Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Greet Van den Berghe

ORCID ID

Contact details

Director of the Department of Intensive Care Medicine
Catholic University Leuven University Hospitals
and
Chair of the Division of Acute Medical Sciences
Catholic University Leuven
Herestraat 49
Leuven
3000
Belgium

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 body’s 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 body’s 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 measures

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

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

Organisation

Catholic University Leuven (Katholieke Universiteit Leuven) (Belgium)

Sponsor details

c/o Professor Dr Ir Koenraad Debackere
Managing Director
Leuven Research and Development
Minderbroedersstraat 8A - bus 5105
Leuven
3000
Belgium

Sponsor type

University/education

Website

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

Results - basic reporting

Publication summary

2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23506003

Publication citations

  1. 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.

Editorial Notes