Validity Study of Glutamine to Improve Cardiac Function in Cardiac Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yuejiang Liu, Southeast University, China
ClinicalTrials.gov Identifier:
NCT01794884
First received: February 4, 2013
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Rheumatic Heart Disease
Coronary Heart Disease
Drug: Glutamine
Drug: Ringer's solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Southeast University, China:

Primary Outcome Measures:
  • perioperative changes of Cardiac Index (CI) [ Time Frame: postanescesia before surgery, 2, 20 hours after cardiopulmonary bypass (CPB) ] [ Designated as safety issue: No ]
    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) [ Time Frame: postanescesia before surgery, 6, 20 hours after CPB ] [ Designated as safety issue: No ]
    CTnI is a sensitive indicator of myocardial damage.

  • Brain Natriuretic Peptide (BNP) [ Time Frame: postanescesia before surgery, 6, 20 hours after CPB ] [ Designated as safety issue: No ]
    BNP is a sensitive indicator of cardiac dysfunction.

  • Systemic inflammation [ Time Frame: postanescesia before surgery, 2, 20 hours after CPB ] [ Designated as safety issue: No ]
    Blood levels of Interleukin-6(IL-6)、Tumor Necrosis Factor(TNF-a) and Malondialdehyde (MDA) will be measured.

  • Heart issue HSP-70 [ Time Frame: 20 minutes after CPB ] [ Designated as safety issue: No ]
    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 [ Time Frame: 20 minutes after CPB ] [ Designated as safety issue: No ]
    The same mass of heart tissue described above will be used for the measurements.

  • Recovery index [ Time Frame: Date of surgery until date of hospital discharge (an expected average of 2 weeks) ] [ Designated as safety issue: Yes ]
    Recovery index include duration of mechanical ventilation、duration of ICU stay、duration of hospital stay、adverse event and mortality.


Enrollment: 33
Study Start Date: January 2013
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01794884

Locations
China, Jiangsu
Zhongda Hospital Southeast University
Nanjing, Jiangsu, China, 210009
Sponsors and Collaborators
Yuejiang Liu
  More Information

No publications provided

Responsible Party: Yuejiang Liu, Associate Professor, Southeast University, China
ClinicalTrials.gov Identifier: NCT01794884     History of Changes
Other Study ID Numbers: glncardio001
Study First Received: February 4, 2013
Last Updated: May 27, 2014
Health Authority: China: Ministry of Health

Keywords provided by Southeast University, China:
Glutamine
Cardiosurgery
Cardiopulmonary bypass
Cardiac function
Recovery

Additional relevant MeSH terms:
Rheumatic Fever
Coronary Artery Disease
Coronary Disease
Heart Diseases
Myocardial Ischemia
Rheumatic Heart Disease
Arterial Occlusive Diseases
Arteriosclerosis
Bacterial Infections
Cardiovascular Diseases
Gram-Positive Bacterial Infections
Streptococcal Infections
Vascular Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014