Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

Sponsor

Yuejiang Liu (Other)

Overall Status

Completed

CT.gov ID

NCT01794884

Collaborator

(none)

Enrollment

Location

Arms

13.9

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatic Heart Disease Coronary Heart Disease	Drug: Glutamine Drug: Ringer's solution	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glutamine 20% N(2)-L-alanyl-L-glutamine 0.4g/kg(2ml/kg) mixed with compound amino acid (10ml/kg)(volume ratio=1:5).Intravenous injection twice (24 hours、1 hour before operation).	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 Other Names: Dipeptiven (N(2)-L-Alanine L-Glutamine dipeptide)
Placebo Comparator: Ringer's solution Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).	Drug: Ringer's solution Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h.

Arm

Intervention/Treatment

Experimental: Glutamine

20% N(2)-L-alanyl-L-glutamine 0.4g/kg(2ml/kg) mixed with compound amino acid (10ml/kg)(volume ratio=1:5).Intravenous injection twice (24 hours、1 hour before operation).

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

Other Names:

Dipeptiven (N(2)-L-Alanine L-Glutamine dipeptide)

Placebo Comparator: Ringer's solution

Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation).

Drug: Ringer's solution

Ringer's solution 12ml/kg. Intravenous injection twice (24 hours、1 hour before operation). Injection rate = 6ml/kg/h.

Outcome Measures

Primary Outcome Measures

perioperative changes of Cardiac Index (CI) [postanescesia before surgery, 2, 20 hours after cardiopulmonary bypass (CPB)]
For each patient,a Swan-Ganz catheter will be inserted after anesthesia induction.CI and other values of hemodynamics will be measured.

Secondary Outcome Measures

Troponin I(cTnI) [postanescesia before surgery, 6, 20 hours after CPB]
CTnI is a sensitive indicator of myocardial damage.
Brain Natriuretic Peptide (BNP) [postanescesia before surgery, 6, 20 hours after CPB]
BNP is a sensitive indicator of cardiac dysfunction.
Systemic inflammation [postanescesia before surgery, 2, 20 hours after CPB]
Blood levels of Interleukin-6（IL-6）、Tumor Necrosis Factor（TNF-a） and Malondialdehyde (MDA) will be measured.
Heart issue HSP-70 [20 minutes after CPB]
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.
Heart issue O-GlcNAc [20 minutes after CPB]
The same mass of heart tissue described above will be used for the measurements.
Recovery index [Date of surgery until date of hospital discharge (an expected average of 2 weeks)]
Recovery index include duration of mechanical ventilation、duration of ICU stay、duration of hospital stay、adverse event and mortality.