Effect of Supplemental Hydrocortisone During Stress in Prednisolone-induced Adrenal Insufficiency

NCT05435781 | Recruiting Phase 4

• 4 other identifiers: RESCUE2021-002528-18H-210419302024-518272-30-00
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 3

Brief Summary

In this double-blinded randomised placebo-controlled clinical trial, the aim is to determine the effect of supplemental hydrocortisone compared with placebo during mild to moderate physical or mental stress on health related quality of life in patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) on ongoing low-dose prednisolone diagnosed with glucocorticoid-induced adrenal insufficiency. The main emphasis is on fatigue (primary outcome) and daily variation hereof during periods of stress.

Conditions

Adrenal Insufficiency; Polymyalgia Rheumatica; Giant Cell Arteritis

Keywords

Glucocorticoid-induced adrenal insufficiency; Prednisolone; Glucocorticoids; Hypothalamic-pituitary-adrenal axis

Outcome Measures

Primary Outcomes (1)

• ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA

  EMA in situations of stress. EMA reporting will be conducted electronically on a smartphone.

  In situations of stress, participants are asked to answer the EMA items 5 times daily at semi-randomised time points, for 3 days. Diurnal profiles are generated and one diurnal profile summarizes responses during the day across all 'sick-days'.

Secondary Outcomes (31)

• Daily 'end-of-day' app-facilitated patient reported outcome (PRO) assessments

  Patients are asked daily throughout the study period as 'end-of-day' assessments.

• SF-36

  At baseline, 3 months and 6 months

• AddiQol-30

  At baseline, 3 months and 6 months

• PMR/GCA treatment characteristics -accumulated glucocorticoid dose

  Information from 6 months before baseline to end-of study

• PMR/GCA treatment characteristics -prednisolone treatment duration

  Information from 6 months before baseline to end-of study

Study Arms (3)

RCT group - hydrocortisone

ACTIVE COMPARATOR

Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive hydrocortisone

Drug: Hydrocortisone

RCT group - placebo

PLACEBO COMPARATOR

Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive placebo

Drug: Placebo for hydrocortisone

Control group

NO INTERVENTION

Patients with polymyalgia rheumatica/giant cell arteritis with normal adrenal function (Synacthen test response ≥420 nmol/l)

Interventions

Hydrocortisone DRUG

Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention.

RCT group - hydrocortisone

Placebo for hydrocortisone DRUG

Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention.

RCT group - placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years
• Women must be postmenopausal (FSH is measured at the screening visit)
• A diagnosis of PMR/GCA, or both conditions combined.
• Treatment with prednisolone ≥12 weeks
• Ongoing prednisolone treatment, with current daily prednisolone dose \> 0 mg and ≤5 mg. The dose must have been ≤5 mg for minimum 2 weeks at the time of the screening visit.

You may not qualify if:

• Known primary or secondary adrenal insufficiency
• Known Cushing's Syndrome
• Known allergy towards study medication ingredients
• Severe comorbidity: Heart failure (New York Heart Association class IV); Kidney failure with an estimated glomerular filtration rate \<30 mL/min (Chronic kidney disease stage 4-5); Liver disease in the form of 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.
• Inability to provide written informed consent.

Sponsors & Collaborators

• Aarhus University Hospital: collaborator
• Marianne Christina Klose: lead
• Odense University Hospital: collaborator

Study Sites (3)

Department of Endocrinology, Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Department of Endocrinology, Odense University Hospital

Odense, Denmark

RECRUITING

MeSH Terms

Conditions

Adrenal Insufficiency; Polymyalgia Rheumatica; Giant Cell Arteritis

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Ulla Feldt-Rasmussen, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Marianne Klose, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marianne Klose, MD, PhD

CONTACT

+4530237532; marianne.christina.klose.01@regionh.dk

Stina W. Borresen, MD, PhD

CONTACT

+4525347551; stina.borresen@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients and all study personnel are blinded for study medication (hydrocortisone or placebo)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Model Details: Double-blinded randomised placebo-controlled clinical trial

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 28, 2022
• Study Start: June 7, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (3)