Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Conditions
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Addison Disease, Adrenal Hyperplasia Congenital

Intervention / Treatment
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* Drug: Solu-Cortef
* Drug: Cortef


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical diagnosis of primary adrenal insufficiency Written informed consent Exclusion Criteria:. Diabetes mellitus Severe cardiovascular disease Active malignant disease Pregnancy or breast feeding treatment with interfering drugs Intake of grapefruit juice

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: continuous subcutaneous hydrocortisone<br>continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate | Drug: Solu-Cortef<br>* administration by pump for minimum 2 weeks<br>* Other names: hydrocortisone;Drug: Cortef<br>* tablet treatment 2 ro 3 times per day for 14 days<br>* Other names: hydrocortisone tablets;|
| Active Comparator: cortef tablets<br>the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day. | Drug: Solu-Cortef<br>* administration by pump for minimum 2 weeks<br>* Other names: hydrocortisone;Drug: Cortef<br>* tablet treatment 2 ro 3 times per day for 14 days<br>* Other names: hydrocortisone tablets;|
| Experimental: ultradian subcutaneous hydrocortisone<br>ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate | Drug: Solu-Cortef<br>* administration by pump for minimum 2 weeks<br>* Other names: hydrocortisone;Drug: Cortef<br>* tablet treatment 2 ro 3 times per day for 14 days<br>* Other names: hydrocortisone tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cortisol -24 hours curve | admission to hospital for 24 hours | 24 hours | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adrenal Hyperplasia Congenital, Addison Disease