Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03793114
Other study ID # 2018/751/REK sør-øst A (REK)
Secondary ID
Status Active, not recruiting
Phase N/A
First received
Last updated
Start date September 26, 2018
Est. completion date December 2025

Study information

Verified date November 2023
Source University of Bergen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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?


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 200
Est. completion date December 2025
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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.

Study Design


Intervention

Diagnostic Test:
Cosyntropin 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 tests
Medication-fasting morning levels of adrenocortical hormones.
Device:
30-hour ambulatory sampling of intestinal fluid
30-hour ambulatory sampling of intestinal fluid for analysis of adrenocortical hormones.
Other:
Blood test
Cardiovascular and inflammatory biomarker profiles

Locations

Country Name City State
Germany Endokrinologie in Charlottenburg Berlin
Norway Haukeland University Hospital Bergen
Sweden Karolinska Institutet Stockholm

Sponsors (3)

Lead Sponsor Collaborator
University of Bergen Charite University, Berlin, Germany, Karolinska Institutet

Countries where clinical trial is conducted

Germany,  Norway,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Other Adrenocortical hormones in congenital adrenal hyperplasia (CAH) controls Presence or absence of adrenocortical hormones in congenital adrenal hyperplasia (CAH) controls in a medication fasting morning baseline blood sample 1 day
Other Adrenocortical hormones in bilaterally adrenalectomized controls Presence or absence of adrenocortical hormones in bilaterally adrenalectomized controls in a medication fasting morning baseline blood sample 1 day
Other Change in response to cosyntropin testing Response to cosyntropin testing at 3, 6, 12, and 24 months after diagnosis 4 days
Other Diurnal variation in adrenocortical hormone secretion Variation in endogenous adrenocortical hormone secretion during 30 hour continuous sampling 2 days
Primary The percentage of included patients with residual secretion of cortisol and aldosterone. Percentage of included patients with detectable levels of adrenal steroid hormones. 1 day
Secondary Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines Levels in blood samples 1 day
Secondary Medication-fasting basal levels of cortisol Levels in blood samples 1 day
Secondary Medication-fasting basal levels of cortisol Levels in urine samples 1 day
Secondary Medication-fasting basal levels of cortisol Levels in hair samples 1 day
Secondary Medication-fasting basal levels of cortisol precursors Levels in blood samples 1 day
Secondary Medication-fasting basal levels of cortisol precursors Levels in urine samples 1 day
Secondary Medication-fasting basal levels of cortisol precursors Levels in hair samples 1 day
Secondary Medication-fasting basal levels of cortisol metabolites Levels in blood samples 1 day
Secondary Medication-fasting basal levels of cortisol metabolites Levels in urine samples 1 day
Secondary Medication-fasting basal levels of cortisol metabolites Levels in hair samples 1 day
Secondary Medication-fasting basal levels of aldosterone Levels in blood samples 1 day
Secondary Medication-fasting basal levels of aldosterone Levels in urine samples 1 day
Secondary Medication-fasting basal levels of aldosterone precursors Levels in blood samples 1 day
Secondary Medication-fasting basal levels of aldosterone precursors Levels in urine samples 1 day
Secondary Medication-fasting basal levels of aldosterone metabolites Levels in blood samples 1 day
Secondary Medication-fasting basal levels of aldosterone metabolites Levels in urine samples 1 day
Secondary Medication-fasting basal levels of renin in patients with and without residual function. Levels in blood samples 1 day
Secondary Medication-fasting basal levels of renin in patients with and without residual function. Levels in urine samples 1 day
Secondary Medication-fasting basal levels of ACTH in patients with and without residual function. Levels in blood samples 1 day
Secondary Medication-fasting basal levels of ACTH in patients with and without residual function. Levels in urine samples 1 day
Secondary Medication-fasting basal levels of metanephrines in patients with and without residual function Levels in blood samples 1 day
Secondary Medication-fasting basal levels of metanephrines in patients with and without residual function Levels in urine samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of cortisol Levels in blood samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of cortisol precursors Levels in blood samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of cortisol metabolites Levels in blood samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of aldosterone Levels in blood samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of aldosterone precursors Levels in blood samples 1 day
Secondary Medication-fasting ACTH-stimulated levels of aldosterone metabolites Levels in blood samples 1 day
Secondary Cortisol replacement doses, including stress doses in patients with and without residual function. Total daily dosage 1 day
Secondary Cortisol stress doses in patients with and without residual function. No. stress doses the last week 1 day
Secondary Fludrocortisone replacement doses in patients with and without residual function. Total daily dosage. 1 day
Secondary 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. 1 day
Secondary 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. 1 day
Secondary 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 1 day
See also
  Status Clinical Trial Phase
Completed NCT05222152 - Chronocort Versus Plenadren Replacement Therapy in Adults With Adrenal Insufficiency Phase 2
Completed NCT01450930 - Pharmacokinetics of Hydrocortisone After Subcutaneous Administration in Chronic Adrenal Insufficiency Phase 2
Not yet recruiting NCT06299020 - Risks of Intermittent Fasting in Patients With Primary Adrenal Insufficiency N/A
Completed NCT02277587 - Dual RElease Hydrocortisone Versus conventionAl Glucocorticoid replaceMent Therapy in Hypocortisolism (DREAM) Phase 4