Predisposing Factors for the Incidence of Adrenal Crisis (PIA)

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ClinicalTrials.gov Identifier: NCT03410160

Recruitment Status : Active, not recruiting

First Posted : January 25, 2018

Last Update Posted : October 14, 2019

Sponsor:

Information provided by (Responsible Party):

Wuerzburg University Hospital

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Adrenal Insufficiency	Diagnostic Test: Clinical and biochemical examination.

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

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Study Type :	Observational
Estimated Enrollment :	71 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency
Actual Study Start Date :	November 2015
Actual Primary Completion Date :	June 2018
Estimated Study Completion Date :	December 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial glucocorticoid deficiency

Drug Information available for: Epinephrine bitartrate Epinephrine Epinephrine hydrochloride Racepinephrine hydrochloride Racepinephrine

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
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).	Diagnostic Test: 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.
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).	Diagnostic Test: 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.

Outcome Measures

Primary Outcome Measures :

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.

Biospecimen Retention: Samples With DNA

Retention of samples with and without DNA (whole-blood and serum).

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients with chronic adrenal insufficiency under hormone replacement therapy with glucocorticoids.

Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

Age <18 years
Pregnancy or breast feeding
Intake of CYP3A4-inducting-drugs

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410160

Locations

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Germany
University Hospital Wuerzburg, Dept. of medicine I
Wuerzburg, Germany, 97080

Sponsors and Collaborators

Wuerzburg University Hospital

Investigators

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Principal Investigator:	Stefanie Hahner, MD, Prof.	Univesity Hospital Wuerzburg

More Information

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.

Allolio 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. Review.

Reisch 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.

Reincke 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. Review.

Smans 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.

Hahner S, Arlt W, Allolio B. [Adrenal crisis. Diagnostic and therapeutic management of acute adrenal cortex insufficiency]. Internist (Berl). 2003 Oct;44(10):1243-52. Review. German.

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Responsible Party:	Wuerzburg University Hospital
ClinicalTrials.gov Identifier:	NCT03410160
Other Study ID Numbers:	PIA
First Posted:	January 25, 2018 Key Record Dates
Last Update Posted:	October 14, 2019
Last Verified:	October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Wuerzburg University Hospital:


adrenal crisis predisposing factors

Additional relevant MeSH terms:

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Adrenal Insufficiency Adrenal Gland Diseases Endocrine System Diseases

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