Tangningtongluo Tablet in the Treatment of Non-proliferative Diabetic Retinopathy

Study Overview
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Brief Summary
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This trial is planned to collect relevant clinical data to evaluate the prevention efficacy and safety of Tangningtongluo tablets on the non-proliferation period of diabetic retinopathy.

Detailed Description
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After being informed about the study and potential risks,all patients giving written informed consent will undergo a 1-week screening period to eligibility for study entry.At week 0,patients who meet the eligibility requirements will be randomized into two groups(experimental group and control group)in a 1:1 ratio to Tangningtongluo tablets(4 tablets,tid,po.) or Calcium dobesilate capsules(1 capsule,tid,po.).

Official Title
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Clinical Study on the Efficacy and Safety of Tangningtongluo Tablet in Treating Non Proliferative Diabetic Retinopathy - The Syndrome of Yin Asthenia Generating Intrinsic Heat and Eye Collateral Stasis

Conditions
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Type2 Diabetes, Diabetic Retinopathy

Intervention / Treatment
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* Drug: Tangningtongluo tablets
* Drug: Calcium dobesilate capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients with the diagnosis of type 2 diabetes. 2. Patients with the diagnosis of non-proliferative diabetic retinopathy and the classified as mild and moderate. 3. Target eye best corrected vision acuity (BCVA) ≥ 34 points (ETDRS vision chart, vision equivalent of score 20 / 200, decimal 0.1). 4. Patients who meet the syndrome differentiation standards of yin asthenia generating intrinsic heat and eye collateral stasis in traditional Chinese medicine. 5. HbA1C ≤ 9%. 6. Age between 18 and 75 years old 7. Informed consent, voluntary subject. The process of obtaining informed consent form complies with Good Clinical Practice(GCP). Exclusion Criteria: 1. Patient with the diagnosis of diabetic retinopathy is combined with severe vitreous blood effusion, or required total retinal laser treatment or vitrectomy. 2. Patient who has been treated with full retinal laser photocoagulation. 3. Patient with difficulty in evaluating fundus images with refractive medium turbidity. 4. Patient was diagnosed of acute metabolic disorders such as diabetic ketoacidosis or combined with severe acute infection in the past 1 month. 5. Patient with other serious diabetes complications, such as diabetes gangrene. 6. Patient was allergic to Tangningtongluo tablets, or Calcium dobesilate, or its composition. 7. Female patient with pregnancy, or prepare for pregnancy, or lactating. 8. Patient with serious cardiovascular, liver, kidney or hematopoietic system disease, and mental diseases. 9. Liver and renal function (Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) above 2 x Upper limit of normal (ULN)and Cr> above 1 x Upper limit of normal (ULN)). The diabetic nephropathy stage was 4 and above. 10. Patient with eye diseases such as glaucoma, uveitis, optic neuropathy, and severe cataract. 11. Patient participated in other clinical researches within a month.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tangningtongluo tablets<br>Tangningtongluo tablets, 4 tablets one time,tid,po, taken after meals.The patients will receive drugs for 24 weeks continuously. After 24 weeks, the researchers will decide whether to continue depend on the patient condition and willingness. The maximum medication time is up to 48 weeks.Basic treatment: According to the comprehensive objectives of China Type 2 Diabetes Guidelines (2020 Edition) .The Angiotensin-Converting Enzyme（ACEI） and Angiotensin Receptor Blocker（ARB） drugs will be continued to use as the original treatment protocol. | Drug: Tangningtongluo tablets<br>* Four pills each time and three times a day after meals.<br>|
| Active Comparator: Calcium dobesilate capsules<br>Calcium dobesilate capsules, 1 capsule at a time, tid,po.(morning, midday, and evening), used on an empty stomach.After 24 weeks, the researchers will decide whether to continue depend on the patient condition and willingness. The maximum medication time is up to 48 weeks.Basic treatment: According to the comprehensive objectives of China Type 2 Diabetes Guidelines (2020 Edition) .The Angiotensin-Converting Enzyme（ACEI ）and Angiotensin Receptor Blocker （ARB） drugs will be continued to use as the original treatment protocol. | Drug: Calcium dobesilate capsules<br>* 1 capsule at a time, tid,po.(morning, midday, and evening), used on an empty stomach.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best corrected vision acuity (BCVA) | using ETDRS vision chart measure vision change from Baseline | At 24 weeks | 
| diabetic retinopathy(DR)progression rate | Using ETDRS Classification to evaluate DR Progress rate | At 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fundus photography | quantitative analysis of fundus microhemangioma, bleeding, exudation, and tube diameter. | At 12, 24weeks | 
| Retinal blood oxygen saturation | measure retinal blood oxygen saturation | At 12, 24weeks | 
| Retinal macular optical coherence tomography angiography (OCTA) | measure macular vascular density, retinal thickness, retinal volume; | At 12, 24weeks | 
| HbA1c | Measure the patient's HbA1c | At 12,24,36 and 48 weeks | 
| Routine eye examination; | Including the examination of cornea, lens, anterior chamber, iris, etc | At 4,8,12, 24,36 and 48 weeks | 
| Efficacy of traditional Chinese medicine syndrome. | It includes the evaluation of the main symptoms such as blurred vision, dry eyes, secondary symptoms such as mental fatigue, shortness of breath and lazy speech, dry mouth and dry throat and etc. | At 12, 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Retinopathy, Tangningtongluo tablets