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

MI-összefoglaló

A vizsgálat saját részvételi feltételeiből. Gép olvasta ki az oldalon álló regiszterszövegből, ezért tévedhet. Hogy ki vehet részt, azt a lenti regiszterszöveg és a vizsgálat csapata dönti el.

The trial is looking for people aged 50 or older with PMR or GCA who recently stopped prednisolone. It compares hydrocortisone with placebo (dummy tablets) for symptoms of low adrenal function.

Életkor

50 years and older

Nem

All sexes

A betegség stádiuma

Polymyalgia rheumatica (PMR) or giant cell arteritis (GCA) in remission without glucocorticoids for more than 2 weeks and less than 12 weeks.

Korábbi kezelés

Must have had prednisolone (any dose) for 12 weeks or more, and then stopped it.

Biomarker vagy leletérték

Groups are formed by AddiQoL-30 questionnaire score and short Synacthen test cortisol levels. In the treatment groups: AddiQoL-30 score < 85 and/or cortisol > 100 and < 420 nmol/L.

A részvétel fő kizáró okai

• Known adrenal insufficiency or Cushing´s syndrome
• Severe heart failure (NYHA class IV), kidney failure with eGFR <30 mL/min, or liver cirrhosis
• Active cancer or known severe immune deficiency
• Alcohol over 21 units per week, or major surgery planned during the study
• Oestrogen pills or similar within 1 month, strong CYP3A4 inhibitors or inducers, or some other glucocorticoid forms

A regiszter feltételei, szó szerint

Mit akar kideríteni a vizsgálat

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.

A vizsgálat 4 csoportja

• RCT group - PlaceboPlacebo, összehasonlításként

  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.

  Kezelés: Placebo

• RCT group - HydrocortisoneMár használt kezelés, összehasonlításként

  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.

  Kezelés: Hydrocortisone

• Comparator group 1Nincs vizsgálati kezelés, összehasonlításként

  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 2Nincs vizsgálati kezelés, összehasonlításként

  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.