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Primary Adrenal InsufficiencyPhase 4DREAMNCT02277587

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

A Phase 4 study testing Plenadren and Conventional glucocorticoid therapy in people with Primary Adrenal Insufficiency and Secondary Adrenal Insufficiency, run by University of Roma La Sapienza at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
What is being tested?
Plenadren and Conventional glucocorticoid therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
1 siteItaly
Study dates
Mar 2014to Jun 2016
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Italy1 site

  • Department of Experimental Medicine

    Rome, 00161

Other trials in Italy

About this study

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.

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.

Read the 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.

Being tested
Plenadren, Conventional glucocorticoid therapy
Keywords
Plenadren, Addison's disease, Hydrocortisone, Cortisone Acetate, Monocytes, Natural Killer cells, Immunological profile, Inflammation
Medical subject headings
Addison Disease, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlenadrenDrug

    Also called Dual-release Hydrocortisone

    Oral Tablets: 20-25-30 mg

  • Conventional glucocorticoid therapyDrug

    Also called Hydrocortisone / Cortisone Acetate

    Oral Tablets: 20-25-30- 37.5 mg

Study groups in NCT02277587
Study groupRoleWhat they receive
PlenadrenExperimentalPlenadren (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.
Receives: Drug: Plenadren
Conventional glucocorticoid therapyActive comparatorHydrocortisone (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.
Receives: Drug: Conventional glucocorticoid therapy
Healthy volunteersNo interventionHealthy volunteers will be enrolled as control group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from baseline in measurement of weight at 3 and 6 months

    Single outcome measurement of body weight (kg).

    Measured: 0, + 3 months, + 6 months

Secondary outcomes (7)

  1. 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.

    Measured: 0, + 3 months, + 6 months

  2. 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.

    Measured: 0, + 3 months, + 6 months

  3. 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.

    Measured: 0, + 6 months

  4. 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.

    Measured: 0, + 6 months

  5. 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.

    Measured: 0, + 6 months

  6. 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).

    Measured: 0, + 2 months, +3 months, + 6 months

  7. Bone mineral density

    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)

    Measured: 0, + 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionJun 2016
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02277587
Sponsor's protocol ID
Hyposurrenalism_1
Acronym
DREAM
Status last verified
Apr 2019
First submitted
24 Oct 2014
Last updated
25 Apr 2019
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24944332

  • 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.

    PubMed 22112807

  • 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.

    PubMed 19383806

  • 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.

    PubMed 29846607

  • 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.

    PubMed 29229498

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Plenadren and Conventional glucocorticoid therapy in people with Primary Adrenal Insufficiency and Secondary Adrenal Insufficiency, run by University of Roma La Sapienza at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in measurement of weight at 3 and 6 months (time frame: 0, + 3 months, + 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02277587, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2019.

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