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.
Overview
- Phase
- Phase 4
- Intervention
- Plenadren
- Conditions
- Primary Adrenal Insufficiency
- Sponsor
- University of Roma La Sapienza
- Enrollment
- 89
- Locations
- 1
- Primary Endpoint
- Change from baseline in measurement of weight at 3 and 6 months
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Andrea M. Isidori
Professor
University of Roma La Sapienza
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: Plenadren
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.
Intervention: Conventional glucocorticoid therapy
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- Change from baseline in metabolic status at 3 and 6 months(0, + 3 months, + 6 months)
- Evaluation of immunological profile at baseline 3 and 6 months.(0, + 3 months, + 6 months)
- Evaluation of hepatic steatosis from baseline at 6 months(0, + 6 months)
- Evaluation of bone deposition and resorption markers from baseline at 6 months(0, + 6 months)
- Evaluation of epicardial fat thickness from baseline at 6 months(0, + 6 months)
- Changes in quality of life from baseline at 2, 3 and 6 months(0, + 2 months, +3 months, + 6 months)
- Bone mineral density(0, + 6 months)