In vivo analysis of the 11-beta-hydroxysteroid dehydrogenase activity during critical illness using isotopically labeled cortisol and cortisone
| ISRCTN | ISRCTN08083905 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN08083905 |
| Secondary identifying numbers | S51644 |
- Submission date
- 30/10/2009
- Registration date
- 23/11/2009
- Last edited
- 07/05/2013
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Greet Van den Berghe
Scientific
Scientific
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
Study information
| Study design | Observational case-control study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study objectives | 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(s) | 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. |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 13/02/2012 |
| Completion date | 01/06/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Other |
| Sex | Both |
| Target number of participants | A first sample comprising 11 patients and 11 control persons; to be increased as appropriate |
| Key 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 |
| Key exclusion criteria | Steroids received during the last 3 months |
| Date of first enrolment | 13/02/2012 |
| Date of final enrolment | 01/06/2012 |
Locations
Countries of recruitment
- Belgium
Study participating centre
Director of the Department of Intensive Care Medicine
Leuven
3000
Belgium
3000
Belgium
Sponsor information
Catholic University Leuven (Katholieke Universiteit Leuven) (Belgium)
University/education
University/education
c/o Professor Dr Ir Koenraad Debackere
Managing Director
Leuven Research and Development
Minderbroedersstraat 8A - bus 5105
Leuven
3000
Belgium
"ROR" |
https://ror.org/05f950310 |
|---|
Funders
Funder type
Government
Methusalem (Belgium) - long term structural funding by the Flemish Government
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 18/04/2013 | Yes | No |
