Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy

Not Applicable

Not yet recruiting

• Conditions: Diabetic Retinopathy; Non-Proliferative Diabetic Retinopathy; Remote Ischemic Conditioning; Randomized Controlled Trial; Diabetes Mellitus, Type 2

• Registration Number: NCT06713720
• Lead Sponsor: Xuxiang Zhang, MD

Brief Summary

The goal of this clinical trial is to evaluate whether remote ischemic conditioning (RIC) is a safe and effective treatment for non-proliferative diabetic retinopathy (NPDR) in adults aged 40-80 years with type 2 diabetes. The study aims to address the limitations of current treatments for NPDR by using RIC, a technique involving repeated cycles of ischemia and hypoxia stimulation to activate protective mechanisms against retinal damage.

The main questions it aims to answer are:

Does RIC improve the Diabetic Retinopathy Severity Score (DRSS) after one year of treatment? Does RIC reduce the incidence of vision-threatening proliferative diabetic retinopathy (PDR)? What are the changes in retinal neurovascular unit parameters, visual acuity, and retinal oxygen saturation after RIC treatment?

Participants will:

Undergo RIC therapy using a specialized device on both upper limbs (or a placebo intervention for the control group) for 1 year.

Complete 5 cycles of RIC or placebo treatment twice daily, 5 days per week. Receive routine care for diabetic retinopathy as per clinical guidelines.

Key outcome measures:

Primary outcome: Change in DRSS from baseline after one year. Secondary outcomes: Incidence of PDR, changes in visual acuity, retinal neurovascular unit measures, retinal oxygen saturation, and serum biomarkers (e.g., VEGF, CRP, IL-6).

This randomized, double-blind, placebo-controlled trial aims to recruit 68 participants to ensure 60 complete the study, accounting for a 13% dropout rate. The findings are expected to provide insights into RIC as a novel intervention for NPDR, reducing blindness risk and supporting future large-scale trials.

Detailed Description

Non-proliferative diabetic retinopathy (NPDR) represents an early yet critical stage of diabetic retinopathy, a leading cause of vision loss globally. Despite advancements in medical treatments such as anti-VEGF therapy and laser photocoagulation, there remains a significant gap in safe and effective interventions to halt or reverse NPDR progression. Current therapies often focus on advanced disease stages, leaving early-stage management a challenge.

Remote ischemic conditioning (RIC) introduces a novel, non-invasive approach to NPDR treatment. Based on the concept of "fighting hypoxia with hypoxia," RIC employs intermittent cycles of ischemia and reperfusion in the limbs to trigger endogenous protective mechanisms against hypoxic damage. Experimental studies have highlighted RIC's potential benefits, including enhanced retinal oxygenation, reduced pathological vascular proliferation, and preservation of retinal ganglion cells.

This study is designed as a randomized, double-blind, placebo-controlled clinical trial to evaluate RIC's safety and efficacy in adults aged 40-80 years with mild to moderate NPDR. The trial features meticulous inclusion and exclusion criteria to ensure the reliability of findings. Participants will undergo either RIC or placebo therapy using a specialized device. The RIC group will receive therapy at 200 mmHg inflation pressure, while the placebo group will undergo sham treatment at 60 mmHg. Both treatments will follow the same cycle and frequency, ensuring blinding is maintained.

The study's outcomes include comprehensive assessments of retinal structure and function, systemic biomarkers, and safety metrics. These encompass changes in Diabetic Retinopathy Severity Score (DRSS), retinal neurovascular parameters, visual acuity, and retinal oxygenation. Serum biomarkers such as VEGF, CRP, and IL-6 will provide insights into systemic inflammatory and vascular changes post-treatment.

The findings from this trial are expected to offer preliminary evidence on RIC as a safe and effective intervention for NPDR. This work aims to lay the groundwork for future large-scale studies and provide clinicians with a potential strategy to reduce the burden of diabetic retinopathy and its associated complications.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-03
• Study Start: 2025-04-20
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-04-30
• Primary Completion: 2026-04-30
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• Age between 40 and 80 years.
• Diagnosed with Type 2 diabetes mellitus.
• Diagnosed with mild to moderate non-proliferative diabetic retinopathy (NPDR) with a DR Severity Score (DRSS) grade of 20-47D.
• Capable of performing daily activities independently.
• Willing and able to provide informed consent.

Exclusion Criteria

• Presence of diabetic macular edema (macular thickness > 250 μm).
• Significant eye diseases affecting evaluation, such as high myopia, severe cataract, corneal leucoma, glaucoma, retinal detachment, retinal vein occlusion, congenital eye diseases, ocular tumors, or severe infection.
• History of ocular laser or intraocular surgery.
• Poor imaging quality due to refractive media opacity.
• Contraindication to fluorescein fundus angiography.
• Unstable blood glucose (HbA1c ≥ 8.0%) despite oral antidiabetic drugs.
• Severe diabetes complications within the past 6 months.
• Severe, sustained hypertension (systolic ≥ 180 mmHg or diastolic ≥ 110 mmHg).
• Body mass index (BMI) ≥ 28 kg/m².
• Hepatic or renal insufficiency: Alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of normal. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m². Urine albumin/creatinine ratio ≥ 30 mg/g.
• Myocardial infarction within the past 6 months.
• Neurological diseases such as Alzheimer's, Parkinson's, cerebrovascular disease, intracranial tumor, cerebrovascular malformation, or aneurysm.
• Contraindications to RIC, including one-sided subclavian artery stenosis, upper limb injuries or vascular diseases, or limb deformities.
• Severe systemic diseases, such as malignant tumors with a life expectancy of less than 24 months.
• Known pregnancy or breastfeeding.
• Participation in other experimental clinical studies.
• Any other conditions deemed unsuitable by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Diabetic Retinopathy Severity Score (DRSS)	Baseline and 1 year after intervention	The primary outcome measure is the change in the Diabetic Retinopathy Severity Score (DRSS) from baseline to 1 year after intervention. The DRSS is a standardized grading system used to assess the severity of diabetic retinopathy, with changes reflecting disease progression or improvement.

Secondary Outcome Measures

Name	Time	Method
Change in Visual Acuity	Baseline and 1 year after intervention	The change in best-corrected visual acuity (BCVA) measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart between baseline and 1 year after intervention.
Incidence of Proliferative Diabetic Retinopathy (PDR)	1 year after intervention	The incidence of participants who progress to proliferative diabetic retinopathy (PDR) within one year after the intervention. PDR progression is identified based on clinical examination and fundus photography.
Change in Serum Biomarker Levels	Baseline and 1 year after intervention	The change in serum levels of vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and occludin from baseline to 1 year. These biomarkers provide insights into systemic inflammation, vascular health, and blood-retinal barrier function.
Change in Retinal Neurovascular Unit Parameters	Baseline and 1 year after intervention	Changes in parameters of the retinal neurovascular unit, including macular capillary densities (superficial and deep), radial peripapillary capillary density, ganglion cell complex thickness, and retinal nerve fiber layer thickness, assessed through optical coherence tomography angiography (OCTA) from baseline to 1 year.
Change in Retinal Oxygen Saturation	Baseline and 1 year after intervention	The change in retinal oxygen saturation levels measured using retinal oximetry between baseline and 1 year after intervention. Improvements are expected to reflect reduced retinal hypoxia.

Trial Locations

Locations (1)

Xuanwu Hospital; 🇨🇳 Beijing, Beijing, China