Methionine Metabolism in Enterally Fed Pediatric Sepsis

Methionine Metabolism in Enterally Fed Critically Ill Children

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 muscle and structural protein synthesis is decreased. The metabolism of sulfur amino acids through the splanchnic area and specifically methionine and cysteine have not been investigated in critically ill septic children, despite that sulfur amino acids have important roles in thiol, antioxidant and epigenetic reactions. Methionine metabolism in sick children will be influenced by its rate of utilization through different pathways. Our study aims to investigate the metabolism of methionine and cysteine when both amino acids are given by the enteral route in critically ill septic children. The investigators are focused on the rates of transmethylation, remethylation and transsulfuration in critically ill septic children, and if the current standard nutrition maintains methionine nutritional balance and functional requirements in critically ill children fed by the enteral route.

Study Overview

• Status: Completed
• Conditions: Sepsis; Critical Illness
• Intervention / Treatment: Other: Observational

Detailed Description

This is a prospective, translational study on the splanchnic metabolism of methionine to determine the rates of the different pathways and synthesis rates of glutathione when critically ill children are fed by the enteral route, and the difference among various age groups. 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), males 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 15 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 Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 19 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Septic pediatric patients: A total of 45 critically ill children age 1 month-19 years with diagnosis of sepsis, as defined by the International Sepsis Consensus Conference.

Description

Inclusion Criteria:

1. Children 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 4.0 kg
4. Need for enteral nutrition by a nasogastric/nasoduodenal tube
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 unable to tolerate enteral feedings
6. Weight less than 4.0 kg

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critically Ill Pediatric Patients; Critically ill septic pediatric patients, Age 1 month-3 years, Age 4-12 years and Age 13-19 years, males and females	Other: Observational; Observational, Translational non-treatment study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methionine Metabolism	Rates of transmethylation, remethylation and transsulfuration and erythrocyte GSH synthesis when nutrients are given by the enteral route in pediatric critically ill patients.	Clinical Signs, AEs, SAEs, CO2, Tracer Infusion, Blood: (Baseline - 8 hours)

Collaborators and Investigators

• Sponsor: The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): October 1, 2016
• Study Completion (ACTUAL): October 1, 2016

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: June 21, 2013
• First Posted (ESTIMATE): June 28, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Pediatric; Pediatrics; Observational Study; Sepsis; Enteral Nutrition; Methionine Metabolism
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Critical Illness
• Other Study ID Numbers: STU-042011-088