Primary Adrenal Insufficiency, Secondary Adrenal Insufficiency
Conditions
Keywords
Plenadren, Addison's disease, Hydrocortisone, Cortisone Acetate, Monocytes, Natural Killer cells, Immunological profile, Inflammation
Brief summary
This is a randomized, controlled, open, three-armed, multi-centre study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on anthropometric parameters, metabolic syndrome, infectious, immunological profile, cardiovascular system, bone mass and quality of life in patients affected by primary or secondary adrenal insufficiency.
Detailed description
Hypocortisolism is a disease with more than 80% 1-year mortality before the availability of synthetic glucocorticoids. Current replacement therapy has improved this dramatically, but recent data suggest that outcome is still compromised. Patient receiving conventional glucocorticoids therapy have compromised quality of life, reduced bone mass, increased risk factors for cardiovascular disease, infectious, tumors and premature mortality that is more than twice the mortality rate in the background population. Circulating cortisol levels follow a distinct diurnal pattern with high levels in the early morning and low trough values around midnight. Using available formulations for replacement therapy this circadian rhythm is had to mimic and also during the active time of the day high peaks and low troughs occur. In this trial a dual-release hydrocortisone preparations that has in healthy volunteers been able to mimic the circadian pattern of circulating cortisol was studied in patients with primary and secondary adrenal insufficiency.
Interventions
DRUGPlenadren
Oral Tablets: 20-25-30 mg
DRUGConventional glucocorticoid therapy
Oral Tablets: 20-25-30- 37.5 mg
Sponsors
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Previously diagnosed (e.g. more than 6 months ago) primary or secondary adrenal insufficiency with a stable daily glucocorticoid substitution dose for at least 3 months prior to study entry * Signed informed consent to participate in the study
Exclusion criteria
* acute primary or secondary adrenal insufficiency * clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepatobiliary, pancreatic disease * clinically significant renal dysfunction * any medication with agents which could interfere with glucocorticoid kinetics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in measurement of weight at 3 and 6 months | 0, + 3 months, + 6 months | Single outcome measurement of body weight (kg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of immunological profile at baseline 3 and 6 months. | 0, + 3 months, + 6 months | Composite outcome measure consisting of simultaneous measurment of: Full Count Blood Cell, ESR, Fibrinogen, Immunoglobulin, PCR; measured at baseline, 3 and 6 months. |
| Evaluation of bone deposition and resorption markers from baseline at 6 months | 0, + 6 months | Composite outcome measure consisting of simultaneous measurment of: serum calcium, phosphate, parathyroid hormone (PTH), 25OH-vitamin D, phosphate, osteocalcin, bone phosphate alkaline (sBALP), serum-cross-linked N and C-telopeptide of bone type I collagen (NTx- CTx); measure at baseline and 6 months. |
| Evaluation of epicardial fat thickness from baseline at 6 months | 0, + 6 months | Measurement of epicardial fat thickness (EFT) by hihg-resolution M-B-mode transthoracic echocardiography from baseline at 6 months. |
| Change from baseline in metabolic status at 3 and 6 months | 0, + 3 months, + 6 months | Composite outcome measure consisting of simultaneous measurment of: Glycaemia, Insulinemia, Homa index, Glycated Haemoglobin, Total Cholesterol, LDL cholesterol, HDL cholesterol, Triglyceredes; the composite outcome measured at 3 and 6 months. |
| Changes in quality of life from baseline at 2, 3 and 6 months | 0, + 2 months, +3 months, + 6 months | Quality of life will be measured by questionnaires: AddiQol, Middle Sex Hospital Questionnaire (MHQ), International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), Beck Depression Inventory Test (BDI-II). |
| Bone mineral density | 0, + 6 months | Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA) |
| Evaluation of hepatic steatosis from baseline at 6 months | 0, + 6 months | Evaluation of hepatic steatosis by conventional ultrasound of the liver and with ASQ software with dedicated equipment and 7-5 Mhz convex probe frome baseline at 6 months. |
Countries
Italy
Outcome results
None listed