Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Haukeland University Hospital

Status and phase: Completed; Phase 2; Phase 1

Conditions: Adrenal Hyperplasia Congenital; Addison Disease

Treatments: Drug: Cortef; Drug: Solu-Cortef

Study type: Interventional

Funder types: Other

Identifiers

NCT02096510

2013/1738

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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8 participants in 3 patient groups

continuous subcutaneous hydrocortisone

Experimental group

Description:

continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate

Treatment:

Drug: Cortef

Drug: Solu-Cortef

cortef tablets

Active Comparator group

Description:

the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.

Treatment:

Drug: Cortef

Drug: Solu-Cortef

ultradian subcutaneous hydrocortisone

Experimental group

Description:

ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate

Treatment:

Drug: Cortef

Drug: Solu-Cortef