Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM)

University of Roma La Sapienza

Status and phase: Completed; Phase 4

Conditions: Primary Adrenal Insufficiency; Secondary Adrenal Insufficiency

Treatments: Drug: Conventional glucocorticoid therapy; Drug: Plenadren

Study type: Interventional

Funder types: Other

Identifiers

NCT02277587

Hyposurrenalism_1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 89 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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89 participants in 3 patient groups

Plenadren

Experimental group

Description:

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.

Treatment:

Drug: Plenadren

Conventional glucocorticoid therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Conventional glucocorticoid therapy

Healthy volunteers

No Intervention group

Description:

Healthy volunteers will be enrolled as control group