Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Plenadren Plenadren (modified release hydrocortison) 20-25 or 30 mg oral tablets will be administered once-daily at 8.00 AM in the fasting state The dose is kept the same as patients had before entering the trial. |
Drug: Plenadren
Oral Tablets: 20-25-30 mg
Other Names:
|
Active Comparator: Conventional glucocorticoid therapy Hydrocortisone (dose range 10 to 30) mg will be continued as before entering the study. Cortisone Acetate (dose 25 to 37.5 mg) will be continued as before entering the study. The morning dose will be administered in the fasting state. The total daily dose and timing is not changed during the study period. |
Drug: Conventional glucocorticoid therapy
Oral Tablets: 20-25-30- 37.5 mg
Other Names:
|
No Intervention: Healthy volunteers Healthy volunteers will be enrolled as control group |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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)
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Signed informed consent to participate in the study
Exclusion Criteria:
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acute primary or secondary adrenal insufficiency
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clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepatobiliary, pancreatic disease
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clinically significant renal dysfunction
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any medication with agents which could interfere with glucocorticoid kinetics
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Department of Experimental Medicine | Rome | Italy | 00161 |
Sponsors and Collaborators
- University of Roma La Sapienza
Investigators
- Principal Investigator: Andrea M Isidori, MD, PhD, Dept. Experimental Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Hyposurrenalism_1