Adrenal InsufficiencyIncorporateNCT02501486
Inhalation/Nasal Corticosteroids and Prevalence of Hypothalamic-pituitary-adrenal (HPA) Axis Suppression in Human Immunodeficiency Virus (HIV)-Patients
A study testing ACTH stimulation test in people with Adrenal Insufficiency, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial summary
Rationale: Case reports describe suppression of the hypothalamic-pituitary-adrenal (HPA) axis caused by local corticosteroids, most often with inhalation corticosteroids. The exact prevalence is not known. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- ACTH stimulation test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jul 2015to Feb 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Receive a treatment for HIV-infection
- > 18 years old
- Current usage of inhalation or nasal corticosteroids, for at least two weeks
- Willing to give informed consent
Who cannot join
- adrenal insufficiency
- Concurrent use of topical corticosteroids, usage of oral corticosteroids in the last three months. Intramuscular or intra-articular corticosteroid injections in the last year.
- Contra-indications for tetracosactide: allergy for tetracosactide, Cushings's syndrome, refractory heart failure, peptic ulcer, acute psychosis, adrenogenital syndrome
- If the patient ever had an ACTH-stimulation test before
- Pregnant female or breast-feeding female.
- Use of oral contraceptives, since these can heighten the cortisol-binding globulin
- Exclusion criterion for the cortisol measurements in hair: baldness
Trial locations and contacts
2 sites in 1 country.
F Besemer contact
Netherlands2 sites, 2 recruiting
- Recruiting
Onze lieve vrouw Gasthuis
Amsterdam
- Recruiting
Radboud UMC
Nijmegen
About this study
Official title: Inhalation or Nasal Corticosteroids and Prevalence of Hypothalamic-pituitary-adrenal Axis Suppression in HIV-infected Patients
Rationale: Case reports describe suppression of the hypothalamic-pituitary-adrenal (HPA) axis caused by local corticosteroids, most often with inhalation corticosteroids. The exact prevalence is not known. Early recognition is important, because suppression of the HPA-axis can lead to significant morbidity and mortality. Suppression of the HPA axis might occur more often when a Cytochrome P450 3A4 (CYP3A4) inhibitor, e.g. ritonavir, is used next to the local corticosteroid, a combination often used by human immunodeficiency virus (HIV)-patients. Cortisol can be determined in hair. This non-invasive analysis could help in diagnosis of suppressed HPA-axis.
Research questions:
Read more
Primary objective:
- How often do inhalation or nasal corticosteroids lead to suppression of the HPA- axis in HIV-treated patients? Secondary objectives:
- Are other variables associated with the HPA-axis suppression?
- Are cortisol measurements in hair as reliable as serum cortisol or an Adrenocorticotropic hormone (ACTH) stimulation test to diagnose suppression of the HPA axis? Study design: cross-sectional explorative study Study population: adults treated for HIV and using an inhalation or nasal corticosteroid.
Intervention: an ACTH stimulation test, cortisol measurements in blood and hair.
Main study parameters/endpoints:
Proportions of persons with a low morning plasma cortisol or low cortisol after an ACTH stimulation test. Correlation between cortisol in plasma and hair cortisol.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Each person will be screened with a history and a short physical examination. A venous cannula will be inserted for obtaining blood for the plasma cortisol and for the ACTH stimulation test. An ACTH stimulation test has no major complications. A piece of hair is cut for cortisol hair analysis. The risks and burden are minimal, while the future benefits could be great since suppression of the endogenous HPA- axis can be associated with morbidities like hypertension or osteoporosis and can even lead to an adrenal crisis when the local corticosteroid is stopped.
- Conditions
- Adrenal Insufficiency
- Being tested
- ACTH stimulation test
- Keywords
- adrenal insufficiency, adverse drug reaction, corticosteroid
- Medical subject headings
- Adrenal Insufficiency, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACTH stimulation testOther
An ACTH stimulation test will be done
| Study group | Role | What they receive |
|---|---|---|
| ACTH stimulation test | Other | this is a single arm study. An ACTH-stimulation test will be done Receives: Other: ACTH stimulation test |
What is being measured
The primary outcome is the main question the study is designed to answer.
the percentage of participants with a morning serum cortisol below 80 nmol/L in morning or below 550 nmol/L after Adrenocorticotropic (ACTH) stimulation test
these are the persons with hypothalamic-pituitary-adrenal (HPA) -axis suppression
Measured: baseline
Secondary outcomes (4)
Difference in percentage of HPA-axis suppression in participants who use a Cytochrome P450 3A4 (CYP3a4) inhibitor (ritonavir or cobicistat) versus percentage of HPA-axis suppression in participants who don't use a booster
HPA-axis suppression is described in outcome 1. If the investigators have enough data the following will also be analysed: duration of usage of inhalation/nasal corticosteroids and use of systemical corticosteroid before (never versus ever used).
Measured: baseline
Percentage of HPA-axis suppression stratified by type of corticosteroid
HPA-axis suppression is described in outcome 1. If the investigators have enough data the following will also be analysed: duration of usage of inhalation/nasal corticosteroids and use of systemical corticosteroid before (never versus ever used).
Measured: baseline
Difference in percentage of HPA-axis suppression in persons who use a high dose of corticosteroids versus a low dose of corticosteroids
Measured: baseline
Cortisol measurements in hair to diagnose HPA-axis suppression, in comparison with serum cortisol or an ACTH stimulation test
hair cortisol measurements are given in pg/mg hair.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2017 (estimated)
- Study completionFeb 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- AIDS Fonds, OLVG
- Responsible party
- Sponsor
- Investigators
- David Burger, Prof, Principal investigator, Radboud UMC Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02501486
- Sponsor's protocol ID
- NL51711.091.14
- Acronym
- Incorporate
- Status last verified
- Oct 2016
- First submitted
- 2 Jun 2015
- Last updated
- 13 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Besemer F, Kramers C, Brinkman K, Hermus ARMM, van Herwaarden AE, Burger DM. Hypothalamic-pituitary-adrenal axis suppression by inhaled or nasal corticosteroids in HIV-infected patients. Int J Clin Pharm. 2020 Apr;42(2):347-350. doi: 10.1007/s11096-020-00995-5. Epub 2020 Mar 5.
PubMed 32140912
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhalation or Nasal Corticosteroids and Prevalence of Hypothalamic-pituitary-adrenal Axis Suppression in HIV-infected Patients
- ClinicalTrials.gov ID
- NCT02501486
- Acronym / sponsor ID
- Incorporate / NL51711.091.14
- Conditions
- Adrenal Insufficiency
- Keywords
- adrenal insufficiency, adverse drug reaction, corticosteroid
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- AIDS Fonds, OLVG
- Study start
- Jul 2015
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Feb 2017 (estimated)
- First posted
- 17 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Case reports describe suppression of the hypothalamic-pituitary-adrenal (HPA) axis caused by local corticosteroids, most often with inhalation corticosteroids. The exact prevalence is not known. Early recognition is important, because suppression of the HPA-axis can lead to significant morbidity and mortality. Suppression of the HPA axis might occur more often when a Cytochrome P450 3A4 (CYP3A4) inhibitor, e.g. ritonavir, is used next to the local corticosteroid, a combination often used by human immunodeficiency virus (HIV)-patients. Cortisol can be determined in hair. This non-invasive analysis could help in diagnosis of suppressed HPA-axis.
Research questions:
Primary objective:
- How often do inhalation or nasal corticosteroids lead to suppression of the HPA- axis in HIV-treated patients? Secondary objectives:
- Are other variables associated with the HPA-axis suppression?
- Are cortisol measurements in hair as reliable as serum cortisol or an Adrenocorticotropic hormone (ACTH) stimulation test to diagnose suppression of the HPA axis? Study design: cross-sectional explorative study Study population: adults treated for HIV and using an inhalation or nasal corticosteroid.
Intervention: an ACTH stimulation test, cortisol measurements in blood and hair.
Main study parameters/endpoints:
Proportions of persons with a low morning plasma cortisol or low cortisol after an ACTH stimulation test. Correlation between cortisol in plasma and hair cortisol.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Each person will be screened with a history and a short physical examination. A venous cannula will be inserted for obtaining blood for the plasma cortisol and for the ACTH stimulation test. An ACTH stimulation test has no major complications. A piece of hair is cut for cortisol hair analysis. The risks and burden are minimal, while the future benefits could be great since suppression of the endogenous HPA- axis can be associated with morbidities like hypertension or osteoporosis and can even lead to an adrenal crisis when the local corticosteroid is stopped.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACTH stimulation test | Other | Other: ACTH stimulation testthis is a single arm study. An ACTH-stimulation test will be done |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Receive a treatment for HIV-infection
- > 18 years old
- Current usage of inhalation or nasal corticosteroids, for at least two weeks
- Willing to give informed consent
Key exclusion criteria (7 listed)
- adrenal insufficiency
- Concurrent use of topical corticosteroids, usage of oral corticosteroids in the last three months. Intramuscular or intra-articular corticosteroid injections in the last year.
- Contra-indications for tetracosactide: allergy for tetracosactide, Cushings's syndrome, refractory heart failure, peptic ulcer, acute psychosis, adrenogenital syndrome
- If the patient ever had an ACTH-stimulation test before
- Pregnant female or breast-feeding female.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACTH stimulation testAn ACTH stimulation test will be done | Other | ACTH stimulation test |
Primary outcome
the percentage of participants with a morning serum cortisol below 80 nmol/L in morning or below 550 nmol/L after Adrenocorticotropic (ACTH) stimulation test
Time frame: baseline
these are the persons with hypothalamic-pituitary-adrenal (HPA) -axis suppression
4 secondary outcomes
Difference in percentage of HPA-axis suppression in participants who use a Cytochrome P450 3A4 (CYP3a4) inhibitor (ritonavir or cobicistat) versus percentage of HPA-axis suppression in participants who don't use a booster
Time frame: baseline
Percentage of HPA-axis suppression stratified by type of corticosteroid
Time frame: baseline
Difference in percentage of HPA-axis suppression in persons who use a high dose of corticosteroids versus a low dose of corticosteroids
Time frame: baseline
Cortisol measurements in hair to diagnose HPA-axis suppression, in comparison with serum cortisol or an ACTH stimulation test
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2016.
- Derived from this study: PubMed 32140912Besemer F, Kramers C, Brinkman K, Hermus ARMM, van Herwaarden AE, Burger DM. Hypothalamic-pituitary-adrenal axis suppression by inhaled or nasal corticosteroids in HIV-infected patients. Int J Clin Pharm. 2020 Apr;42(2):347-350. doi: 10.1007/s11096-020-00995-5. Epub 2020 Mar 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
F Besemer contact
David Burger, Prof principal investigator
Radboud UMC Pharmacy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ACTH stimulation test in people with Adrenal Insufficiency, run by Radboud University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact F Besemer (0031243614599), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the percentage of participants with a morning serum cortisol below 80 nmol/L in morning or below 550 nmol/L after Adrenocorticotropic (ACTH) stimulation test (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02501486, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2016.