Exploring the Interaction Between Metabolic Disorders and NLPR3 Inflammasome Activation in DR Inflammatory Damage (DR)

An Approach of Exploring the Mechanism of the Interaction Between Metabolic Disorders and NLPR3 Inflammasome Activation in DR Inflammatory Damage Based on Metabolomics Methods

Diabetic retinopathy (DR) is one of the most serious microvascular complications of diabetes. Early diagnosis and treatment of diabetes is the key to prevent visual impairment in DR patients. This study aims to use a non-targeted metabolomics detection technique combined with ultra-high performance liquid chromatography time-of-flight mass spectrometry to analyze the metabolomics profile in aqueous humor sample of DR patents, and further explore the mechanism of the relationship between differential metabolites and their metabolic pathways with NLRP3 activation in DR inflammatory damage. DR patients with macular edema will receive anti-vascular endothelial growth factor (anti-VEGF) treatment; these patients will be divided into two groups: responders group and non-responders group.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Retinopathy; Diabetic Macular Edema; Anti-vascular Endothelial Growth Factor

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Hui Chen, PHD; Phone Number: 0086-20-87330000; Email: chh5413@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510623
      • Zhongshan Ophthalmic Center of Sun Yat-Sen University
      • Contact: Zhongshan Ophthalmic Center of Sun Yat-sen University; Phone Number: 86+13560323773; Email: chh5413@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1. CON (non diabetes control group)：Non diabetes patients undergoing phacoemulsification surgery.
2. NDR (non diabetes retinopathy diabetes patients): Non DR diabetes patients undergoing phacoemulsification surgery.
3. NPDR (non proliferative diabetes retinopathy): DR patients with no sign of any neovascularization suggested by fluorescein sodium angiography and receiving intravitreal injection surgery.
4. PDR (proliferative diabetes retinopathy): DR patients with neovascularization suggested by fluorescein sodium angiography and receiving intravitreal injection surgery.

Description

Inclusion Criteria:

1. Patients > 40 years old.
2. CON (non diabetes control group)：patients undergoing phacoemulsification surgery.
3. NDR (non diabetes retinopathy diabetes patients): patients with diabetes history and undergoing phacoemulsification surgery.
4. NPDR (non proliferative diabetes retinopathy): patients with history of diabetes, fundus microangiopathy shown by fundus fluorescein angiography, including microangioma, hard exudation, wadding exudation and other non proliferative diabetes retinopathy signs, and did not receive invasive ophthalmic treatment within 3 months.
5. PDR (proliferative diabetes retinopathy): patients with a history of diabetes, fundus neovascular lesions shown by fundus fluorescein angiography, and did not receive invasive ophthalmic treatment within 3 months.
6. Patients voluntarily signed informed consent.

Exclusion Criteria:

1. CON (non diabetes control group)：patients with a history of other ophthalmic operations.
2. NDR (non diabetes retinopathy diabetes patients): patients with fundus changes of diabetes retinopathy or other ophthalmic surgery history.
3. NPDR (non proliferative diabetes retinopathy): patients with fundus neovascular lesions shown by fundus fluorescein angiography.
4. PDR (proliferative diabetes retinopathy):patients undergoing vitrectomy。
5. Patients with active ocular inflammation, high myopia, pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
CON(Non diabetes control group); Non diabetes patients undergoing phacoemulsification surgery
NDR(Non diabetes retinopathy diabetes patients); Non DR diabetes patients undergoing phacoemulsification surgery
NPDR (non proliferative diabetes retinopathy); DR patients with no sign of any neovascularization suggested by fluorescein sodium angiography and receiving intravitreal injection surgery
PDR (proliferative diabetes retinopathy); DR patients with neovascularization suggested by fluorescein sodium angiography and receiving intravitreal injection surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untargeted metabolomics for metabolic profile using UHPLC/MS	Aqueous humor samples in DR patients will be analysed to putatively identify metabolic profile by comparison with control samples using ultra-high performance liquid chromatography-high resolution mass spectrometer (UHPLC/MS). UHPLC/MS analysis allows the simultaneous high-resolution measurement of a broad range of metabolites, hence the untargeted nature of the analysis. For the UHPLC/MS results, perform normalization, standardization, and log transformation, then compare the metabolite differences between groups. Multivariate statistical analysis and Partial least squares discriminant analysis included in the mass spectrometry software will be used to analyse UHPLC/MS results to identify metabolites that best discriminate between DR and control conditions. The evaluation of significant metabolite results is based on: P-value and Fold change.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best-corrected visual acuity	Best-corrected visual acuity at baseline and 24 weeks follow-up	24 weeks
Central subfield thickness	Central subfield thickness at baseline and 24 weeks follow-up	24 weeks

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): July 3, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Diabetic retinopathy; metabolomics; Anti-vascular endothelial growth factor; NLPR3; Diabetic Macular edema
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Macular Edema; Metabolic Diseases
• Other Study ID Numbers: 2023KYPJ292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No