Methionine Metabolism in Parenterally Fed Pediatric Sepsis

Sepsis Clinical Trial

Official title:

Methionine Metabolism in Parenterally Fed Critically Ill Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01891682
• Other study ID #: STU-022012-035
• Status: Completed
• Phase: N/A
• First received: June 24, 2013
• Last updated: March 20, 2017
• Start date: October 2012
• Est. completion date: October 2016

Study information

• Verified date: March 2017
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Critically ill children have abnormal utilization of nutrients such as glucose, lipids and protein. Protein synthesis is increased mainly in the form of immune and signaling proteins, while synthesis of muscle and structural proteins is decreased. The metabolism of sulfur amino acids and specifically methionine and cysteine have not been investigated in critically ill septic children, despite that sulfur amino acids have important roles on thiol, antioxidant and epigenetic reactions, as well as precursor of glutathione (GSH). Methionine metabolism in critically ill children will be influenced by its rate of utilization through the transmethylation, remethylation and transsulfuration pathways, which are the major pathways of methionine metabolism.

The investigators study aims to investigate the metabolism of methionine and cysteine in parenterally fed critically ill septic children. The investigators aim to determine the rates of transmethylation, remethylation, transsulfuration and GSH synthesis rates in critically ill septic children, to determine in vivo, whole body sulfur amino acid metabolism when sulfur amino acids are supplied by the parenteral route. The objective is to determine whether current parenteral intakes support GSH synthesis and if methionine metabolism differs when supplied by the parenteral versus the enteral route. Methionine parenteral requirements will be also studied by using the indicator amino acid oxidation and balance technique.

Description:

This is a prospective, translational study on whole body methionine metabolism and requirements when administered by the parenteral route in critically ill septic children. The study size will include 45 critically ill septic, pediatric patients (15 infants at 1 month-3 years of age, 15 children at 4-12 years of age and 15 adolescent at 13-19 years of age, male and females admitted to the pediatric intensive care unit (PICU) at Children's Medical Center, Dallas. The minimal subject's weight will be 4 kg. The number of subjects includes an expected drop out rate of about 20%, in order to obtain 12 patients with complete data in each group. Patients will receive nutritional support as per standard care. This study will yield important knowledge and may lead in the future to changes in the current practice on the management of critically ill pediatric patients in the PICU.

Study Aim#1: Determine the parenteral requirements of methionine, in the presence of cysteine, in critically ill septic patients' required extended use of TPN, by using the indicator amino acid oxidation and balance technique.

Study Aim#2: Determine methionine metabolism through the rates of transmethylation, transsulfuration and remethylation at the current standard intakes of methionine of 120 mg.kg.d. with negligible amounts of cysteine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 19 Years

Eligibility

Inclusion Criteria:

1. Age 1 month-19 years

2. Diagnosis of severe sepsis diagnosed as clinical sepsis syndrome (requires two of the following criteria):

• Source of infection

• Fever or Hypothermia

• Leukocytosis or Leucopenia

• Poor organ perfusion (such as delayed capillary refill or decreased urine output or hypotension)

• Bacteremic sepsis demonstrated by positive blood culture

3. Weight greater or equal to 4 kg

4. Need for parenteral nutrition

5. Presence of central and/or arterial venous access as per clinical indication

Exclusion Criteria:

1. Patients with metabolic diseases (i.e. Insulin dependent diabetes mellitus, urea cycle disorders, cystinuria, etc.)

2. Pregnancy

3. Primary liver failure

4. Primary renal failure

5. Patients on enteral feedings greater than 20% of daily requirement

6. Weight less than 4.0 kg

Related Conditions & MeSH terms

• Critical Illness
• Sepsis

Intervention

Other:
• Observational
Observational, Translational non-treatment study

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parenteral Requirements of Methionine	Breakpoint between the rates of indicator amino acid oxidation and level of parenteral methionine intake.	8 hours
Secondary	Methionine Metabolism	Rates of transmethylation, remethylation and transsulfuration and erythrocyte GSH synthesis when nutrients are given by the parenteral route in pediatric critically ill patients.	8 hours