Cysteine Supplementation in Critically Ill Neonates
Recruitment status was: Active, not recruiting
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.
|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 Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||Effect of Cysteine Supplementation on Glutathione Production in Critically Ill Neonates|
- Total RBC glutathione [ Time Frame: 0 days, 7 days, 60 days ]
- Tumor necrosis factor (TNF) [ Time Frame: 0 days, 7 days, 60 days ]
- Interleukin-6 (IL-6) [ Time Frame: 0 days, 7 days, 60 days ]
- Oxygen dependency [ Time Frame: through to discharge ]
- Ventilation dependency [ Time Frame: through to discharge ]
- Erythrocyte oxidized:reduced glutathione ratio [ Time Frame: 0 days, 7 days, 60 days ]
- In vivo erythrocyte glutathione synthetic rate [ Time Frame: 7 days, 60 days ]
- Plasma malondialdehyde concentration [ Time Frame: 0 days, 7days, 60 days ]
|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)|
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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00254176
|United States, California|
|UCLA Medical Center, Mattel Childrens Hospital|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Stephen B Shew, M.D.||University of California, Los Angeles|