Adrenal InsufficiencyPIANCT03410160
Predisposing Factors for the Incidence of Adrenal Crisis
An observational study of Adrenal Insufficiency, run by Wuerzburg University Hospital at 1 site in Germany.
Trial summary
Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- Clinical and biochemical examination.
- Type of treatment
- Pill or oral medicine
- How many people
- 71 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2015to Dec 2019
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with chronic adrenal insufficiency under hormone replacement therapy with glucocorticoids.
Who may be able to join
- Age >18 years
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Patients with chronic primary or secondary adrenal insufficiency under established stable replacement therapy (disease duration at least 2 years)
Who cannot join
- Age <18 years
- Pregnancy or breast feeding
- Intake of CYP3A4-inducting-drugs
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Wuerzburg, Dept. of medicine I
Würzburg, 97080
About this study
Official title: Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency
Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis.
Read the detailed description
Patients with chronic adrenal insufficiency (AI) are at risk of suffering from life-threatening adrenal crisis (AC), despite established hormone replacement therapies and patient education. Recent retrospective analyses observed different risk factors for AC, e.g. primary AI and comorbidities. Furthermore, patients that already experienced an AC seem to have an increased risk to develop further AC. The aim of the study is to evaluate potential risk factors/predisposing factors for AC in patients with chronic primary and secondary AI (PAI/SAI). Patients with chronic AI are assessed by clinical and biochemical examination and questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor. AI patients with a high frequency of AC will be compared to matched controls (age, sex and cause of AI) with no AC or a low frequency of AC in the past.
- Conditions
- Adrenal Insufficiency
- Being tested
- Clinical and biochemical examination.
- Keywords
- adrenal crisis, predisposing factors
- Medical subject headings
- Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical and biochemical examination.Diagnostic test
Patients with chronic adrenal insufficiency were assessed by clinical and biochemical examination as well as questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor.
| Study group | Role | What they receive |
|---|---|---|
| High frequency of adrenal crisis | Patients with a high frequency of adrenal crisis in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). Receives: Diagnostic Test: Clinical and biochemical examination. | |
| Low frequency of adrenal crisis | Patients with no adrenal crisis or a low frequency of AC in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). Receives: Diagnostic Test: Clinical and biochemical examination. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronic inflammation (hsCRP, Interleukin-6)
Measurement of hsCRP (mg/dl) and Interleukin-6 (pg/ml) levels. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit higher hsCRP and Interleukin-6 levels.
Measured: 1 day
Cortisol metabolism
Measurement of cortisol-levels (mg/dl) before as well as 60 min and 120 min after ingestion of hydrocortisone. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit a faster hydrocortisone metabolism.
Measured: 1 day
Replacement therapy with glucocorticoids
Evaluation of hormone replacement therapy with glucocorticoids by a clinical score. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.
Measured: 1 day
Replacement therapy with mineralocorticoids
Evaluation of hormone replacement therapy with mineralocorticoids by a clinical and biochemical assessment. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.
Measured: 1 day
Glucocorticoid-receptor-polymorphisms
Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a higher prevalence of glucocorticoid-receptor-polymorphisms.
Measured: 1 day
Catecholamine-levels
Evaluation of catecholamine-levels (ng/l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a more pronounced catecholamin-deficit.
Measured: 1 day
Patient education
Evaluation of patient education by questionnaire. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a worse education status.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2018
- Study startNov 2015
- Primary completionJun 2018
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefanie Hahner, MD, Prof., Principal investigator, Univesity Hospital Wuerzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03410160
- Sponsor's protocol ID
- PIA
- Acronym
- PIA
- Status last verified
- Oct 2019
- First submitted
- 18 Jan 2018
- Last updated
- 14 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
PubMed 25419882Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
PubMed 25288693Reisch N, Willige M, Kohn D, Schwarz HP, Allolio B, Reincke M, Quinkler M, Hahner S, Beuschlein F. Frequency and causes of adrenal crises over lifetime in patients with 21-hydroxylase deficiency. Eur J Endocrinol. 2012 Jul;167(1):35-42. doi: 10.1530/EJE-12-0161. Epub 2012 Apr 18.
PubMed 22513882Reincke M, Ritzel K, Osswald A, Berr C, Stalla G, Hallfeldt K, Reisch N, Schopohl J, Beuschlein F. A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M23-32. doi: 10.1530/EJE-15-0265. Epub 2015 May 20.
PubMed 25994948Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
PubMed 26208266Hahner S, Arlt W, Allolio B. [Adrenal crisis. Diagnostic and therapeutic management of acute adrenal cortex insufficiency]. Internist (Berl). 2003 Oct;44(10):1243-52. doi: 10.1007/s00108-003-1050-1. German.
PubMed 14689086
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency
- ClinicalTrials.gov ID
- NCT03410160
- Acronym / sponsor ID
- PIA / PIA
- Conditions
- Adrenal Insufficiency
- Keywords
- adrenal crisis, predisposing factors
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Study start
- Nov 2015 (actual)
- Primary completion
- Jun 2018 (actual)
- Study completion
- Dec 2019 (estimated)
- First posted
- 25 Jan 2018 (actual)
- 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.
Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis.
Detailed description
Patients with chronic adrenal insufficiency (AI) are at risk of suffering from life-threatening adrenal crisis (AC), despite established hormone replacement therapies and patient education. Recent retrospective analyses observed different risk factors for AC, e.g. primary AI and comorbidities. Furthermore, patients that already experienced an AC seem to have an increased risk to develop further AC. The aim of the study is to evaluate potential risk factors/predisposing factors for AC in patients with chronic primary and secondary AI (PAI/SAI). Patients with chronic AI are assessed by clinical and biochemical examination and questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor. AI patients with a high frequency of AC will be compared to matched controls (age, sex and cause of AI) with no AC or a low frequency of AC in the past.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High frequency of adrenal crisis | – | Diagnostic Test: Clinical and biochemical examination.Patients with a high frequency of adrenal crisis in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). |
| Low frequency of adrenal crisis | – | Diagnostic Test: Clinical and biochemical examination.Patients with no adrenal crisis or a low frequency of AC in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with chronic adrenal insufficiency under hormone replacement therapy with glucocorticoids.
Key inclusion criteria (4 listed)
- Age >18 years
- Patient´s written informed consent
- Ability to comply with the protocol procedures
- Patients with chronic primary or secondary adrenal insufficiency under established stable replacement therapy (disease duration at least 2 years)
Key exclusion criteria (3 listed)
- Age <18 years
- Pregnancy or breast feeding
- Intake of CYP3A4-inducting-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 |
|---|---|---|
| Clinical and biochemical examination.Patients with chronic adrenal insufficiency were assessed by clinical and biochemical examination as well as questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor. | Diagnostic test | High frequency of adrenal crisis, Low frequency of adrenal crisis |
Primary outcome
Chronic inflammation (hsCRP, Interleukin-6)
Time frame: 1 day
Measurement of hsCRP (mg/dl) and Interleukin-6 (pg/ml) levels. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit higher hsCRP and Interleukin-6 levels.
Cortisol metabolism
Time frame: 1 day
Measurement of cortisol-levels (mg/dl) before as well as 60 min and 120 min after ingestion of hydrocortisone. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit a faster hydrocortisone metabolism.
Replacement therapy with glucocorticoids
Time frame: 1 day
Evaluation of hormone replacement therapy with glucocorticoids by a clinical score. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.
Replacement therapy with mineralocorticoids
Time frame: 1 day
Evaluation of hormone replacement therapy with mineralocorticoids by a clinical and biochemical assessment. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement.
Glucocorticoid-receptor-polymorphisms
Time frame: 1 day
Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a higher prevalence of glucocorticoid-receptor-polymorphisms.
Catecholamine-levels
Time frame: 1 day
Evaluation of catecholamine-levels (ng/l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a more pronounced catecholamin-deficit.
Patient education
Time frame: 1 day
Evaluation of patient education by questionnaire. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a worse education status.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2019.
- Background: PubMed 25419882Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
- Background: PubMed 25288693Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
- Background: PubMed 22513882Reisch N, Willige M, Kohn D, Schwarz HP, Allolio B, Reincke M, Quinkler M, Hahner S, Beuschlein F. Frequency and causes of adrenal crises over lifetime in patients with 21-hydroxylase deficiency. Eur J Endocrinol. 2012 Jul;167(1):35-42. doi: 10.1530/EJE-12-0161. Epub 2012 Apr 18.
- Background: PubMed 25994948Reincke M, Ritzel K, Osswald A, Berr C, Stalla G, Hallfeldt K, Reisch N, Schopohl J, Beuschlein F. A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M23-32. doi: 10.1530/EJE-15-0265. Epub 2015 May 20.
- Background: PubMed 26208266Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
- Background: PubMed 14689086Hahner S, Arlt W, Allolio B. [Adrenal crisis. Diagnostic and therapeutic management of acute adrenal cortex insufficiency]. Internist (Berl). 2003 Oct;44(10):1243-52. doi: 10.1007/s00108-003-1050-1. German.
- Individual participant dataSharing planned: Undecided
Related trials for Adrenal Insufficiency
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Natural History Study of Patients With Excess Androgen
Congenital Adrenal Hyperplasia (CAH), Familial Male-Limited Precocious Puberty (FMPP)
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
Kidney Stiffness Measured by Ultrasound in Patients With High Blood Pressure and Healthy Volunteers
Arterial Hypertension, Chronic Kidney Disease, Primary Aldosteronism
Not yet recruiting
IT and IV Lentiviral Gene Therapy for X-ALD
X-linked Adrenoleukodystrophy
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.
Stefanie Hahner, MD, Prof. principal investigator
Univesity Hospital Wuerzburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adrenal Insufficiency, run by Wuerzburg University Hospital at 1 site in Germany.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 14 Oct 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 Germany. 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?
Results are not available in the source record.
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?
Chronic inflammation (hsCRP, Interleukin-6) (time frame: 1 day). The study lists 7 primary outcomes in all. 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 NCT03410160, which also lists 6 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 14 Oct 2019.