Contact information
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
S51644
Study information
Scientific title
In vivo analysis of the 11-beta-hydroxysteroid dehydrogenase activity during acute and prolonged critical illness using isotopically labeled cortisol and cortisone: an observational study
Acronym
Study hypothesis
Current hypothesis as of 15/02/2012
Cortisol levels remain high in critically ill patients, in spite of low adrenocorticotrophic hormone (ACTH) levels. We hypothesize that hypercortisolism during critical illness is driven mainly by a reduced cortisol metabolism.
Previous hypothesis
Cortisol levels remain high in prolonged critically ill patients, in spite of low adrenocorticotrophic hormone (ACTH) levels. We hypothesize that hypercortisolism during acute critical illness is driven mainly by the hypothalamic-pituitary-adrenal (HPA) axis, whereas during prolonged critical illness regeneration of cortisol in the peripheral tissues in an ACTH-independent way via 11beta-hydroxysteroid dehydrogenase (HSD) becomes predominant.
As of 15/02/2012, the following changes were made to the record.
Public title: Updated from In vivo analysis of the 11-beta-hydroxysteroid dehydrogenase activity during acute and prolonged critical illness using isotopically labeled cortisol and cortisone to In vivo analysis of the 11-beta-hydroxysteroid dehydrogenase activity during critical illness using isotopically labeled cortisol and cortisone
Anticipated start date was updated from 01/01/2010 to 13/02/2012.
Anticipated end date was updated from 31/12/2010 to 01/06/2012.
Ethics approval
Institutional Review Board of the Catholic University Leuven School of Medicine approved on the 21st September 2009 (ref: B32220096943)
Adaptations to the original protocol are approved on the 27th of January 2012.
Study design
Observational case-control study
Primary study design
Observational
Secondary study design
Case-control study
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Critical illness
Intervention
Current interventions as of 15/02/2012
After admission to the SICU, patients will be evaluated on their appropriateness for the study and written informed consent will be obtained from the patient or the closest family member or legal guardian.
11-beta-reductase activity will be assessed by infusion of a deuterated cortisol tracer (D4-cortisol). This is a non-radioactive labelled form of cortisol, the bodys own natural steroid hormone. In addition, a deuterated cortisone tracer (D2-cortisone) will be infused at the same time to obtain information on the directionality of the 11-beta-hydroxysteroid dehydrogenase activity.
Infusion of D4-cortisol/D2-cortisone will occur according to the following schedule:
- 9,11,12,12-D4-cortisol as a bolus of 0.7 mg followed by infusion of 0.35 mg/hour; blood samples are taken at t = -5, +60, +120, +160, +165, +170, +175 min.
- 1,2-D2-cortisone as a bolus of 0.076 mg at t = +100 followed by infusion of 0.1053 mg/hour; an additional blood sample is taken at t = -5 min, +120min,+140 min.
- urine samples are collected at t =0, +60, +120, +180.
- A complete 24h urine collection will be collected started at the moment of study.
For patients, blood and urine samples are taken via the catheters that are present.
Control persons will receive two intravenous catheters for the collection of blood samples; for collection of the urine samples they will be asked to urinate at the appropriate time points.
Previous interventions
After admission to the SICU, patients will be evaluated on their appropriateness for the study and written informed consent will be obtained from the patient or the closest family member or legal guardian.
11-beta-reductase activity will be assessed by infusion of a deuterated cortisol tracer (D4-cortisol). This is a non-radioactive labelled form of cortisol, the bodys own natural steroid hormone. In addition, a deuterated cortisone tracer (D2-cortisone) will be infused at the same time to obtain information on the directionality of the 11-beta-hydroxysteroid dehydrogenase activity.
Infusion of D4-cortisol/D2-cortisone will occur according to the following schedule:
- 9,11,12,12-D4-cortisol as a bolus of 0.7 mg followed by infusion of 0.35 mg/hour; blood samples are taken at t = -5, +60, +120, +160, +165, +170, +175 min.
- g 1,2-D2-cortisone as a bolus of 0.076 mg at t = +120 followed by infusion of 0.1053 mg/hour; an additional blood sample is taken at t = +140 min.
- urine samples are collected at t =0, +60, +120, +180.
For patients, blood and urine samples are taken via the catheters that are present.
Control persons will receive an arterial catheter for the collection of blood samples; for collection of the urine samples they will be asked to urinate at the appropriate time points.
Both patients and control persons will receive an extra intravenous catheter for infusion of the tracers.
In addition to the tracer injection, daily blood samples (4 ml) will be taken from all included patients for characterisation of the HPA axis during critical illness.
Intervention type
Drug
Phase
Not Applicable
Drug names
Cortisol, cortisone
Primary outcome measure
Current primary outcome(s) as of 15/02/2012
An estimation of the amount of ACTH-driven cortisol production , the amount of cortisol regenerated from cortisone via 11-beta-HSD1and 2 and the activity of the different metabolizing enzymes based on urinary metabolites.
Previous primary outcome(s)
An estimation of the amount of ACTH-driven cortisol production and the amount of cortisol regenerated from cortisone via 11-beta-HSD1, measured at day 2 and 7 after admission.
Secondary outcome measures
No secondary outcome measures
Overall trial start date
13/02/2012
Overall trial end date
01/06/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 15/02/2012
For patients:
1. Admitted to the surgical intensive care unit (SICU) of the Leuven University Hospital
2. No age limits, either sex
For healthy control persons:
1. Age- and gender-matched to the included patients
Previous inclusion criteria
For patients:
1. Admitted to the surgical intensive care unit (SICU) of the Leuven University Hospital
2. Estimated duration of illness prior to admission less than 48 hours
3. No age limits, either sex
For healthy control persons:
1. Age- and gender-matched to the included patients
Participant type
Patient
Age group
Other
Gender
Both
Target number of participants
A first sample comprising 11 patients and 11 control persons; to be increased as appropriate
Participant exclusion criteria
Steroids received during the last 3 months
Recruitment start date
13/02/2012
Recruitment end date
01/06/2012
Locations
Countries of recruitment
Belgium
Trial participating centre
Director of the Department of Intensive Care Medicine
Leuven
3000
Belgium
Sponsor information
Funders
Funder type
Government
Funder name
Methusalem (Belgium) - long term structural funding by the Flemish Government
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
Basic results (scientific)
Publication list
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23506003
Publication citations
-
Results
Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Berghe G, Reduced cortisol metabolism during critical illness., N. Engl. J. Med., 2013, 368, 16, 1477-1488, doi: 10.1056/NEJMoa1214969.