Clinical trial NCT06771427: Exosomes Proteomic for Sjogren's Syndrome and Dry Eye Syndrome
Official title: Systemic Proteomic Analysis of Plasma Exosomes to Explore the Immunomodulation Reflected to Sjogren's Syndrome and Dry Eye Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dry Eye Syndrome (DES)
Sjogren's Syndrome
Xerophthalmia
Keywords: Dry eye syndrome
Sjögren's syndrome
Xerophthalmia
Chinese herbal tea
Nourishing Yin and Moistening Dryness
Exosome
GB20
BL2
proteomics
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2025-01-13
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: Dry Eye Syndrome (DES):

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

Sjögren's Syndrome (SS):Patients diagnosed with Sjögren's Syndrome, an autoimmune disorder marked by dry eyes and mouth, often accompanied by systemic manifestations.

non AIDDES Healthy Controls (NHC): Healthy individuals without any history of dry eye symptoms or autoimmune diseases, serving as a control group.

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.

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
measure: Proteomic, Exosome-proteomic
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Ching-Mao
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Ching-Mao Chang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin HC, Yen CM, Chen WS, Hsu CC, Kung YY, Wu JH, Su YT, Chen KF, Chen HY, Lien CM, Wang MJ, Chang CM. Unveiling the age-related dynamics in Sjogren's syndrome: Insights from heart rate variability and autonomic function. Int J Rheum Dis. 2024 Mar;27(3):e15088. doi: 10.1111/1756-185X.15088.
citation: Yen CM, Lin HC, Chen WS, Hsu CC, Liaw CC, Kung YY, Ma CP, Chen HY, Su YT, Chang CM. Evaluation of traditional Chinese medicine tea bag TBDESJS in patients with Sjogren's syndrome and dry eye syndrome: A phase II pilot study. Int J Rheum Dis. 2024 Nov;27(11):e15398. doi: 10.1111/1756-185X.15398.