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

NCT02277587 | Completed Phase 4

• 1 other identifier: Hyposurrenalism_1
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Adrenal Insufficiency; Secondary Adrenal Insufficiency

Keywords

Plenadren; Addison's disease; Hydrocortisone; Cortisone Acetate; Monocytes; Natural Killer cells; Immunological profile; Inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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 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

• Evaluation of hepatic steatosis from baseline at 6 months

  0, + 6 months

Study Arms (3)

Plenadren

EXPERIMENTAL

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

Conventional glucocorticoid therapy

ACTIVE COMPARATOR

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

Healthy volunteers

NO INTERVENTION

Healthy volunteers will be enrolled as control group

Interventions

Plenadren DRUG

Oral Tablets: 20-25-30 mg

Also known as: Dual-release Hydrocortisone

Plenadren

Conventional glucocorticoid therapy DRUG

Oral Tablets: 20-25-30- 37.5 mg

Also known as: Hydrocortisone / Cortisone Acetate

Conventional glucocorticoid therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Department of Experimental Medicine

Rome, 00161, Italy

Location

Related Publications (5)

• Nilsson AG, Marelli C, Fitts D, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engstrom BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Lennernas H, Skrtic S, Johannsson G. Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency. Eur J Endocrinol. 2014 Sep;171(3):369-77. doi: 10.1530/EJE-14-0327. Epub 2014 Jun 18.

  PMID: 24944332 RESULT

• Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engstrom BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernas H, Skrtic S. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012 Feb;97(2):473-81. doi: 10.1210/jc.2011-1926. Epub 2011 Nov 23.

  PMID: 22112807 RESULT

• 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: 10.1530/EJE-09-0170. Epub 2009 Apr 21.

  PMID: 19383806 RESULT

• Venneri MA, Hasenmajer V, Fiore D, Sbardella E, Pofi R, Graziadio C, Gianfrilli D, Pivonello C, Negri M, Naro F, Grossman AB, Lenzi A, Pivonello R, Isidori AM. Circadian Rhythm of Glucocorticoid Administration Entrains Clock Genes in Immune Cells: A DREAM Trial Ancillary Study. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2998-3009. doi: 10.1210/jc.2018-00346.

  PMID: 29846607 DERIVED

• Isidori AM, Venneri MA, Graziadio C, Simeoli C, Fiore D, Hasenmajer V, Sbardella E, Gianfrilli D, Pozza C, Pasqualetti P, Morrone S, Santoni A, Naro F, Colao A, Pivonello R, Lenzi A. Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2018 Mar;6(3):173-185. doi: 10.1016/S2213-8587(17)30398-4. Epub 2017 Dec 8.

  PMID: 29229498 DERIVED

MeSH Terms

Conditions

Addison Disease; Inflammation

Interventions

Hydrocortisone; Cortisone

Condition Hierarchy (Ancestors)

Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Andrea M Isidori, MD, PhD

  Dept. Experimental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 24, 2014
• First Posted: October 29, 2014
• Study Start: March 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 25, 2019

Record last verified: 2019-04

Locations

IT (1)