The Therapeutic Effects of Insulin and Berberine on Stress Hyperglycemia

Sponsor

Guangdong Provincial People's Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02806999

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

16.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperglycemia	Drug: Berberine; Insulin Drug: Insulin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2016

Anticipated Primary Completion Date :

Mar 1, 2017

Anticipated Study Completion Date :

Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Berberine; Insulin 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 Participants will receive 500mg Berberine twice a day for 8 days; Meanwhile，participants will also continue to receive intensive insulin therapy. Other Names: No other name
Active Comparator: Insulin Besides receiving intensive insulin therapy, participants will take a placebo twice a day for 8 days. Drug: Insulin	Drug: Insulin Participants will continue to receive intensive insulin therapy; Meanwhile, Participants will also receive a placebo twice a day for 8 days. Other Names: No other name

Arm

Intervention/Treatment

Experimental: Berberine; Insulin

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

Participants will receive 500mg Berberine twice a day for 8 days; Meanwhile，participants will also continue to receive intensive insulin therapy.

Other Names:

No other name

Active Comparator: Insulin

Besides receiving intensive insulin therapy, participants will take a placebo twice a day for 8 days. Drug: Insulin

Drug: Insulin

Participants will continue to receive intensive insulin therapy; Meanwhile, Participants will also receive a placebo twice a day for 8 days.

Other Names:

No other name

Outcome Measures

Primary Outcome Measures

Evidence of effects of insulin and berberine on stress hyperglycemia [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
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.).

Secondary Outcome Measures

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

Other Outcome Measures

Stool frequency [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
Evaluating the side effects of Berberine (Causing constipation)
Incidence of hypoglycemia [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
If the incidence of hypoglycemia is reduced, we will conclude that berberine can reduce the side effects of intensive insulin treatment.
Assessment of ventricular function by ultrasound [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
EF (ejection fraction) value will be measured by ultrasound to assess cardiac function.
Intensive care time [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
All cause mortality [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
Assess the severity of the disease by APACHEⅡ [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
The full name of APACHEⅡ is acute physiology and chronic health Ⅱ, a questionnaire is used to acess the severity of the disease.
Assess the nursing workload by TISS-28 [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
The full name of TISS-28 is therapeutic intervention scoring system-28. It is a questionnaire used to assess the nursing workload in ICU patients, so TISS-28 can indirectly reflect patient's condition.
Incidence of nosocomial infections [Within the first 10 days (plus or minus 3 days) after cardiac surgery]
Stress hyperglycemia leads to decreased immunity, and good blood glucose control helps to reduce nosocomial infections.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;