Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Phase 1

Completed

• Conditions: Addison Disease; Adrenal Hyperplasia Congenital
• Interventions: Drug: Solu-Cortef; Drug: Cortef

• Registration Number: NCT02096510
• Lead Sponsor: Haukeland University Hospital

Brief Summary

The aim of this study is to compare the effects of tablet treatment, circadian and combined circadian and ultradian subcutaneous hydrocortisone infusion on steroid metabolism and tissue responses to therapy.

Detailed Description

The conventional glucocorticoid replacement therapy in primary adrenal insufficiency (Addison's disease) and congenital adrenal hyperplasia renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. This therapeutical approach does not enable to restore physiological circadian and ultradian rhythm of glucocorticoids. Current studies conclude that constant or unphysiological administration of glucocorticoids leads to abnormal gene transcription and causes sides effect of glucocorticoids treatment and long standing complications Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion, which can mimic not only the normal diurnal cortisol rhythm, but potentially also the ultradian cadence.

This is a pilot trial with an open cross-over design of 3 x minimum 2 weeks in 10 patients comparing the effects of tablet treatment versus continuous subcutaneous hydrocortisone infusion versus ultradian subcutaneous hydrocortisone infusion on serum, salivary, tissue hormonal response and glucocorticoid related gene expression.

Study Timeline

• Study First Submitted: 2013-11-28
• Study First Submitted QC: 2014-03-24
• Study First Posted: 2014-03-26
• Study Start: 2014-03-27
• Primary Completion: 2016-12
• Study Completion: 2017-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. clinical diagnosis of primary adrenal insufficiency
2. Written informed consent

Exclusion Criteria

.

1. Diabetes mellitus
2. Severe cardiovascular disease
3. Active malignant disease
4. Pregnancy or breast feeding
5. treatment with interfering drugs
6. Intake of grapefruit juice

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
cortef tablets	Solu-Cortef	the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.
continuous subcutaneous hydrocortisone	Cortef	continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate
cortef tablets	Cortef	the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.
ultradian subcutaneous hydrocortisone	Cortef	ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate
continuous subcutaneous hydrocortisone	Solu-Cortef	continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate
ultradian subcutaneous hydrocortisone	Solu-Cortef	ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate

Primary Outcome Measures

Name	Time	Method
Serum cortisol -24 hours curve	24 hours	admission to hospital for 24 hours

Secondary Outcome Measures

Name	Time	Method
24 h urine cortisol and metabolites	24 hours	urine samples for 24 hours
Salivary cortisol - 24 hours curve	24 hours	admission to the hospital for 25 hours
24 hours curve of tissue cortisol	24 hours	The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)
levels of corticotropic hormone	24 hours	blood samples
gene expression	24 hours	m RNA expression of genes

Trial Locations

Locations (1)

University Hospital Helse Bergen; 🇳🇴 Bergen, Norway