chang
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Ching-Mao Chang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: