Addison Disease, Adrenal Hyperplasia Congenital
Conditions
Keywords
Addison Disease, Adrenal Hyperplasia Congenital
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.
Interventions
DRUGSolu-Cortef
administration by pump for minimum 2 weeks
DRUGCortef
tablet treatment 2 ro 3 times per day for 14 days
Sponsors
Haukeland University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum cortisol -24 hours curve | 24 hours | admission to hospital for 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Salivary cortisol - 24 hours curve | 24 hours | admission to the hospital for 25 hours |
| 24 h urine cortisol and metabolites | 24 hours | urine samples for 24 hours |
| levels of corticotropic hormone | 24 hours | blood samples |
| 24 hours curve of tissue cortisol | 24 hours | The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis) |
| gene expression | 24 hours | m RNA expression of genes |
Countries
Norway
Outcome results
None listed