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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02277587
Recruitment Status : Completed
First Posted : October 29, 2014
Last Update Posted : April 25, 2019
Information provided by (Responsible Party):
Andrea M. Isidori, University of Roma La Sapienza

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
Primary Adrenal Insufficiency Secondary Adrenal Insufficiency Drug: Plenadren Drug: Conventional glucocorticoid therapy 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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 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

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. Bone mineral density [ Time Frame: 0, + 6 months ]
    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02277587

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Department of Experimental Medicine
Rome, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
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Principal Investigator: Andrea M Isidori, MD, PhD Dept. Experimental Medicine
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Andrea M. Isidori, Professor, University of Roma La Sapienza Identifier: NCT02277587    
Other Study ID Numbers: Hyposurrenalism_1
First Posted: October 29, 2014    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Keywords provided by Andrea M. Isidori, University of Roma La Sapienza:
Addison's disease
Cortisone Acetate
Natural Killer cells
Immunological profile
Additional relevant MeSH terms:
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Neoplasm Metastasis
Adrenal Insufficiency
Addison Disease
Neoplastic Processes
Pathologic Processes
Adrenal Gland Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs