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

Primary Adrenal Insufficiency Clinical Trial

— DREAM  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02277587
• Other study ID #: Hyposurrenalism_1
• Status: Completed
• Phase: Phase 4
• Start date: March 2014
• Est. completion date: June 2016

Study information

• Verified date: April 2019
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Addison Disease
• Adrenal Insufficiency
• Neoplasm Metastasis
• Primary Adrenal Insufficiency
• Secondary Adrenal Insufficiency

Intervention

Drug:
• Plenadren
Oral Tablets: 20-25-30 mg
• Conventional glucocorticoid therapy
Oral Tablets: 20-25-30- 37.5 mg

Locations

Country	Name	City	State
Italy	Department of Experimental Medicine	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Johannsson G, Bergthorsdottir R, Nilsson AG, Lennernas H, Hedner T, Skrtic S. Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study. Eur J Endocrinol. 2009 Jul;161(1):119-30. doi: 10.153 — View Citation

Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engström BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernäs H, Skrtic S. Improved cortisol exposure-time profile and outcome in patient — View Citation

Nilsson AG, Marelli C, Fitts D, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engström BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Lennernäs H, Skrtic S, Johannsson G. Prospective evaluation of long-term safety of dual-release hydrocortisone re — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in measurement of weight at 3 and 6 months	Single outcome measurement of body weight (kg).	0, + 3 months, + 6 months
Secondary	Change from baseline in metabolic status at 3 and 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.	0, + 3 months, + 6 months
Secondary	Evaluation of immunological profile at baseline 3 and 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.	0, + 3 months, + 6 months
Secondary	Evaluation of bone deposition and resorption markers from baseline at 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.	0, + 6 months
Secondary	Evaluation of epicardial fat thickness from baseline at 6 months	Measurement of epicardial fat thickness (EFT) by hihg-resolution M-B-mode transthoracic echocardiography from baseline at 6 months.	0, + 6 months
Secondary	Evaluation of hepatic steatosis from baseline at 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.	0, + 6 months
Secondary	Changes in quality of life from baseline at 2, 3 and 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).	0, + 2 months, +3 months, + 6 months
Secondary	Bone mineral density	Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)	0, + 6 months