Post-corticosteroid Insufficiency: Search for a Threshold Value for Cortisol at 8 Hours, Prospective Study (SYNASTOPRO)

January 5, 2024 updated by: Assistance Publique - Hôpitaux de Paris
Post-corticosteroid insufficiency is found in 40-60% of patients within 10 weeks following the cessation of prolonged corticosteroid therapy and in 20% of patients still after 1 year. Screening in pediatrics is done by carrying out a dynamic test, often the low-dose Synacthen test, which requires day hospitalization. The investigators established in a single-center retrospective study that plasma cortisol at the start of the test could predict the result of the low-dose Synacthen test in patients treated with chronic corticosteroid therapy using two thresholds. A cortisol < 144 nmol/L makes it possible to predict corticotropic insufficiency with a specificity of 94%, while a plasma cortisol > 317 nmol/L eliminates corticotropic insufficiency with a sensitivity of 95%. These thresholds need to be confirmed by a prospective study, and in a population representative of the diversity of children treated with prolonged corticosteroid therapy. Furthermore, certain studies have demonstrated the benefit of salivary cortisol compared to plasma cortisol. Performing salivary cortisol could facilitate screening in consultation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Synthetic glucocorticoids are widely used in medicine for their anti-inflammatory and immunomodulating effects. There are 1-2% of the population treated with synthetic glucocorticoids; among them, around 0.5% underwent prolonged treatment. Glucocorticoids act to reduce inflammation, to modulate immunity but also, to regulate physiological functions such as glucose or bone homeostasis. This is why, despite great efficiency, glucocorticoids are associated with numerous side effects. One of the most frequent is glucocorticoid-induced adrenal insufficiency (GI-AI), which is caused by exogenous glucocorticoid negative feedback on the pituitary and the hypothalamus that leads to adrenal insufficiency. Within 10 weeks after glucocorticoid treatment withdrawal, more than 40% of the patients displayed biological glucocorticoid insufficiency. It is important to diagnose GI-AI to prevent life-threatening adrenal crisis. Diagnosis of GI-AI is biological. In pediatrics, the Low Dose Short Synacthen Test (LD-SST) is usually used. LD-SST consists of injection of a low dose of Synacthen (1µg) to stimulate the adrenal glands and evaluate their capacity to secrete a cortisol peak superior to 500 nmol/L. Plasma cortisol elevation is measured at T20, T30, and T60 and compared to an unstimulated value at T0. As LD-SST requires an outpatient hospital and multiple blood samples, less than 5% of the patients underwent adrenal testing after prolonged glucocorticoid treatment.

In a retrospective study, the investigators showed that morning plasmatic cortisol value can be used to predict LD-SST outcomes, facilitating GI-AI diagnosis. Based on 91 pediatric patients who underwent LD-SST after prolonged glucocorticoid therapy, the investigators showed that a morning plasma cortisol value superior to 317 nmol/L could rule out the diagnosis of GI-AI with a sensitivity of 95% whereas a value inferior to 144 nmol/L is associated with GI-AI with a specificity of 94%. However, our study had several limits, such as selection bias and population representativity, and those thresholds needed to be confirmed with a larger prospective study.

The main objective of our study is to confirm thresholds of morning plasma cortisol value to diagnose glucocorticoid-induced adrenal insufficiency in a larger population, more representative of the variety of glucocorticoid treatment in pediatrics. Secondary objectives are the evaluation of salivary cortisol values either to replace plasma cortisol value in response to Synacthen or as a single morning cortisol value. The tertiary objective is to determine GI-AI prevalence in children treated with glucocorticoids for more than 3 weeks and to evaluate clinical predictive factors.

It is a prospective bicentric study. The investigator will include patients aged from 6 months to 18 years old who underwent glucocorticoid treatment for at least 3 weeks at a dose superior to or equal to 3 mg/m2/day. As asthma is the most common pediatric pathology to require prolonged glucocorticoid treatment, patients treated with inhaled glucocorticoids for more than 12 months, or more than 6 months if associated with topic glucocorticoids or if the dose is considered high (GINA 2022) will also be included.

Four weeks after treatment discontinuation or tapering, an LD-SST will be performed to diagnose GI-AI. It will be associated with salivary cortisol measurement at T0 and T30. The investigators will evaluate the association between T0 plasma or salivary cortisol values and GI-AI (plasma cortisol < 500 nmol/L after LD-SST). Thresholds of morning plasma or salivary cortisol associated with the presence or absence of GI-AI will be determined using a receiver operating characteristic (ROC) curve. The risk factors of GI-AI will be assessed through linear regression.

The investigators believe that using morning plasma or salivary cortisol values to screen patients after glucocorticoid withdrawal should improve systematic GI-AI screening and, thus, prevention of adrenal crisis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
170

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 6 months - 17 years
  • Treatment with glucocorticoids for at least 3 weeks at doses ≥ 3 mg/m2 prednisone equivalent OR Treatment with inhaled corticosteroids (ICS) for > 12 months OR high-dose ICS > 6 months OR ICS > 6 months at any dose in combination with other topical corticosteroids.
  • Withdrawal of corticosteroid therapy EXCEPT ICS and topical corticosteroids (tapering off) and/or replacement therapy (< 3 mg/m2/day, eq. Prednisone) for at least 4 weeks.
  • Prescription for Synacthen test including 4 blood samples (T0, T20, T30, T60)
  • No objection from a legal representative or the child taken in by the doctor

Exclusion Criteria:

  • Use of glucocorticoids INCLUDING TOPICALS AND ICS in the 12 hours preceding the test
  • Opposition of the child or legal guardians

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Salivary cortisol dosage
saliva sample (1 ml) at 8 & 9 h & at T30
Diagnostic test: Salivary cortisol dosage
saliva sample at 8 - 9h & at T30

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma cortisol
Time Frame: 60 minutes
morning plasmatic cortisol threshold associated with glucocorticoid-induced adrenal insufficiency defined by the Low Dose Short Synacthen Test (LD-SST) response
60 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Salivary cortisol (nmol/L)
Time Frame: 30 minutes
morning salivary cortisol thresholds to predict glucocorticoid-induced adrenal insufficiency measured by LD-SST / Evaluation of salivary cortisol at T30 after Synacthen to replace plasma cortisol assessment
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Caroline STOREY, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 17, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP230745
  • IDRCB: 2023-A01217-38 (Registry Identifier: IDRCB ANSM)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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