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

Sponsor

Marianne Andersen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05193396

Collaborator

(none)

150

Enrollment

Arms

Anticipated Duration (Months)

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
Adrenal Insufficiency	Drug: Hydrocortisone Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 hydrocortisone

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo tablets

Drug: Placebo

placebo tablets

Active Comparator: Hydrocortisone

hydrocortisone tablets

Drug: Hydrocortisone

hydrocortisone

Outcome Measures

Primary Outcome Measures

Adrenal insufficiency symptoms [6 months]
measured by questionaire: AddiQoL-30

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

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

Locations

No locations specified.

Sponsors and Collaborators

Marianne Andersen

Investigators

Principal Investigator: Marianne S Andersen, Odense University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Marianne Andersen, professor, Odense University Hospital

ClinicalTrials.gov Identifier:

NCT05193396

Other Study ID Numbers:

REPLACE

First Posted:

Jan 14, 2022

Last Update Posted:

Feb 22, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

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

tertiary adrenal insufficiency

Additional relevant MeSH terms:

Adrenal Insufficiency

Hydrocortisone

Study Results

No Results Posted as of Feb 22, 2022