Effect of HMP on Diabetic Microangiopaemia in T2DM

Study Overview
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Brief Summary
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The study mainly investigates the therapeutic effect of Heart-Protecting Musk Pill (HMP) on patients with diabetic microangiopathy. According to the indicators of diabetic nephropathy (DN), diabetic retinopathy (DR), oxidative stress and inflammatory factor in patients with diabetic microvascular disease after using HMP, the investigators aim to evaluate the effect of HMP on diabetic microangiopathy, oxidative stress and inflammation.

Detailed Description
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Diabetes can lead to many diseases as diabetic macrovascular and microvascular complications which result in high disability and mortality rate, thereby seriously affecting the quality of life and life expectancy of diabetic patients. It not only aggravates the family burden of patients, but also becomes the main burden of public health services around the world. Diabetic nephropathy (DN) and diabetic retinopathy (DR) are more serious in diabetic microangiopathy. The glomerulus and retina have the similar tissue structure and physiological function. Therefore, when they are exposured to the same risk factors can lead to microcirculation damage of kidney and retina. DN and DR have similar pathogenesis and development processes. Although the susceptibility genes and cytokines of DN and DR are different, the two can still be predictors of each other and they often coexist in diabetic patients. At present, there are few drugs with definite curative effect on the treatment of diabetic microangiopathy, therefore the treatment of diabetic microangiopathy is an aspect that urgently needs a breakthrough in chronic complications of diabetes. Traditional Chinese medicine has a history of preventing and treating diabetes for thousands of years. For the treatment of chronic complications of diabetes by Chinese medicine, although there are not many Chinese medicines that have obtained curative effects, it has indeed accumulated rich experience in the process of research and clinical treatment that Western medicine could not obtain. Therefore, seeking Chinese medicine to effectively treat diabetic microvascular disease has become a direction worthy of attention and research. Heart-Protecting Musk Pill (HMP) is a commonly used drug in clinical treatment, which comprises seven medicinal substances: Radix Ginseng, Venenum Bufonis, Styrax, Calculus Bovis Artifactus, Cortex Cinnamomi, Borneolum Syntheticum and Artificial Moschus. HMP is a traditional Chinese medicinal compound, which has been effectively used for treating coronary heart disease (CHD) and diabetic macrovascular disease. However, studies on Chinese medicines that are partially similar to HMP have shown that they can improve diabetic retinopathy. Therefore, the study of the efficacy of HMP on diabetic microangiopathy is extremely valuable. Previous researches have shown that HMP owns the effects of reducing oxidative stress, improving inflammation, anti-plateleting aggregation, promoting plasmin activity, and improving hemodynamics. It is possible that HMP can delay or improve the occurrence and development of diabetic microangiopathy through the above effects and even other unclear mechanisms. At present, the drugs used for clinical treatment of type 2 diabetic microangiopathy are limited. Although the pharmacological indications of HMP can be used to deal with the pathogenesis of diabetic microvascular complications, there is still no clinical study of HMP for the treatment of diabetic microvascular complications. Therefore, this study compared the differences in indicators related to diabetic nephropathy, diabetic retinopathy, oxidative stress, and inflammatory factors between the control group and the HMP group before and after treatment to clarify the therapeutic effect of HMP on diabetic microangiopaemia.

Official Title
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Effect of Heart-Protecting Musk Pill on Diabetic Microangiopaemia in Type 2 Diabetes Patients

Conditions
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Diabetes Mellitus, Type 2, Diabetic Angiopathies

Intervention / Treatment
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* Drug: Heart-Protecting Musk Pill
* Drug: Valsartan Capsules
* Drug: Calcium Dobesilate Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Diabetes mellitus Prescribed for Valsartan Capsules and Calcium Dobesilate Capsules Exclusion Criteria: Type 1 diabetes mellitus Secondary diabetes Malignant tumors Active infection Acute diabetic complications Macrovascular complications Mental illness Intellectual disability Impaired heart function Impaired liver function Impaired kidney function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: The type 2 diabetes subjects with diabetic microangiopathy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart-Protecting Musk Pill group<br>Heart-Protecting Musk Pill (pill, 45mg, three times a day, 3 months)+Valsartan Capsules(capsule, 80mg, once a day, 3 months）+Calcium Dobesilate Capsules (capsule, 500mg, three times a day, 3 months) | Drug: Heart-Protecting Musk Pill<br>* Heart-Protecting Musk Pill (pill, 45mg, three times a day, 3 months)<br>* Other names: Heart-Protecting Musk Pill，National Medicine Permission Number Z31020068，86900674000453;Drug: Valsartan Capsules<br>* Valsartan Capsules(capsule, 80mg, once a day, 3 months）<br>* Other names: Valsartan Capsules，National Medicine Permission Number H20040217，86900100000095;Drug: Calcium Dobesilate Capsules<br>* Calcium Dobesilate Capsules(capsule, 500mg, three times a day, 3 months)<br>* Other names: Doxium，H20140641;|
| Placebo Comparator: Control group<br>Valsartan Capsules(capsule, 80mg, once a day, 3 months), Calcium Dobesilate Capsules (capsule, 500mg, three times a day, 3 months) | Drug: Valsartan Capsules<br>* Valsartan Capsules(capsule, 80mg, once a day, 3 months）<br>* Other names: Valsartan Capsules，National Medicine Permission Number H20040217，86900100000095;Drug: Calcium Dobesilate Capsules<br>* Calcium Dobesilate Capsules(capsule, 500mg, three times a day, 3 months)<br>* Other names: Doxium，H20140641;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of biochemical Indicators | Total cholesterol(TC), Triglycerides(TG), High-density lipoprotein cholesterol(HDL-C), Low-density lipoprotein cholesterol(LDL-C), Fasting blood glucose(FBG), Blood urea nitrogen(BUN) | Change from Baseline TC, TG, HDL-C, LDL-C, FBG, BUN at 3 months | 
| Concentration of Glycosylated hemoglobin | Glycosylated hemoglobin(HbA1c) | Change from Baseline HbA1c at 3 months | 
| Concentration of hypersensitive-c-reactive-protein and Cystatin C | hypersensitive-c-reactive-protein(hs-CRP), Cystatin C(CysC) | Change from Baseline hs-CRP and CysC at 3 months | 
| Concentration of Serum creatinine | Serum creatinine(Scr) | Change from Baseline Scr at 3 months | 
| Rate of estimated Glomerular Filtration | estimated Glomerular Filtration Rate(eGFR) | Change from Baseline eGFR at 3 months | 
| Ratio of Urinary albumin to creatinine | Urinary albumin to creatinine Ratio(UACR) | Change from Baseline UACR at 3 months | 
| Concentration of Serum fatty acid binding protein 4 | Serum fatty acid binding protein 4（FABP4) | Change from Baseline FABP4 at 3 months | 
| Indicators of diabetic retinopathy | The vision and fundus photography will be checked by an ophthalmologist to determine the effect. | Change from Baseline effect at 3 months | 
| Concentration of inflammation indicator | Tumor Necrosis Factor-α(TNF-α) | Change from Baseline TNF-α at 3 months | 
| Concentration of inflammation indicator | Vascular Endothelial Growth Factor(VEGF) | Change from Baseline VEGF at 3 months | 
| Concentration of inflammation indicator | CC chemokine ligand 3(CCL3) | Change from Baseline CCL3 at 3 months | 
| Concentration of Oxidative stress indicator | Superoxide dismutase(SOD) | Change from Baseline SOD at 3 months | 
| Concentration of Oxidative stress indicator | Glutathione peroxidase(GSH-Px) | Change from Baseline GSH-Px at 3 months | 
| Concentration of Oxidative stress indicator | Reactive oxygen species(ROS） | Change from Baseline ROS at 3 months | 
| Clinical characteristics | Height, Waistline | Change from Baseline Height, Waistline at 3 months | 
| Clinical characteristic | Weight | Change from Baseline Weight at 3 months | 
| Blood pressure | Systolic Blood Pressure(SBP), Diastolic Blood Pressure(DBP) | Change from Baseline SBP, DBP at 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart-protecting musk pill, type 2 diabetes, diabetic angiopathies