Diabetic RetinopathyRIC-NPDRNCT06713720
Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy
A study testing Remote Ischemic Conditioning Device in people with Diabetic Retinopathy and Non-Proliferative Diabetic Retinopathy, run by Xuxiang Zhang, MD at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Diabetic Retinopathy, Non-Proliferative Diabetic Retinopathy, Remote Ischemic Conditioning
- What is being tested?
- Remote Ischemic Conditioning Device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 2 sitesChina
- Study dates
- 20 Apr 2025to 31 May 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100730
Shan He, 008619800328290, shanhe829@163.com
- Not yet recruiting
Xuanwu Hospital
Beijing, Beijing Municipality, 100730
珊 He, 86+19800328290, shanhe829@163.com
About this study
Official title: 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:
Read more
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.
Read the 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
- Being tested
- Remote Ischemic Conditioning Device, Sham Remote Ischemic Conditioning Device
- Keywords
- Non-Proliferative Diabetic Retinopathy, Diabetic Retinopathy, Retinal Neurovascular Unit, Remote Ischemic Conditioning, Randomized Controlled Trial
- Medical subject headings
- Diabetic Retinopathy, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote Ischemic Conditioning DeviceDevice
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 DeviceDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Remote Ischemic Conditioning Group | Experimental | 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. Receives: Device: Remote Ischemic Conditioning Device |
| Sham Remote Ischemic Conditioning Group | Sham comparator | 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. Receives: Device: Sham Remote Ischemic Conditioning Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 1 year after intervention
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 1 year after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2024
- Study start20 Apr 2025
- Primary completion30 Apr 2026 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuxiang Zhang, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Xuanwu Hospital, Beijing
- Responsible party
- Sponsor-investigator, Xuxiang Zhang, MD, Xuanwu Hospital, Beijing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06713720
- Sponsor's protocol ID
- CFH2024-2-20113
- Other IDs
- CFH2024-2-20113
- Acronym
- RIC-NPDR
- Status last verified
- Jun 2025
- First submitted
- 21 Nov 2024
- Last updated
- 26 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang XZ, He S, Li Z, Ren CH, Zhang XX. Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy (RIC-NPDR): study protocol for a randomized controlled trial. BMC Complement Med Ther. 2026 Mar 10;26(1):144. doi: 10.1186/s12906-026-05340-3.
PubMed 41803826
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy (RIC-NPDR)
- ClinicalTrials.gov ID
- NCT06713720
- Acronym / sponsor ID
- RIC-NPDR / CFH2024-2-20113
- Conditions
- Diabetic Retinopathy, Non-Proliferative Diabetic Retinopathy, Remote Ischemic Conditioning, Diabetes Mellitus, Type 2, Randomized Controlled Trial
- Keywords
- Non-Proliferative Diabetic Retinopathy, Diabetic Retinopathy, Retinal Neurovascular Unit, Remote Ischemic Conditioning, Randomized Controlled Trial
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Xuxiang Zhang, MDUniversity, hospital or other
- Collaborators
- Xuanwu Hospital, Beijing
- Study start
- 20 Apr 2025 (actual)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 3 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remote Ischemic Conditioning Group | Experimental | Device: Remote Ischemic Conditioning DeviceParticipants 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. |
| Sham Remote Ischemic Conditioning Group | Sham comparator | Device: Sham Remote Ischemic Conditioning DeviceParticipants 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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote Ischemic Conditioning DeviceParticipants 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. | Device | Remote Ischemic Conditioning Group |
| Sham Remote Ischemic Conditioning DeviceParticipants 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. | Device | Sham Remote Ischemic Conditioning Group |
Primary outcome
Change in Diabetic Retinopathy Severity Score (DRSS)
Time frame: 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.
5 secondary outcomes
Incidence of Proliferative Diabetic Retinopathy (PDR)
Time frame: 1 year after intervention
Change in Retinal Neurovascular Unit Parameters
Time frame: Baseline and 1 year after intervention
Change in Retinal Oxygen Saturation
Time frame: Baseline and 1 year after intervention
Change in Visual Acuity
Time frame: Baseline and 1 year after intervention
Change in Serum Biomarker Levels
Time frame: Baseline and 1 year after intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Derived from this study: PubMed 41803826Wang XZ, He S, Li Z, Ren CH, Zhang XX. Remote Ischemic Conditioning for Non-Proliferative Diabetic Retinopathy (RIC-NPDR): study protocol for a randomized controlled trial. BMC Complement Med Ther. 2026 Mar 10;26(1):144. doi: 10.1186/s12906-026-05340-3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote Ischemic Conditioning Device in people with Diabetic Retinopathy and Non-Proliferative Diabetic Retinopathy, run by Xuxiang Zhang, MD at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shan He (86+19800328290, shanhe829@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Diabetic Retinopathy Severity Score (DRSS) (time frame: Baseline and 1 year after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06713720, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.