Glucocorticoid Treatment in Addison's Disease

Study Overview
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Brief Summary
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Addison's disease is a rare condition which in most cases is caused by autoimmune destruction of the adrenals, leading to deficiency of cortisol, aldosterone and adrenal androgens. Unrecognized the disease is life threatening, but with proper treatment patients can live near normal lives. The conventional glucocorticoid replacement therapy renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. Glucocorticoid replacement therapy is technically feasible by continuous subcutaneous hydrocortisone infusion (CSHI), and can mimic the normal diurnal cortisol rhythm. This study aims to further evaluate CSHI treatment in terms of metabolic effects, effects on health-related quality-of-life and sleep in an 8 months randomised open label clinical trial with crossover design.

Official Title
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Glucocorticoid Treatment in Addison's Disease

Conditions
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Addison's Disease

Intervention / Treatment
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* Drug: Solu-Cortef (hydrocortisone)
* Drug: Cortef (hydrocortisone)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with verified Addison's disease on stable treatment. Exclusion Criteria: Insulin treated Diabetes Mellitus, cardiovascular disease,malignant disease, pregnancy. Treatment with glucocorticoids or drugs that interfere with cortisol metabolism (antiepileptics, rifampicin, St. John's wart).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral hydrocortisone<br> | Drug: Cortef (hydrocortisone)<br>* Oral treatment 3 times a day. Weight adjusted doses.<br>* Other names: Cortef 5 mg;|
| Experimental: Continous subcutaneous hydrocortisone infusion<br> | Drug: Solu-Cortef (hydrocortisone)<br>* Continuous Subcutaneous Hydrocortisone infusion via insulin pump. Doses adjusted to body surface area.<br>* Other names: Solu-Cortef;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morning (08-09) plasma ACTH |  | Time 0, months 2, 3, 5, 7 and 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-Related Quality of Life; evaluated by SF-36 vitality scores and AddiQoL scores |  | At time 0 and months 2,3,5,7 and 8 | 
| Sleep; evaluated by Pittsburgh Sleep Quality Index (PSQI), and 7-days' Actigraph registration combined with self-reported sleep diary |  | PSQI: 0 and months 2,3,5,7 and 8; Actigraph/sleep diary: months 2 and 7 | 
| 24h cortisol profiles in serum and saliva |  | months 2 and 7 | 
| S-glucose, 24 h profile |  | months 2 and 7 | 
| Insulin sensitivity assessed by euglycemic clamp |  | Months 2 and 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Addison's disease, Glucocorticoid treatment, Continuous subcutaneous hydrocortisone infusion, CSHI, Quality of Life, Sleep