The Therapeutic Effects of Insulin and Berberine on Stress Hyperglycemia

Hyperglycemia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02806999
• Other study ID #: HYYuan
• Secondary ID: 20151025
• Status: Not yet recruiting
• Phase: Phase 4
• First received: June 6, 2016
• Last updated: June 16, 2016
• Start date: July 2016
• Est. completion date: July 2017

Study information

• Verified date: June 2016
• Source: Guangdong General Hospital
• Contact: Liming Lei, M.D.
• Phone: 86-18688906579
• Email: anesthlei[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: July 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperglycemia

Intervention

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

Locations

Country	Name	City	State
China	Guangdong Cardiovascular Insititution, Guangdong General Hospital, Guangdong Academy of Medical Science	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong General Hospital

Country where clinical trial is conducted

China, 

References & Publications (11)

Agus MS, Asaro LA, Steil GM, Alexander JL, Silverman M, Wypij D, Gaies MG; SPECS Investigators. Tight glycemic control after pediatric cardiac surgery in high-risk patient populations: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial. Circulation. 2014 Jun 3;129(22):2297-304. doi: 10.1161/CIRCULATIONAHA.113.008124. Epub 2014 Mar 26. — View Citation

Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000 Mar 4;355(9206):773-8. Review. — View Citation

Donner T. Insulin – Pharmacology, Therapeutic Regimens and Principles of Intensive Insulin Therapy. 2015 Oct 12. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer F, Vinik A, Weickert MO, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from http://www.ncbi.nlm.nih.gov/books/NBK278938/ — View Citation

Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009 May 23;373(9677):1798-807. doi: 10.1016/S0140-6736(09)60553-5. Review. — View Citation

Geng FH, Li GH, Zhang X, Zhang P, Dong MQ, Zhao ZJ, Zhang Y, Dong L, Gao F. Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats. Br J Pharmacol. 2016 May;173(10):1569-79. doi: 10.1111/bph.13466. Epub 2016 Apr 5. — View Citation

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006 Aug;55(8):2256-64. — View Citation

Monzillo LU, Hamdy O. Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev. 2003 Dec;61(12):397-412. Review. — View Citation

Rassias AJ. Intraoperative management of hyperglycemia in the cardiac surgical patient. Semin Thorac Cardiovasc Surg. 2006 Winter;18(4):330-8. Review. — View Citation

van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. — View Citation

Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008 Aug 27;300(8):933-44. doi: 10.1001/jama.300.8.933. Erratum in: JAMA. 2009 Mar 4;301(9):936. — View Citation

Zhao GL, Yu LM, Gao WL, Duan WX, Jiang B, Liu XD, Zhang B, Liu ZH, Zhai ME, Jin ZX, Yu SQ, Wang Y. Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress. Acta Pharmacol Sin. 2016 Mar;37(3):354-67. doi: 10.1038/aps.2015.136. Epub 2016 Jan 25. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stool frequency	Evaluating the side effects of Berberine (Causing constipation)	Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	Incidence of hypoglycemia	If the incidence of hypoglycemia is reduced, we will conclude that berberine can reduce the side effects of intensive insulin treatment.	Within the first 10 days (plus or minus 3 days) after cardiac surgery	Yes
Other	Assessment of ventricular function by ultrasound	EF (ejection fraction) value will be measured by ultrasound to assess cardiac function.	Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	Intensive care time		Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	All cause mortality		Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	Assess the severity of the disease by APACHE?	The full name of APACHE? is acute physiology and chronic health ?, a questionnaire is used to acess the severity of the disease.	Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	Assess the nursing workload by TISS-28	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.	Within the first 10 days (plus or minus 3 days) after cardiac surgery	No
Other	Incidence of nosocomial infections	Stress hyperglycemia leads to decreased immunity, and good blood glucose control helps to reduce nosocomial infections.	Within the first 10 days (plus or minus 3 days) after cardiac surgery	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	No

External Links

•   Click here for more information about this study: Therapeutic Effects of Berberine in Patients With Type 2 Diabetes