Cysteine Supplementation in Critically Ill Neonates

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by University of California, Los Angeles.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00254176
First received: November 14, 2005
Last updated: February 25, 2010
Last verified: February 2010
  Purpose

Critically ill babies less than 1 month of age have deficient amounts of the antioxidant glutathione and a high incidence of disease associated with oxidative injury compared to healthy babies. These diseases include but are not limited to damage to the eyes, lungs, and intestines. Frequently becoming chronic and potentially life threatening, these diseases result in a significantly decreased quality of life to the infant along with increased costs to the infant's family and society.

The amino acid cysteine comprises a third of the tripeptide glutathione and directly influences glutathione production. Older children ill with infection and stable, premature neonates administered cysteine supplementation to their diet have been previously shown to increase their glutathione production and concentrations. Furthermore, cysteine supplementation in the ill children resulted in a quicker resolution of their illness.

Although most critically ill babies require IV nutrition (i.e., TPN) before and during their illness, commercially available TPN does not include cysteine as a significant nutrient. Cysteine has effectively become a safe and standard supplement to routine TPN in a few major hospitals in the U.S.

The purpose of this study is to evaluate the ability of cysteine supplementation to increase glutathione production and concentrations in critically ill babies. Furthermore, the investigators want to evaluate whether cysteine supplementation results in less oxidative tissue injury and ultimately less severe illnesses. The study will enroll babies admitted to the UCLA Medical Center Neonatal Intensive Care Unit (NICU) and they will be chosen at random and in a blinded fashion to receive either cysteine or non-cysteine supplementation to their routine TPN. Small blood samples along with a single 6 hour infusion of a non-radioactive, stable isotope labeled amino acid will be used to measure the production of glutathione as well as other compounds in the blood to give a quantitative assessment to the severity of illness. Clinical information relevant to the babies' illness and subsequent recovery will be recorded.

The results will be compared between cysteine vs. non-cysteine groups and before vs. after individual supplementation. By demonstrating the effect of cysteine supplementation on glutathione production, the incidence and/or severity of disease from oxidative injury in critically ill babies may be decreased if glutathione production is improved.


Condition Intervention Phase
Sepsis
Bronchopulmonary Dysplasia
Necrotizing Enterocolitis
Retinopathy of Prematurity
Systemic Inflammatory Response Syndrome
Dietary Supplement: Parenteral cysteine-HCl supplementation
Dietary Supplement: Placebo - added premasol
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Cysteine Supplementation on Glutathione Production in Critically Ill Neonates

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Total RBC glutathione [ Time Frame: 0 days, 7 days, 60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor necrosis factor (TNF) [ Time Frame: 0 days, 7 days, 60 days ] [ Designated as safety issue: No ]
  • Interleukin-6 (IL-6) [ Time Frame: 0 days, 7 days, 60 days ] [ Designated as safety issue: No ]
  • Oxygen dependency [ Time Frame: through to discharge ] [ Designated as safety issue: No ]
  • Ventilation dependency [ Time Frame: through to discharge ] [ Designated as safety issue: No ]
  • Erythrocyte oxidized:reduced glutathione ratio [ Time Frame: 0 days, 7 days, 60 days ] [ Designated as safety issue: No ]
  • In vivo erythrocyte glutathione synthetic rate [ Time Frame: 7 days, 60 days ] [ Designated as safety issue: No ]
  • Plasma malondialdehyde concentration [ Time Frame: 0 days, 7days, 60 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 108
Study Start Date: September 2006
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cysteine
Subjects that receive cysteine
Dietary Supplement: Parenteral cysteine-HCl supplementation
cysteine-HCl supplementation 121 mg per kg per day
Placebo Comparator: No-cysteine placebo
Subjects that do not receive cysteine but an isonitrogenous placebo
Dietary Supplement: Placebo - added premasol
Premasol 121 mg per kg per day
Other Name: Trophamine

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • mechanically ventilated neonates of all gestational ages and birth weights
  • less than 1 month of postnatal age admitted to the NICU
  • SNAP (Score of Neonatal Acute Physiology) > 10
  • projected requirement for continued parenteral nutrition of at least 1 week duration

Exclusion Criteria:

  • renal or hepatic failure
  • requiring insulin administration
  • requiring extracorporeal life support
  • known inherited metabolic disorders
  • known uniformly fatal congenital anomalies
  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: NCT00254176

Locations
United States, California
UCLA Medical Center, Mattel Childrens Hospital
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Stephen B Shew, M.D. University of California, Los Angeles
  More Information

Additional Information:
Publications:

Responsible Party: Stephen B. Shew, M.D., UCLA School of Medicine
ClinicalTrials.gov Identifier: NCT00254176     History of Changes
Other Study ID Numbers: 04-12-035-05, 5K08-HD052885-04
Study First Received: November 14, 2005
Last Updated: February 25, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Neonate
Glutathione
Cysteine
Sepsis
Stable Isotope

Additional relevant MeSH terms:
Critical Illness
Bronchopulmonary Dysplasia
Enterocolitis
Enterocolitis, Necrotizing
Retinopathy of Prematurity
Systemic Inflammatory Response Syndrome
Disease Attributes
Pathologic Processes
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Retinal Diseases
Eye Diseases
Inflammation
Shock

ClinicalTrials.gov processed this record on September 18, 2014