Addison DiseasePhase 1/2NCT02096510

Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

A Phase 1/2 study testing Solu-Cortef and Cortef in people with Addison Disease and Adrenal Hyperplasia Congenital, run by Haukeland University Hospital at 1 site in Norway.

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

The aim of this study is to compare the effects of tablet treatment, circadian and combined circadian and ultradian subcutaneous hydrocortisone infusion on steroid metabolism and tissue responses to therapy. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Addison Disease, Adrenal Hyperplasia Congenital
What is being tested?: Solu-Cortef and Cortef
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteNorway
Study dates: 27 Mar 2014to Dec 2017
Phase: Phase 1/2
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

clinical diagnosis of primary adrenal insufficiency
Written informed consent

Who cannot join

Diabetes mellitus
Severe cardiovascular disease
Active malignant disease
Pregnancy or breast feeding
treatment with interfering drugs
Intake of grapefruit juice

Trial locations and contacts

1 site in 1 country.

Norway1 site

University Hospital Helse Bergen
Bergen, 5021

Other trials in Norway

About this study

Read the detailed description

The conventional glucocorticoid replacement therapy in primary adrenal insufficiency (Addison's disease) and congenital adrenal hyperplasia renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. This therapeutical approach does not enable to restore physiological circadian and ultradian rhythm of glucocorticoids. Current studies conclude that constant or unphysiological administration of glucocorticoids leads to abnormal gene transcription and causes sides effect of glucocorticoids treatment and long standing complications Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion, which can mimic not only the normal diurnal cortisol rhythm, but potentially also the ultradian cadence.

This is a pilot trial with an open cross-over design of 3 x minimum 2 weeks in 10 patients comparing the effects of tablet treatment versus continuous subcutaneous hydrocortisone infusion versus ultradian subcutaneous hydrocortisone infusion on serum, salivary, tissue hormonal response and glucocorticoid related gene expression.

Conditions: Addison Disease, Adrenal Hyperplasia Congenital
Being tested: Solu-Cortef, Cortef
Keywords: Addison Disease, Adrenal Hyperplasia Congenital
Medical subject headings: Addison Disease, Adrenal Hyperplasia, Congenital

What participants receive

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

Solu-CortefDrug
Also called hydrocortisone
administration by pump for minimum 2 weeks
CortefDrug
Also called hydrocortisone tablets
tablet treatment 2 ro 3 times per day for 14 days

Study groups in NCT02096510
Study group	Role	What they receive
continuous subcutaneous hydrocortisone	Experimental	continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate Receives: Drug: Solu-Cortef; Drug: Cortef
cortef tablets	Active comparator	the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day. Receives: Drug: Solu-Cortef; Drug: Cortef
ultradian subcutaneous hydrocortisone	Experimental	ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate Receives: Drug: Solu-Cortef; Drug: Cortef

What is being measured

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

Serum cortisol -24 hours curve
admission to hospital for 24 hours
Measured: 24 hours

Secondary outcomes (5)

Salivary cortisol - 24 hours curve
admission to the hospital for 25 hours
Measured: 24 hours
24 h urine cortisol and metabolites
urine samples for 24 hours
Measured: 24 hours
levels of corticotropic hormone
blood samples
Measured: 24 hours
24 hours curve of tissue cortisol
The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)
Measured: 24 hours
gene expression
m RNA expression of genes
Measured: 24 hours

Timeline

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

27 Mar 2014Dec 2017

First posted26 Mar 2014 (estimated)
Study start27 Mar 2014
Primary completionDec 2016
Study completionDec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Addison DiseaseStudies of the same condition, open and under way.
More trials run by Haukeland University HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02096510
Sponsor's protocol ID: 2013/1738
Status last verified: Jun 2024
First submitted: 28 Nov 2013
Last updated: 7 Jun 2024
Results posted: No
Data monitoring committee: Yes

Publications

Lightman SL, Conway-Campbell BL. The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration. Nat Rev Neurosci. 2010 Oct;11(10):710-8. doi: 10.1038/nrn2914. Epub 2010 Sep 15.
PubMed 20842176
Lovas K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. 2007 Jul;157(1):109-12. doi: 10.1530/EJE-07-0052.
PubMed 17609409
Lightman SL, Windle RJ, Julian MD, Harbuz MS, Shanks N, Wood SA, Kershaw YM, Ingram CD. Significance of pulsatility in the HPA axis. Novartis Found Symp. 2000;227:244-57; discussion 257-60. doi: 10.1002/0470870796.ch14.
PubMed 10752074
Simunkova K, Lovas K, Methlie P, Jovanovic N, Bifulco E, Bronstad I, Lightman SL, Husebye ES, Oksnes M. Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency. Horm Metab Res. 2023 Jul;55(7):471-478. doi: 10.1055/a-2092-5228. Epub 2023 May 12.
PubMed 37172949

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
Primordial Dwarfism Registry
MOPDII, Meier-Gorlin Syndrome
Recruiting
Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders
Cushing Syndrome, Adrenal Insufficiency
RecruitingObservational study
Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

All Addison Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
ClinicalTrials.gov ID: NCT02096510
Acronym / sponsor ID: 2013/1738
Conditions: Addison Disease, Adrenal Hyperplasia Congenital
Keywords: Addison Disease, Adrenal Hyperplasia Congenital
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Haukeland University HospitalUniversity, hospital or other
Study start: 27 Mar 2014 (actual)
Primary completion: Dec 2016 (actual)
Study completion: Dec 2017 (actual)
First posted: 26 Mar 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
continuous subcutaneous hydrocortisone	Experimental	Drug: Solu-Cortef, Drug: Cortefcontinuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate
cortef tablets	Active comparator	Drug: Solu-Cortef, Drug: Cortefthe patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.
ultradian subcutaneous hydrocortisone	Experimental	Drug: Solu-Cortef, Drug: Cortefultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

clinical diagnosis of primary adrenal insufficiency
Written informed consent

Key exclusion criteria (6 listed)

Diabetes mellitus
Severe cardiovascular disease
Active malignant disease
Pregnancy or breast feeding
treatment with interfering drugs

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Solu-CortefAlso: hydrocortisoneadministration by pump for minimum 2 weeks	Drug	continuous subcutaneous hydrocortisone, cortef tablets, ultradian subcutaneous hydrocortisone
CortefAlso: hydrocortisone tabletstablet treatment 2 ro 3 times per day for 14 days	Drug	continuous subcutaneous hydrocortisone, cortef tablets, ultradian subcutaneous hydrocortisone

Primary outcome

Serum cortisol -24 hours curve
Time frame: 24 hours
admission to hospital for 24 hours

5 secondary outcomes

Salivary cortisol - 24 hours curve
Time frame: 24 hours
24 h urine cortisol and metabolites
Time frame: 24 hours
levels of corticotropic hormone
Time frame: 24 hours
24 hours curve of tissue cortisol
Time frame: 24 hours
gene expression
Time frame: 24 hours

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
Background: PubMed 20842176Lightman SL, Conway-Campbell BL. The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration. Nat Rev Neurosci. 2010 Oct;11(10):710-8. doi: 10.1038/nrn2914. Epub 2010 Sep 15.
Background: PubMed 17609409Lovas K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. 2007 Jul;157(1):109-12. doi: 10.1530/EJE-07-0052.
Background: PubMed 10752074Lightman SL, Windle RJ, Julian MD, Harbuz MS, Shanks N, Wood SA, Kershaw YM, Ingram CD. Significance of pulsatility in the HPA axis. Novartis Found Symp. 2000;227:244-57; discussion 257-60. doi: 10.1002/0470870796.ch14.
Results publication: PubMed 37172949Simunkova K, Lovas K, Methlie P, Jovanovic N, Bifulco E, Bronstad I, Lightman SL, Husebye ES, Oksnes M. Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency. Horm Metab Res. 2023 Jul;55(7):471-478. doi: 10.1055/a-2092-5228. Epub 2023 May 12.

Related trials for Addison Disease

RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
Primordial Dwarfism Registry
MOPDII, Meier-Gorlin Syndrome
Recruiting
Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders
Cushing Syndrome, Adrenal Insufficiency
RecruitingObservational study
Natural History of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Katerina Simunkova, MD, PhD principal investigator

Universtity of Bergen

Kristian Løvås, MD, PhD study director

Helse Bergen

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Solu-Cortef and Cortef in people with Addison Disease and Adrenal Hyperplasia Congenital, run by Haukeland University Hospital at 1 site in Norway.

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 6 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 7 Jun 2024. 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 Norway. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Serum cortisol -24 hours curve (time frame: 24 hours). 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 NCT02096510, which also lists 4 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 7 Jun 2024.