|- candidate number||15321|
|- NTR Number||NTR4153|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||27-aug-2013|
|- Secondary IDs||39302.042.11 ABR|
|- Public Title||CALIFORNIA trial|
|- Scientific Title||Calprotectin, intestinal Fatty Acid Binding Protein, oral feeding, Near Infrared Spectroscopy and bile acids as possible prognostic factors for development of necrotising enterocolitis in high risk neonates|
|- ACRONYM||CALIFORNIA trial|
|- hypothesis||We hypothesize that before clinical manifestation of NEC, urine I-FABP, serum GLP1/2, faecal Calprotectin, faecal TLR4 (on shedded enterocytes) and faecal bile acids can be used as predictive markers for NEC.
We also hypothesize that Near Infrared Spectroscopy is able to identify neonates at high risk for NEC by early identification of decreased bowel oxygenation.
Finally we hypothesize that the faecal microbiota is different in high risk neonates who develop NEC versus those who do not. |
|- Healt Condition(s) or Problem(s) studied||Necrotizing enterocolitis, Biomarkers, Gut wall integrity, Bile acid metabolism, Near-infrared fluorescence imaging|
|- Inclusion criteria||All children admitted to the neonatology department, which are|
- born at a gestational age of <30 weeks or
- born with a birth weight of <1000 gram or
- born at a gestational age of <32 weeks and categorized as small for gestational age (birth-weight ¡Ü 1200 gram) or
- born with a cardiovascular disease resulting in a possibly reduced splanchnic bloodflow (e.g. aortic coarcation, heart disease with ductal dependent systemic circulation) or
- antenatal exposed to NSAIDs (after maternal tocolysis with Indomethacine)
|- Exclusion criteria||Other abdominal diseases, e.g. abdominal wall defects or congenital intestinal atresias|
|- mec approval received||yes|
|- multicenter trial||no|
|- control||Not applicable|
|- Type||Single arm|
|- planned startdate ||5-okt-2012|
|- planned closingdate||5-okt-2014|
|- Target number of participants||0|
|- Primary outcome||The development of necrotising enterocolitis as determined by an independent paediatric radiologist (pneumatosis intestinalis on abdominal x-ray) or by surgeon during surgery|
|- Secondary outcome||Urinary i-FABP/creatinin ratio, urinary 8-OHdG/creatinine ratio, urinary F2-IsoP/creatinin ratio, faecal Calprotectin and faecal bile acids, gene-expression (ao.TLR-4) on shedded enterocytes in the faeces, GLP1/2 in plasma, bile-acids in plasma, and regional tissue oxygenation measured by abdominal/cerebral NIRS.|
|- Timepoints||Collection/measurement Day
(until development of abdominal emergency
until NICU discharge
(with a maximum of 5 weeks))
Urine collection Day 1 postnatal afterwards three times a week
Faeces collection Day 1 postnatal afterwards two times a week
Blood collection - within first 7days post-natal
- Cerebral and abdominal NIRS measurement Day 1 up to and including day 5 postnatal, day 8 + weekly
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD, PhD JBF Hulscher|
|- CONTACT for SCIENTIFIC QUERIES||MD, PhD JBF Hulscher|
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|University Medical Center Groningen (UMCG)|
|- Brief summary||Rationale: Necrotizing enterocolitis (NEC) is the most frequent, often life threatening, gastrointestinal disease in neonates. Mortality can reach 40%, and both short and long term morbidity are significant. Its cause is yet unknown. The risk of developing NEC is inversely related to gestational age and birth weight. Other risk factors for NEC are cardiovascular disorders associated with decreased intestinal circulation and maternal tocolysis with NSAIDs. However, it is not possible yet to identify neonates who will ultimately develop NEC. Identification of these patients is the key in both prevention and early treatment of NEC.
Objective: To identify non-invasive markers for NEC in neonates at risk to develop this disease.
Study design: prospective cohort study
Study population: 100 consecutive neonates considered to have risk factors for NEC, i.e. gestational age ¡Ü 30 weeks, birth weight ¡Ü 1000 gram, gestational age ¡Ü 32 weeks and birth weight ¡Ü 1200 gram, antenatal exposure to NSAIDs, cardiovascular disorders associated with decreased intestinal circulation.
Intervention (if applicable): There are no interventions
Main study parameters/endpoints:
Study parameters: urinary Intestinal Fatty Acid Binding Protein (I-FABP) to Creatinine ratio, urinary 8-hydroxy-2¡¯-deoxyguanosine (8-OHdG) to creatinine ratio, urinary F2-isoprostanes (F2-IsoPs) to creatinine ratio, faecal Calprotectin, faecal bile acids, faecal microbial analysis, genexpression (e.g. TLR-4 on shedded enterocytes in the faeces), plasma levels of Glucagon Like Peptide-1,2 and bile acids, Near Infrared Spectroscopy (NIRS) of abdomen and cerebrum.
Endpoint: the development of NEC as demonstrated radiologically (defined as the presence of pneumatosis intestinalis on an abdominal X-ray, diagnosed by an independent paediatric radiologist) or diagnosed during surgery.
|- Main changes (audit trail)|
|- RECORD||27-aug-2013 - 12-okt-2013|