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Taking peoplePhase 4

Hydrocortisone versus placebo for adrenal insufficiency symptoms after stopping steroids for GCA or PMR

Tests hydrocortisone against placebo in people with giant cell arteritis or polymyalgia rheumatica.

Key facts

Who runs it
Marianne Andersen
Where
Denmark3 sites in 1 countryChoose a country to see its sites
Registry title
Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment
Status
Recruiting
Phase
Phase 4
People taking part
100 people, planned
Started
1 Feb 2022
Planned end
Jan 2026
Type of study
Interventional, 4 groupsOne group gets an existing treatment, for comparison.
Treatments tested
  • Hydrocortisone
  • Placebo
Record updated
22 December 2025

Who can take part

Age
50 years and older
Sex
Women and men
Healthy volunteers
Cannot take part

The registry criteria, word for word

Show all 18 criteriaShow less

Who can take part

  • 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 cannot take part

  • 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
  • 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
  • Active cancer
  • A history of psychiatric disease requiring treatment by a psychiatric department (for affective disorders only if within the last year before study entry)
  • Liver cirrhosis
  • Known severe immune deficiency
  • Alcohol consumption >21 units per week
  • 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

This trial has no sites in United States.

It has sites in one country. Choose a country to see its sites.

About the trial

What the trial wants to find out

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.

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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.

The 4 groups in the trial

  • RCT group - PlaceboPlacebo, for comparison

    Included patients with an AddiQoL-30 score \< 85 and/or short Synacthen test stimulated plasma cortisol levels \> 100 and \< 420 nmol/L that are radomized to recieve placebo tablets.

    Treatment: Placebo

  • RCT group - HydrocortisoneExisting treatment, for comparison

    Included patients with an AddiQoL-30 score \< 85 and/or short Synacthen test stimulated plasma cortisol levels \> 100 and \< 420 nmol/L that are radomized to recieve hydrocortisone tablets.

    Treatment: Hydrocortisone

  • Comparator group 1No study treatment, for comparison

    Patients with an AddiQoL-30 score \> 85 and short Synacthen test stimulated plasma cortisol level \> 420 nmol/L. Patients undergo baseline examination only.

  • Comparator group 2No study treatment, for comparison

    Patients with pronounced adrenal insufficiency (short Synacthen test stimulated plasma cortisol levels \< 100 nmol/L) - regardless of AddiQoL-30 score. These patients undergo baseline examination and commence open hydrocortisone replacement according to standard clinical practice.

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

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Data and sources

Registry record
Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
Official title
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.
Plain-language title
Hydrocortisone versus placebo for adrenal insufficiency symptoms after stopping steroids for GCA or PMRGenerated from the registry record. The registry title is the official one.
Publications
Record updated
22 December 2025