Inhalation/Nasal Corticosteroids and Prevalence of Hypothalamic-pituitary-adrenal (HPA) Axis Suppression in Human Immunodeficiency Virus (HIV)-Patients

Adrenal Insufficiency Clinical Trial

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Official title:

Inhalation or Nasal Corticosteroids and Prevalence of Hypothalamic-pituitary-adrenal Axis Suppression in HIV-infected Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02501486
• Other study ID #: NL51711.091.14
• Status: Recruiting
• Phase: N/A
• First received: June 2, 2015
• Last updated: October 12, 2016
• Start date: July 2015
• Est. completion date: February 2017

Study information

• Verified date: October 2016
• Source: Radboud University
• Contact: F Besemer
• Phone: 0031243614599
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical 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. 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:

1. How often do inhalation or nasal corticosteroids lead to suppression of the HPA- axis in HIV-treated patients?

Secondary objectives:

2. Are other variables associated with the HPA-axis suppression?

3. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: February 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Adrenal Insufficiency
• HIV Infections

Intervention

Other:
• ACTH stimulation test
An ACTH stimulation test will be done

Locations

Country	Name	City	State
Netherlands	Onze lieve vrouw Gasthuis	Amsterdam
Netherlands	Radboud UMC	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	AIDS Fonds, OLVG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	baseline	No
Secondary	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).	baseline	No
Secondary	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).	baseline	No
Secondary	Difference in percentage of HPA-axis suppression in persons who use a high dose of corticosteroids versus a low dose of corticosteroids		baseline	No
Secondary	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.	baseline	No