Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy

NCT ID: NCT06713720

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-20
• Study Completion Date: 2026-05-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Remote Ischemic Conditioning Device

Intervention Type: 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 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.

Group Type: SHAM_COMPARATOR

Sham Remote Ischemic Conditioning Device

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: collaborator

Xuxiang Zhang, MD

OTHER

Sponsor Role: lead

Responsible Party

Xuxiang Zhang, MD

Director of Ophthalmology, Xuanwu Hospital

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Xuanwu Hospital

Beijing, Beijing Municipality, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Shan He

Role: CONTACT

shanhe829@163.com

86+19800328290

Facility Contacts

Shan He

Role: primary

shanhe829@163.com

008619800328290

珊 He

Role: primary

shanhe829@163.com

86+19800328290

Other Identifiers

CFH2024-2-20113

Identifier Type: -

Identifier Source: org_study_id

CFH2024-2-20113

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id