Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM) (DREAM)
|ClinicalTrials.gov Identifier: NCT02277587|
Recruitment Status : Completed
First Posted : October 29, 2014
Last Update Posted : April 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Adrenal Insufficiency Secondary Adrenal Insufficiency||Drug: Plenadren Drug: Conventional glucocorticoid therapy||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||89 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Randomized, Controlled, Multi-Centre Trial on the Effects of Dual-release Hydrocortisone Preparations Versus Conventional Glucocorticoid Replacement Therapy in Patients Affected by Primary and Secondary Adrenal Insufficiency. DREAM Trial.|
|Actual Study Start Date :||March 2014|
|Actual Primary Completion Date :||June 2016|
|Actual Study Completion Date :||June 2016|
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.
Oral Tablets: 20-25-30 mg
Other Name: Dual-release Hydrocortisone
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 Name: Hydrocortisone / Cortisone Acetate
No Intervention: Healthy volunteers
Healthy volunteers will be enrolled as control group
- Change from baseline in measurement of weight at 3 and 6 months [ Time Frame: 0, + 3 months, + 6 months ]Single outcome measurement of body weight (kg).
- Change from baseline in metabolic status at 3 and 6 months [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 0, + 6 months ]Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02277587
|Department of Experimental Medicine|
|Rome, Italy, 00161|
|Principal Investigator:||Andrea M Isidori, MD, PhD||Dept. Experimental Medicine|