Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment

A Multi-centre, Randomised, Double-blinded, Placebo Controlled 16-weeks Study to Compare the Effect of Hydrocortisone and Placebo in Patients With Giant Cell Arteritis (GCA)/ Polymyalgia Rheumatica (PMR) With Patient-reported Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment.

Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment (NCT05193396) is a Phase 4 interventional studying Adrenal Insufficiency and Polymyalgia Rheumatica (PMR), sponsored by Marianne Andersen. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 100 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Adrenal Insufficiency subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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 willing to sign a consent form Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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

Treatments Being Tested

DRUG

Hydrocortisone

Patients are randomized to oral hydrocortisone (10 mg twice daily) or placebo for 16 weeks.

DRUG

Placebo

Patients are randomized to oral hydrocortisone (10 mg twice daily) or placebo for 16 weeks.

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, Denmark

Department of Nephrology and Endocrinology, Rigshospitalet

Copenhagen, Denmark

Department of Endocrinology, Odense University Hospital

Odense, Denmark

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05193396), the sponsor (Marianne Andersen), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05193396 clinical trial studying?

Who can participate in NCT05193396?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05193396?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05193396. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05193396. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.