Condition category
Not Applicable
Date applied
04/07/2016
Date assigned
07/07/2016
Last edited
06/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
When we are stressed, the concentration of a hormone called ACTH in the blood rises. This, in turn, increases the amount of stress-hormone cortisol released from the adrenal gland. However, in intensive care unit (ICU) patients this stress response seems to be different. Our research group recently showed that during critical illness high blood levels of cortisol are, to a large extent, due to a decrease in the amount of cortisol broken down in the body, rather than an increase in the amount of the hormone made. These high cortisol levels could in their turn stop the release of ACTH by what is called ‘negative feedback inhibition’. However, it remains unknown whether and to what extent the high cortisol levels in ICU patients evoke feedback-inhibition at certain regions in the brain, and whether and how this effect evolves with the duration of critical illness. As such, documenting a change in ACTH and/or cortisol response to the injection of CRH (another hormone of the brain) over time could be highly informative to understand illness evolution and might open perspectives for new treatment strategies.

Who can participate?
Adult patients (age 18 or over) at the medical and surgical ICU. Healthy individuals are recruited to match with the patient group.

What does the study involve?
Participants are randomly allocated to receive an injection of either CRH or salt water, and blood samples are taken. The next day, each participant receives the other injection, and blood samples are taken again.

What are the possible benefits and risks of participating?
There will be no immediate benefits or risks for participants in the study

Where is the study run from?
Five ICUs of the University Hospitals of Leuven (Belgium)

When is the study starting and how long is it expected to run for?
July 2016 to June 2017

Who is funding the study?
1. Methusalem (long term structural funding by the Flemish Government, Belgium)
2. Research Foundation - Flanders (FWO) (Belgium) to the KU Leuven

Who is the main contact?
Prof. Dr Greet Van den Berghe
greet.vandenberghe@med.kuleuven.be

Trial website

Contact information

Type

Scientific

Primary contact

Prof Greet Van den Berghe

ORCID ID

Contact details

Herestraat 49
Leuven
3000
Belgium
+32 (0)16 34 40 21
greet.vandenberghe@kuleuven.be

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

S58941

Study information

Scientific title

The dynamics of the ACTH and cortisol response to CRH stimulation during critical illness: a randomized, double-blind, placebo-controlled crossover study

Acronym

DACAR

Study hypothesis

We hypothesize that the sustained increased plasma cortisol concentrations during critical illness could exert negative feedback inhibition on the central components of the HPA axis, causing decreased CRH and/or ACTH synthesis and/or release. Such central inhibition might contribute to the observed low plasma ACTH concentrations and the increased incidence of absolute adrenal insufficiency in the prolonged phase of critical illness.

Ethics approval

Ethics Committee (Institutional Review Board) of the University Hospitals Leuven, 23/03/2016, ref: S58941

Study design

Randomized double-blind placebo-controlled crossover study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Critical illness

Intervention

We will study unique patients from different time cohorts, with an increasing duration of critical illness, in order to have three sets of patients who represent three different time points in the course of critical illness. After informed consent, each patient from each cohort will be randomized into two crossover study groups for the order of receiving CRH (test) or placebo injection. Consecutive patients will be randomly assigned to ‘first placebo’ or ‘first CRH’ using blinded envelopes, stratified according to the three ‘time in ICU’ cohorts.

Intervention type

Phase

Drug names

Primary outcome measures

ACTH and cortisol responses to exogenous CRH/placebo in relation with available baseline demographic and clinical outcome data, collected during ICU stay. Quantification of plasma ACTH and cortisol will be done during 2 consecutive mornings from 10.45-13.00h, after receiving an alternate injection of CRH or placebo each morning, in the acute phase (ICU day 3-6), the intermediate phase (ICU day 7-16) and prolonged phase (ICU day 17-28) of critical illness.

Secondary outcome measures

Secondary endpoints (clinical parameters and treatment information) will be collected during their stay in ICU

Overall trial start date

20/01/2016

Overall trial end date

31/07/2017

Reason abandoned

Eligibility

Participant inclusion criteria

For patients:
1. Critically ill patients at the surgical or medical intensive care units, with ongoing intensive care dependency, a stable condition for at least 48h, and an expected stay in ICU for at least 48h
2. Age ≥18 years

For healthy volunteers:
1. Age-, gender- and BMI-matched to the included patients

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

Recruitment of patients will continue until the preset number of 40 patients is reached in the 3 patient cohorts, and 20 healthy matched volunteers will be studied

Participant exclusion criteria

For patients:
1. Predisposing factors of adrenal insufficiency
1.1. Cerebral disease with intracranial hypertension threatening the neuroendocrine system
1.2. Pituitary disorders including (pan)hypopituitarism
1.3. Known adrenal disease (Cushing’s syndrome or Addison’s disease)
1.4. Chronic treatment with glucocorticoids, other steroids or anti-steroid chemotherapy within the last 3 months
1.5. IV administration of glucocorticoids within the last 72 hours
1.6. Use of etomidate within the last 72 hours
1.7. Use of azoles within the last 7 days
1.8. Other drugs predisposing to adrenal insufficiency: phenytoin, rifampicin, glitazones, imipramin, phenothiazine, phenobarbital
2. Patients known to be pregnant or nursing
3. No arterial line or central venous catheter in place
4. Ethical restrictions
4.1. Moribund
4.2. Declined participation

For healthy volunteers:
1. Recent history of treatment with HPA-axis interfering drugs

Recruitment start date

01/07/2016

Recruitment end date

30/06/2017

Locations

Countries of recruitment

Belgium

Trial participating centre

University Hospitals Leuven (UZ Leuven)
Herestraat 49
Leuven
3000
Belgium

Sponsor information

Organisation

Katholieke Universiteit Leuven (Belgium)

Sponsor details

Professor Koenraad Debackere
Managing Director
University Administration and Central Services
Krakenstraat 3 - box 5500
Leuven
3000
Belgium
+32 (0)16 32 41 67
koenraad.debackere@kuleuven.be

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Methusalem (long term structural funding by the Flemish Government, Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Fonds Wetenschappelijk Onderzoek

Alternative name(s)

Research Foundation Flanders, Flemish Research Foundation, FWO

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Belgium

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes