The Therapeutic Effects of Insulin and Berberine on Stress Hyperglycemia

Study Overview
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Brief Summary
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Berberine is a conventional component in Chinese medicine. In recent years, effects of Berberine on improvement of glucose metabolism have been explored. The purpose of this study is to observe the therapeutic effects of combination of insulin and berberine on stress hyperglycemia in patients after cardiac surgery.

Detailed Description
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Patients at risk for stress hyperglycemia are often prescribed insulin (Intensive insulin therapy, IIT and maintenance of blood glucose at a level between 80 and 110 mg per deciliter), which are the medication that reduce the level of glucose in the blood. By lowering the glucose level, these patients have a lower incidence of arrhythmia, myocardial ischemia and reperfusion injury, and heart failure and so on. But there are many patients whose hyperglycemia are not well controlled.If investigators are simply doubling the insulin, that only 10% of the benefit can be received.And it often bring significant side effects (Such as: hypoglycemia, etc.) in critically ill patients. Several studies have suggested that the use of berberine can effectively lowering the blood glucose level.The chemical structure and mechanisms of drug is clearly, and the side effects are seldom, the price of berberine is very cheap. The purpose of this study is to observe the therapeutic effects of combination of insulin and berberine on stress hyperglycemia in patients with heart disease whose level of blood glucose are not well controlled when only using insulin postoperatively. This study will enroll postoperative patients who currently are injected with insulin by insulin pump，but the level of blood glucose is not controlled well. Patients will be assigned to receive 500mg of Berberine twice a day or a placebo(meanwhile they are receiving intensive insulin therapy) in a randomized, double blind, and prospective way. Investigators will occur at preoperative baseline, operating time and postoperative days 2, 4 and 8. Blood will be collected for laboratory testing, and acute physiology and chronic health evaluationⅡ and therapeutic intervention scoring system-28 will assess patient's condition at baseline and days 2, 4 and 8. At days 2, 4 and 8, medication efficacy will be also assessed and tests of blood glucose will be performed. Insulin count will be used to assess effectiveness of Berberine treatment at days 2, 4 and 8. Meanwhile, medication side effects will be monitored and the incidence of hypoglycemia or stool frequency are rigorously recorded at days 2, 4 and 8.

Official Title
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The Therapeutic Effects of Combination of Insulin With Berberine on the Patients With Stess Hyperlipemia:a Prospective, Double Blind, Randomized, Placebo-controlled, Single-center Clinical Trial

Conditions
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Hyperglycemia

Intervention / Treatment
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* Drug: Berberine; Insulin
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of stress hyperglycemia (fasting glucose >6.9 mmol/L or random glucose >11.1 mmol/L without evidence of previous diabetes); Worsening glycemic control; Individuals who had cardiac surgery before recruitment; Those who voluntarily sign the consent form after being fully informed and understanding the purpose and procedures of the study, characters of the disease, effect of medications, methods of related examinations, and potential risk/benefits of the study; Exclusion Criteria: Individuals with a history of diabetes; Individuals who are not able to cooperate; Female of childbearing potential; Severe liver or renal disease, or cancer history; Individuals who are involved in designing, planning or performing this clinical trial; Individuals with any condition that could be worsened by supplemental Berberine; Individuals with severe gastrointestinal disease; Individuals with infectious diseases; Current participation in another clinical trial;
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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berberine; Insulin<br>Follow the previous administration program，participants will continue to receive intensive insulin therapy; Besides injecting insulin, participants will receive 500mg berberine twice a day for 8 days. Drug: Berberine; Insulin | Drug: Berberine; Insulin<br>* Participants will receive 500mg Berberine twice a day for 8 days; Meanwhile，participants will also continue to receive intensive insulin therapy.<br>* Other names: No other name;|
| Active Comparator: Insulin<br>Besides receiving intensive insulin therapy, participants will take a placebo twice a day for 8 days. Drug: Insulin | Drug: Insulin<br>* Participants will continue to receive intensive insulin therapy; Meanwhile, Participants will also receive a placebo twice a day for 8 days.<br>* Other names: No other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of effects of insulin and berberine on stress hyperglycemia | Levels of blood glucose will be used to evaluate the hypoglycemic activity of berberine (Blood glucose is measured every 4 hours, and when patient's blood glucose are not stable, blood glucose can be measured every 1 hours.). | Within the first 10 days (plus or minus 3 days) after cardiac surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Synergy of insulin and berberine on stress hyperglycemia | Total dose of insulin (If there is synergy between insulin and berberine, the total dose of insulin should be reduced.) | Within the first 10 days (plus or minus 3 days) after cardiac surgery | 
| Mechanism of berberine on stress hyperglycemia | Hyperinsulinaemic-euglycaemic clamp will be used to assess the improvement in insulin resistance and initially explore the mechanism of berberine hypoglycemic. | Within the first 10 days (plus or minus 3 days) after cardiac surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart disease, Postoperative period, Hyperglycemia, Berberine, Insulin, Clinical trials as topic