Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy (RIC-NPDR)

Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy (RIC-NPDR)

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetic Retinopathy; Randomized Controlled Trial; Remote Ischemic Conditioning; Non-Proliferative Diabetic Retinopathy
• Intervention / Treatment: Device: Remote Ischemic Conditioning Device; Device: Sham Remote Ischemic Conditioning Device

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 Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shan He; Phone Number: 86+19800328290; Email: shanhe829@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Shan He; Phone Number: 008619800328290; Email: shanhe829@163.com
    • Beijing, Beijing, China, 100730
      • Not yet recruiting
      • Xuanwu Hospital
      • Contact: 珊 He; Phone Number: 86+19800328290; Email: shanhe829@163.com

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remote Ischemic Conditioning Group; Participants in this group will receive remote ischemic conditioning (RIC) therapy. This involves five cycles of 5-minute inflation at 200 mmHg followed by 5-minute deflation, twice daily, for at least five days per week over a one-year period.	Device: Remote Ischemic Conditioning Device; Participants in this group will use a remote ischemic conditioning device that applies five cycles of 5-minute inflation at 200 mmHg followed by 5-minute deflation on both arms, twice daily, for at least five days per week over one year. The device is designed to enhance retinal oxygenation and reduce hypoxia-related damage.
Sham Comparator: Sham Remote Ischemic Conditioning Group; Participants in this group will receive sham remote ischemic conditioning therapy. This involves the same device with inflation pressure set at 60 mmHg, following identical timing and frequency as the intervention group.	Device: Sham Remote Ischemic Conditioning Device; Participants in this group will use the same remote ischemic conditioning device set to an inflation pressure of 60 mmHg to simulate the treatment. This placebo intervention follows the same timing and cycle frequency as the active intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Diabetic Retinopathy Severity Score (DRSS)	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.	Baseline and 1 year after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Proliferative Diabetic Retinopathy (PDR)	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.	1 year after intervention
Change in Retinal Neurovascular Unit Parameters	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.	Baseline and 1 year after intervention
Change in Retinal Oxygen Saturation	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.	Baseline and 1 year after intervention
Change in Visual Acuity	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.	Baseline and 1 year after intervention
Change in Serum Biomarker Levels	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.	Baseline and 1 year after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Local Complications Related to Intervention	The incidence of experiencing local complications, including upper limb pain, erythema, edema, skin injury, and ischemia, related to the remote ischemic conditioning device during the one-year intervention period.	Up to 1 year during intervention
Retention Rate of Participants	The retention rate of participants who complete the one-year intervention without withdrawal. This measures feasibility and adherence to the intervention protocol.	1 year after intervention

Collaborators and Investigators

• Sponsor: Xuxiang Zhang, MD
• Collaborators: Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 22, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Remote Ischemic Conditioning; Diabetic Retinopathy; Non-Proliferative Diabetic Retinopathy; Retinal Neurovascular Unit
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Retinal Diseases; Diabetic Retinopathy; Ischemia; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CFH2024-2-20113 (Other Grant/Funding Number: Capital's Funds for Health Improvement and Research)

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
• product manufactured in and exported from the U.S.: No