Contact information
Type
Scientific
Primary contact
Prof H P Sauerwein
ORCID ID
Contact details
Academic Medical Centre (AMC)
Department of Endocrinology and Metabolism
F5-170
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 3061
h.p.sauerwein@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
Insulin sensitivity is already reduced at birth in preterm Small-for-Gestational-Age (SGA) infants, compared to preterm Appropriate-for-Gestational-Age (AGA) infants.
Ethics approval
Approval received from the Central Committee on Research inv. Human Subjects on the 30th January 2006 (ref: P05.1488C).
Study design
Observational study
Primary study design
Observational
Secondary study design
Multi-centre
Trial setting
Not specified
Trial type
Other
Patient information sheet
Condition
Small for gestational age, prematurity, insulin sensitivity
Intervention
Methods used:
1. Glucose concentration: this will be measured with the glucose oxidase method using a Beckman Glucose Analyzer 2 (Beckman, Fullerton, CA)
2. Insulin: this will be determined with a chemiluminescent immunometric assay (Immulite 2000, Diagnostic Products Corporation, Los Angeles, USA)
3. Free Fatty Acid (FFA) concentration: this will be determined with an enzymatic colorimetric method (NEFA-C test kit, Wako Chemicals GmbH, Neuss, Germany)
4. Cortisol: this will be determined with a chemiluminiscent immunoassay (Immulite 2000, Diagnostic Products Corporation, Los Angeles, USA)
5. Adiponectin: this will be determined by a radioimmunoassay (Linco, St. Charles, USA)
6. Stable isotope measurements: Newborns are infused with [U-13C] glucose and [2-13C] glycerol. Isotope dilution and label incorporation will be determined by gas chromatography mass spectrometry (GCMS) and mass isotopomer distribution analysis (MIDA) in glucose, isolated from plasma
Calculations:
1. Rate of appearance (Ra) of glucose during steady state is calculated by the isotope dilution technique from the [U-13C] enrichment of glucose, using calculations for steady state kinetics, adapted for the use of stable isotopes: Ra = (Ei/Ep) × I, where Ei and Ep are the enrichments of infusate and plasma respectively, and I is the infusion rate of [U-13C] glucose
2. Rate of disappearance (Rd): rate of exogenous glucose infusion plus the rate of endogenous glucose production
3. Endogenous glucose production: Rate of appearance minus rate of exogenous glucose infusion
4. Absolute gluconeogenesis: fractional gluconeogenesis (measured by MIDA) times rate of appearance
5. Glycogenolysis: Endogenous glucose production minus absolute gluconeogenesis
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
Rate of appearance and disappearance of glucose during insulin infusion
Secondary outcome measures
1. Rate of gluconeogenesis and glycogenolysis
2. Plasma Free Fatty Acid (FFA) concentrations
3. Plasma concentrations of insulin, cortisol and adiponectin
Overall trial start date
01/04/2007
Overall trial end date
01/04/2008
Reason abandoned
Eligibility
Participant inclusion criteria
1. Premature infants 28 to 32 weeks gestational age
2. Presence of a (central) venous and arterial catheter for clinical reasons
3. For preterm SGA infants: growth retardation caused by placental insufficiency, assessed by maternal history (pregnancy induced hypertension, preeclampsia), and confirmed by Doppler flow measurements of the umbilical arteries (Pulsatility Index [PI] more than +2 Standard Deviation [SD] for gestational age, measured on two occasions)
Participant type
Patient
Age group
Neonate
Gender
Not Specified
Target number of participants
16
Participant exclusion criteria
1. For preterm SGA infants: growth retardation based on other causes (e.g. congenital infections, congenital malformations)
2. Major congenital malformations
3. Severe perinatal asphyxia defined as five minute Apgar score less than seven
4. Severe disturbances of glucose metabolism (glucose intake less than 4 or more than 8 mg.kg-1.min-1, or need for insulin therapy to maintain the glucose concentration between 2.6 and 8 mmol/l)
5. Severe respiratory distress. Mild ventilatory support is allowed:
a. nasal Continuous Positive Airway Pressure (nCPAP) with maximum Fraction of Inspired Oxygen (FiO2) of 0.40, maximum Positive End Expiratory Pressure (PEEP) 6 cm Water (H2O)
b. Synchronised Intermittent Mandatory Ventilation (SIMV) with maximum inspiratory peak pressure of 18 cm H2O and maximum FiO2 of 0.40
c. High Frequency Oscillatory Ventilation (HFOV) with maximum continuous distending pressure of 12 cm H2O and maximum FiO2 of 0.30
6. Need of vasopressor support for hypotension
7. Treatment with systemic corticosteroids
8. Clinical or laboratory evidence of sepsis: lethargy or irritability, hypo- or hyperthermia, temperature instability, tachypnea, apnea, bradycardia, hypotension, gastric retention, abdominal distension, pallor, elevated C- Reactive Protein (CRP)-level, leukocytosis or leukocytopenia and increased number of band neutrophils
9. Low haemoglobin level at the study days with need for a blood transfusion
10. Positive family history for type two diabetes in first degree relatives
11. No informed consent from parents or legal guardians
Recruitment start date
01/04/2007
Recruitment end date
01/04/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academic Medical Centre (AMC)
Amsterdam
1100 DD
Netherlands
Sponsor information
Organisation
Diabetes Fonds Nederland (The Netherlands)
Sponsor details
Stationsplein 139
Amersfoort
3818 LE
Netherlands
info@diabetesfonds.nl
Sponsor type
Research organisation
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Academic Medical Centre (AMC) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary