REPLACE: Hydrocortisone and Placebo in Patients With Partial Adrenal Insufficiency After Cessation of Glucocorticoid Treatment

Marianne Andersen (Other)
Overall Status
Not yet recruiting ID

Study Details

Study Description

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 is ≈ 25 %,but testing after GC treatment is not routinely performed. In addition, the ACTH stimulation testwas developed for the diagnosis of complete primary adrenal insufficiency, wherefore the clinical value of the ACTH stimulation test in the context of GIA is unknown. When diagnosed, GIA is treated with hydrocortisone (equivalent to cortisol). Excess GC exposure is associated with very serious adverse effects which may also apply to hydrocortisone treatment in patients with GIA. Moreover, hydrocortisone treatment may postpone normalization of adrenal function. On the other hand, GIA patients may develop symptomatic adrenal insufficiency that justifies hydrocortisone treatment. Despite these dilemmas, no evidence-based data exist regarding the proper management of GIA patients. The study is a multi-centre, randomised, double-blinded, placebo controlled 1-year study to compare the effect of hydrocortisone and placebo in patients with Giant Cell Arterititis or Polymyalgia Rheumatica (PMR) with partial adrenal insufficiency after cessation of glucocorticoid treatment.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Anticipated Enrollment :
150 participants
Intervention Model:
Parallel Assignment
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Official Title:
A Randomised, Placebo Controlled to Compare the Effect of Hydrocortisone and Placebo in Patients With Partial Adrenal Insufficiency After Cessation of Glucocorticoid Treatment
Anticipated Study Start Date :
Feb 1, 2022
Anticipated Primary Completion Date :
Feb 1, 2024
Anticipated Study Completion Date :
Feb 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Placebo tablets

Drug: Placebo
placebo tablets

Active Comparator: Hydrocortisone

hydrocortisone tablets

Drug: Hydrocortisone

Outcome Measures

Primary Outcome Measures

  1. Adrenal insufficiency symptoms [6 months]

    measured by questionaire: AddiQoL-30

Eligibility Criteria


Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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

Contacts and Locations


No locations specified.

Sponsors and Collaborators

  • Marianne Andersen


  • Principal Investigator: Marianne S Andersen, Odense University Hospital

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
Marianne Andersen, professor, Odense University Hospital Identifier:
Other Study ID Numbers:
First Posted:
Jan 14, 2022
Last Update Posted:
Feb 22, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Product Manufactured in and Exported from the U.S.:
Keywords provided by Marianne Andersen, professor, Odense University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 22, 2022