Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

Coronary Heart Disease Clinical Trial

Official title:

Intravenous Supplementation of Glutamine Preoperatively for Cardiac Function and Recovery Improvement in Adult Accepting Cardiosurgery: A Randomized, Double-Blinded, Placebo-Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01794884
• Other study ID #: glncardio001
• Status: Completed
• Phase: Phase 2
• First received: February 4, 2013
• Last updated: May 27, 2014
• Start date: January 2013
• Est. completion date: March 2014

Study information

• Verified date: May 2014
• Source: Southeast University, China
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

In view of the lack of large-scale clinical study and potent evidence-based medicine, the investigators designed a randomized, double-blind, placebo-controlled study to ascertain whether preoperative intravenous administration with glutamine can improve the postoperative cardiac function and prognosis of adult patients undergoing cardiac surgery. The investigators want to detect the levels of myocardial protein O-GlcNAc modification and HSP70 expression, changes in sensitive indicators of myocardial injury, systemic inflammatory reaction and oxidative stress levels, and to examine the correlation between these changes and Clinical manifestations. The ultimate goal of the study is to explore a new way for clinical myocardial protection.

Description:

Cardiosurgery is mostly done under cardiopulmonary bypass. However, the cardiopulmonary bypass and the later recovery of spontaneous circulation, a cardiac ischemia / reperfusion process, may cause myocardial damage and affect cardiac function as well as prognosis.

Glutamine, an amino acid abundant in the human body, plays an important role in the regulation of metabolism and immune cells and the protection of organs. Relative lack of glutamine is reported during stress or serious illness. Animal studies have confirmed that pretreatment with glutamine has a protective effect on the heart, liver, kidney and other organs post ischemia / reperfusion injury. It is also established that glutamine exerts myocardial protection mainly by activating hexosamine biosynthetic pathway, increasing intracellular O-GlcNAc protein modification and expression of heat shock protein 70 (HSP70), starting the protective reaction in the body, improving the function of myocardial cells, and inhibiting the release of inflammatory cytokines and oxidative stress levels. Besides, clinical studies have shown that at the perioperative stage glutamine has a protective effect on cardiac function of the patients treated with pump coronary artery bypass surgery.

The purpose of this study is to ascertain whether preoperative intravenous administration with glutamine (as compared with control group) can improve the postoperative cardiac function and prognosis of adult patients undergoing cardiac surgery and reduce inflammatory response and oxidative stress levels of the body. The correlation between Clinical manifestations and expression of myocardium O-GlcNAc and HSP70 will also be investigated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adult patients with coronary artery disease or rheumatic heart disease accepted cardiosurgery under cardiopulmonary bypass

Exclusion Criteria:

• ejection fraction(EF)<50%

• Preoperative support with intra-aortic balloon pump(IABP)

• Hepatosis

• Renal dysfunction

• Myocardial infarction attack within 3 months

• Emergency operation

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia
• Rheumatic Heart Disease

Intervention

Drug:
• Glutamine
20% N(2)-L-alanyl-L-glutamine 0.4g/kg(2ml/kg) mixed with compound amino acid (10ml/kg).Intravenous injection twice (24 hours?1 hour before operation). Injection rate = 6ml/kg/h
• Ringer's solution
Ringer's solution 12ml/kg. Intravenous injection twice (24 hours?1 hour before operation). Injection rate = 6ml/kg/h.

Locations

Country	Name	City	State
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Yuejiang Liu

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	perioperative changes of Cardiac Index (CI)	For each patient,a Swan-Ganz catheter will be inserted after anesthesia induction.CI and other values of hemodynamics will be measured.	postanescesia before surgery, 2, 20 hours after cardiopulmonary bypass (CPB)	No
Secondary	Troponin I(cTnI)	CTnI is a sensitive indicator of myocardial damage.	postanescesia before surgery, 6, 20 hours after CPB	No
Secondary	Brain Natriuretic Peptide (BNP)	BNP is a sensitive indicator of cardiac dysfunction.	postanescesia before surgery, 6, 20 hours after CPB	No
Secondary	Systemic inflammation	Blood levels of Interleukin-6(IL-6)?Tumor Necrosis Factor(TNF-a) and Malondialdehyde (MDA) will be measured.	postanescesia before surgery, 2, 20 hours after CPB	No
Secondary	Heart issue HSP-70	A mass of heart tissue (a part of right auricle of heart,weigh about 50mg) will be cut 20 minutes after CPB for the measurements.	20 minutes after CPB	No
Secondary	Heart issue O-GlcNAc	The same mass of heart tissue described above will be used for the measurements.	20 minutes after CPB	No
Secondary	Recovery index	Recovery index include duration of mechanical ventilation?duration of ICU stay?duration of hospital stay?adverse event and mortality.	Date of surgery until date of hospital discharge (an expected average of 2 weeks)	Yes