AzTrials
AzTrials

Primary Adrenal InsufficiencyNCT03793114

Screening and Stimulation Testing for Residual Secretion of Adrenal Steroid Hormones in Autoimmune Addison's Disease

A study testing Cosyntropin stimulation test, Baseline blood tests and 30-hour ambulatory sampling of intestinal fluid in people with Primary Adrenal Insufficiency, run by University of Bergen at 3 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

In autoimmune adrenal insufficiency, or Addison's disease (AD), the immune system attacks the adrenal cortex. As a result, the adrenal cells producing hormones such as cortisol and aldosterone are destroyed, leaving the body with insufficient levels to meet its needs. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Primary Adrenal Insufficiency
What is being tested?
Cosyntropin stimulation test, Baseline blood tests and 30-hour ambulatory sampling of intestinal fluid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
3 sitesin 3 countries
Study dates
26 Sep 2018to 31 Dec 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women with AAD, age 18-70 years old. This requires documented adrenal insufficiency and a positive test for 21-hydroxylase autoantibodies (biomarker for autoimmune cause) on at least one occasion.
  • Provided written informed consent
  • In case of concomitant endocrine/autoimmune diseases, the patients should be on stable adequate treatment at least the last 3 months prior to the study period.
  • For Norwegian AD patients: enrolled in ROAS
  • For Swedish AD patients: enrolled in the Swedish Addison registry

Who cannot join

  • Antihypertensive treatment, with the exception of doxazosin, verapamil, and moxonidine.
  • Active malignant disease, severe heart, kidney or liver failure.
  • Diabetes mellitus type 1.
  • Pregnancy or breast feeding.
  • Pharmacological treatment with glucocorticoids (except their usual cortisone or hydrocortisone replacement therapy) or drugs that interfere with cortisol and catecholamine metabolism (antiepileptics, rifampicin, St. Johns wart).
  • Use of other glucocorticoid replacement medication than cortisone acetate or hydrocortisone.
  • Intake of grapefruit, grapefruit juice, or and liquorice juice the last week before or during the study period.

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Germany1 site
  • Endokrinologie in Charlottenburg

    Berlin, State of Berlin, 10627

Other trials in Germany

Norway1 site
  • Haukeland University Hospital

    Bergen, Bergen, 5021

Other trials in Norway

Sweden1 site
  • Karolinska Institutet

    Stockholm, Stockholm County, 171 77

Other trials in Sweden

About this study

Official title: Residual Secretion of Adrenal Steroid Hormones in Addison's Disease

In autoimmune adrenal insufficiency, or Addison's disease (AD), the immune system attacks the adrenal cortex. As a result, the adrenal cells producing hormones such as cortisol and aldosterone are destroyed, leaving the body with insufficient levels to meet its needs. The common perception is that upon diagnosis of Addison's disease, basically all adrenal hormone production has ceased.

There have, however, been found a few individuals who preserve some residual secretion of cortisol even years after diagnosis. The objectives of this study is to find out how common it is, and to explore if residual function have impact on patient outcome. That is, do patients with and without residual function differ when it comes to quality of life, working ability, medication dosages, and risk of adrenal crisis?

Read the detailed description

Autoimmune destruction of the adrenal cortex is the main cause of primary adrenal insufficiency (Addison's disease, AD). Autoimmune AD (AAD) becomes clinically manifest when 90 % of cortex of adrenal gland is destroyed. Current dogma says that adrenal insufficiency ultimately is complete, that is the adrenal cortex stops producing steroids altogether. However, several case reports indicate that there might be a subgroup of patients that retain some steroid production, even years after the diagnosis. This ability could be beneficial as it could protect against adrenal crises, ease medication, and leave the patient with better quality of life.

The objective of the study is to systematically assess to what extent patients with AAD have residual adrenocortical function, and to characterize this subgroup.

The study will be an open non-randomized three-stage multicenter clinical trial comprising patients from the Norwegian Registry for organ-specific autoimmune disease (ROAS), the Swedish Addison registry, and Germany. In stage 1, patients will be asked to fill out questionnaires and deliver medication-fasting samples for analyses of adrenal steroids. In addition, patients with congenital adrenal hyperplasia (CAH) and bilaterally adrenalectomized will serve as negative controls for adrenal steroids. In stage 2, AAD patients with residual steroid production will be invited to a cosyntropin stimulation test to estimate the maximum steroid output from the adrenal glands. Twenty patients with no sign of residual function will also be tested as a control group. In stage 3, AAD patients with confirmed residual function will be invited to go through a 30-hour ambulatory sampling of interstitial fluid for investigation of diurnal variation in adrenocortical hormone levels. Also, newly diagnosed AAD patients will be invited to repeated cosyntropin testing as a means of delineating the natural progression of adrenocortical failure.

Being tested
Cosyntropin stimulation test, Baseline blood tests, 30-hour ambulatory sampling of intestinal fluid, Blood test
Medical subject headings
Addison Disease

What participants receive

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

  • Cosyntropin stimulation testDiagnostic test

    Also called Synacthen stimulation test

    Blood samples are taken before (0 min), and 30 and 60 min after intravenously administration of 250 µg cosyntropin (tetracosactide acetate) with the patient placed in the recumbent position. The test will be performed non-fasting (but medication-fasting) between 08:00 and 10:00 a.m.

  • Baseline blood testsDiagnostic test

    Medication-fasting morning levels of adrenocortical hormones.

  • 30-hour ambulatory sampling of intestinal fluidDevice

    30-hour ambulatory sampling of intestinal fluid for analysis of adrenocortical hormones.

  • Blood testOther

    Cardiovascular and inflammatory biomarker profiles

Study groups in NCT03793114
Study groupRoleWhat they receive
Detectable levels of adrenal hormonesExperimentalPatients with detectable serum levels of adrenal hormones will go through cosyntropin stimulation testing.
Receives: Diagnostic Test: Cosyntropin stimulation test
Controls with undetectable hormone levelsActive comparatorTwenty patients without detectable serum levels of adrenal hormones will serve as controls in cosyntropin stimulation testing.
Receives: Diagnostic Test: Cosyntropin stimulation test
Undetectable levels of adrenal hormonesNo interventionPatients without detectable serum levels of adrenal hormones. Cosyntropin stimulation testing will not be performed.
Congenital adrenal hyperplasia (CAH) control groupOtherMapping adrenal steroid profile in patients with congenital adrenal hyperplasia (CAH) with confirmed total deficiency of 21-hydroxylase.
Receives: Diagnostic Test: Baseline blood tests
Bilaterally adrenalectomized control groupOtherMapping adrenal steroid profile in patients who are bilaterally adrenalectomized.
Receives: Diagnostic Test: Baseline blood tests
Diurnal variation in residual adrenocortical hormone levelsExperimentalPatients with detectable serum levels of adrenal hormones will go through a 30-hour ambulatory sampling of interstitial fluid for mapping of any diurnal variation in endogenous adrenocortical secretion.
Receives: Device: 30-hour ambulatory sampling of intestinal fluid
Repeated cosyntropin testing in newly diagnosed patientsExperimentalNewly diagnosed patients will be invited to go through repeated cosyntropin testing to delineate the natural progression of adrenocortical failure.
Receives: Diagnostic Test: Cosyntropin stimulation test
Cardiovascular and inflammatory biomarkersActive comparatorCompare cardiovascular and inflammatory biomarker profiles in patients with and without residual production of adrenocortical steroids
Receives: Other: Blood test

What is being measured

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

  1. The percentage of included patients with residual secretion of cortisol and aldosterone.

    Percentage of included patients with detectable levels of adrenal steroid hormones.

    Measured: 1 day

Secondary outcomes (34)
  1. Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines

    Levels in blood samples

    Measured: 1 day

  2. Medication-fasting basal levels of cortisol

    Levels in blood samples

    Measured: 1 day

  3. Medication-fasting basal levels of cortisol

    Levels in urine samples

    Measured: 1 day

  4. Medication-fasting basal levels of cortisol

    Levels in hair samples

    Measured: 1 day

  5. Medication-fasting basal levels of cortisol precursors

    Levels in blood samples

    Measured: 1 day

  6. Medication-fasting basal levels of cortisol precursors

    Levels in urine samples

    Measured: 1 day

  7. Medication-fasting basal levels of cortisol precursors

    Levels in hair samples

    Measured: 1 day

  8. Medication-fasting basal levels of cortisol metabolites

    Levels in blood samples

    Measured: 1 day

  9. Medication-fasting basal levels of cortisol metabolites

    Levels in urine samples

    Measured: 1 day

  10. Medication-fasting basal levels of cortisol metabolites

    Levels in hair samples

    Measured: 1 day

  11. Medication-fasting basal levels of aldosterone

    Levels in blood samples

    Measured: 1 day

  12. Medication-fasting basal levels of aldosterone

    Levels in urine samples

    Measured: 1 day

  13. Medication-fasting basal levels of aldosterone precursors

    Levels in blood samples

    Measured: 1 day

  14. Medication-fasting basal levels of aldosterone precursors

    Levels in urine samples

    Measured: 1 day

  15. Medication-fasting basal levels of aldosterone metabolites

    Levels in blood samples

    Measured: 1 day

  16. Medication-fasting basal levels of aldosterone metabolites

    Levels in urine samples

    Measured: 1 day

  17. Medication-fasting basal levels of renin in patients with and without residual function.

    Levels in blood samples

    Measured: 1 day

  18. Medication-fasting basal levels of renin in patients with and without residual function.

    Levels in urine samples

    Measured: 1 day

  19. Medication-fasting basal levels of ACTH in patients with and without residual function.

    Levels in blood samples

    Measured: 1 day

  20. Medication-fasting basal levels of ACTH in patients with and without residual function.

    Levels in urine samples

    Measured: 1 day

  21. Medication-fasting basal levels of metanephrines in patients with and without residual function

    Levels in blood samples

    Measured: 1 day

  22. Medication-fasting basal levels of metanephrines in patients with and without residual function

    Levels in urine samples

    Measured: 1 day

  23. Medication-fasting ACTH-stimulated levels of cortisol

    Levels in blood samples

    Measured: 1 day

  24. Medication-fasting ACTH-stimulated levels of cortisol precursors

    Levels in blood samples

    Measured: 1 day

  25. Medication-fasting ACTH-stimulated levels of cortisol metabolites

    Levels in blood samples

    Measured: 1 day

  26. Medication-fasting ACTH-stimulated levels of aldosterone

    Levels in blood samples

    Measured: 1 day

  27. Medication-fasting ACTH-stimulated levels of aldosterone precursors

    Levels in blood samples

    Measured: 1 day

  28. Medication-fasting ACTH-stimulated levels of aldosterone metabolites

    Levels in blood samples

    Measured: 1 day

  29. Cortisol replacement doses, including stress doses in patients with and without residual function.

    Total daily dosage

    Measured: 1 day

  30. Cortisol stress doses in patients with and without residual function.

    No. stress doses the last week

    Measured: 1 day

  31. Fludrocortisone replacement doses in patients with and without residual function.

    Total daily dosage.

    Measured: 1 day

  32. In patients with and without residual function: disease-specific quality-of-life

    Total score ranging from 30 to 120 in disease-specific quality-of-life questionnaire, Addison Quality of Life (AddiQoL). For every question, scoring is translated in points (1 = 1 point, 2 and 3 = 2 points, 4 and 5 = 3 points, 6 = 4 points) and the algebraic sum of points is calculated. A higher score reflects better health-related quality-of-life.

    Measured: 1 day

  33. In patients with and without residual function, generic health-related quality of life by the Short Form (36) Health Survey

    The Short Form (36) Health Survey is a generic tool comprising 36 items evaluating patient reported quality of life concerning eight domains (physical functioning, role functioning physical, bodily pain, general health perception, vitality, social functioning, role functioning emotional, and mental health and general perception of change in health). Scores are expressed on a 0-100 scale with higher scores associated with better quality of life. The result of each domain is presented separately.

    Measured: 1 day

  34. Number of adrenal crises pr. 100 patient years

    Number of crises pr. 100 patient years for all included patients as well as in patients with versus without residual adrenal function

    Measured: 1 day

Timeline

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

  1. First posted4 Jan 2019
  2. Study start26 Sep 2018
  3. Primary completion31 Dec 2029 (estimated)
  4. Study completion31 Dec 2029 (estimated)

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 N/A
Primary purpose
Screening
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03793114
Sponsor's protocol ID
2018/751/REK sør-øst A (REK)
Status last verified
May 2026
First submitted
6 Nov 2018
Last updated
8 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Upon informed and signed content, biological samples will be stored in the biobank for research on endocrine disorders. Any new analyses will not be performed without approval from the Regional committee for medical and health research ethics.

Publications

  • Saevik AB, Akerman AK, Methlie P, Quinkler M, Jorgensen AP, Hoybye C, Debowska AJ, Nedrebo BG, Dahle AL, Carlsen S, Tomkowicz A, Sollid ST, Nermoen I, Gronning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Valland SF, Wahlberg J, Holte SE, Simunkova K, Kampe O, Husebye ES, Bensing S, Oksnes M. Residual Corticosteroid Production in Autoimmune Addison Disease. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2430-41. doi: 10.1210/clinem/dgaa256.

    PubMed 32392298

Questions about this trial

What is this clinical trial studying?

A study testing Cosyntropin stimulation test, Baseline blood tests and 30-hour ambulatory sampling of intestinal fluid in people with Primary Adrenal Insufficiency, run by University of Bergen at 3 sites in 3 countries.

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 5 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany, Norway, Sweden. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

The percentage of included patients with residual secretion of cortisol and aldosterone. (time frame: 1 day). 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 NCT03793114, which also lists 1 linked publication.

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 8 May 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in