NCT05193396 Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment
| NCT ID | NCT05193396 |
| Status | Recruiting |
| Phase | Phase 4 |
| Sponsor | Marianne Andersen |
| Condition | Adrenal Insufficiency |
| Study Type | INTERVENTIONAL |
| Enrollment | 100 participants |
| Start Date | 2022-02-01 |
| Primary Completion | 2026-01 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 4 studies follow an already-approved treatment in real-world conditions to monitor long-term safety and effectiveness.
This trial targets 100 participants in total. It began in 2022-02-01 with a primary completion date of 2026-01.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Cortisol, a glucocorticoid (GC) hormone secreted from the adrenal glands, is essential for survival. Cortisol also possesses anti-inflammatory actions and GC formulations (prednisolone) are used to treat many inflammatory diseases and conditions. Indeed, three percent of the Danish population (≈ 180.000 individuals) redeems at least one prescription of synthetic GC per year and at least 20,000 patients annually discontinue GC treatment. Pharmacological GC therapy suppresses endogenous cortisol production and thereby induce relative adrenal insufficiency (GIA). The risk of GIA as determined by the adrenal corticotrophic hormone (ACTH) stimulation test has previously been reported to ≈ 25 %, but testing after GC treatment is not routinely performed. Indeed, new evidence suggest that the risk of GIA after planned cessation of prednisolone treatment for polymyalgia rheumatic (PMR) or giant cell arteritis (GCA) is substantially lower, probably 2%. The reason for this discrepancy is undoubtedly selection bias in the previous publications and the use of inaccurate cortisol assays. At the same time, however, it was observed that 25% exhibited pronounced symptoms of adrenal insufficiency based on a questionnaire specific for detecting symptoms of adrenal insufficiency, the so-called AddiQoL-30. Concomitantly, the basal cortisol levels in the same group were significantly lower as compared to the group, who exhibited milder or no symptoms attributable to adrenal insufficiency. This observation aligns with the clinical experience that PMR/GCA patients often complain of fatigue after planned cessation of prednisolone treatment. This often occurs in the absence of objective symptoms or signs of residual PMR/GCA disease activity. The scenario has been designated as "the steroid withdrawal syndrome". This may represent a state of relative adrenal insufficiency prompted by long term, high dose prednisolone treatment. The proper way to tackle this clinical conundrum is to perform a proper randomized trial, which so far has not been conducted. Therefore, investigators of this study will perform the first placebo-controlled randomised controlled trial (RCT) in patients with PMR and GCA after planned cessation of GC treatment. Investigators argue that neither watchful waiting nor routine hydrocortisone replacement are infallible. The study will be the first evidence-based guidance and aid to GIA patients and thus meet an important need for many thousand patients.
Eligibility Criteria
Inclusion Criteria: * Age ≥ 50 years * A diagnosis of PMR or GCA in GC free remission for \>2 week and \<12 weeks after treatment with prednisolone (any dosage) for ≥12 weeks Exclusion Criteria: * Known primary or secondary adrenal insufficiency * Known Cushing´s syndrome * Heart failure (New York Heart Association class IV) * Kidney failure with an estimated glomerular filtration rate \<30 mL/min * Liver cirrhosis * Active cancer * Known severe immune deficiency * A history of psychiatric disease requiring treatment by a psychiatric department (for affective disorders only if within the last year before study entry) * Alcohol consumption \>21 units per week * Planned major surgery during the study period at study entry * Use of drugs that interfere with cortisol metabolism/measurements: * Systemic oestrogen treatment within 1 month before study inclusion * Strong CYP3A4 inhibitors or inducers * Use of other glucocorticoid formulations: inhaled, intra-articular or intramuscular injections, creams European steroid group IV applied in genital area * Permitted glucocorticoid formulations: eye-drops, nasal spray, creams European group I-III, and European group IV applied in non-genital area * Inability to provide written informed consent
Contact & Investigator
Marianne S Andersen
PRINCIPAL INVESTIGATOR
Odense University Hospital
Frequently Asked Questions
Who can join the NCT05193396 clinical trial?
This trial is open to participants of all sexes, aged 50 Years or older, studying Adrenal Insufficiency. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05193396 trial and what does that mean for participants?
Phase 4 studies are conducted after a treatment has been approved. They monitor long-term safety and real-world effectiveness in a broader patient population.
Is NCT05193396 currently recruiting?
Yes, NCT05193396 is actively recruiting participants. Contact the research team at marianne.andersen1@rsyd.dk for enrollment information.
Where is the NCT05193396 trial being conducted?
This trial is being conducted at Aarhus, Denmark, Copenhagen, Denmark, Odense, Denmark.
Who is sponsoring the NCT05193396 clinical trial?
NCT05193396 is sponsored by Marianne Andersen. The principal investigator is Marianne S Andersen at Odense University Hospital. The trial plans to enroll 100 participants.