NCT02501486

Brief 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. 1.How often do inhalation or nasal corticosteroids lead to suppression of the HPA- axis in HIV-treated patients?
  2. 2.Are other variables associated with the HPA-axis suppression?
  3. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jul 2015

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 2, 2015

Completed
29 days until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
16 days until next milestone

First Posted

Study publicly available on registry

July 17, 2015

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
Last Updated

October 13, 2016

Status Verified

October 1, 2016

Enrollment Period

1.5 years

First QC Date

June 2, 2015

Last Update Submit

October 12, 2016

Conditions

Adrenal Insufficiency

Keywords

adrenal insufficiencyadverse drug reactioncorticosteroid

Outcome Measures

Primary Outcomes (1)

  • 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

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

    baseline

  • Percentage of HPA-axis suppression stratified by type of corticosteroid

    baseline

  • Difference in percentage of HPA-axis suppression in persons who use a high dose of corticosteroids versus a low dose of corticosteroids

    baseline

  • Cortisol measurements in hair to diagnose HPA-axis suppression, in comparison with serum cortisol or an ACTH stimulation test

    baseline

Study Arms (1)

ACTH stimulation test

OTHER

this is a single arm study. An ACTH-stimulation test will be done

Other: ACTH stimulation test

Interventions

ACTH stimulation testOTHER

An ACTH stimulation test will be done

ACTH stimulation test

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Onze lieve vrouw Gasthuis

Amsterdam, Netherlands

RECRUITING

Radboud UMC

Nijmegen, Netherlands

RECRUITING

Related Publications (1)

  • 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.

    PMID: 32140912DERIVED

MeSH Terms

Conditions

Adrenal InsufficiencyDrug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Adrenal Gland DiseasesEndocrine System DiseasesChemically-Induced Disorders

Study Officials

  • David Burger, Prof

    Radboud UMC Pharmacy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

F Besemer

CONTACT

0031243614599

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2015

First Posted

July 17, 2015

Study Start

July 1, 2015

Primary Completion

January 1, 2017

Study Completion

February 1, 2017

Last Updated

October 13, 2016

Record last verified: 2016-10

Locations

NL(2)