Predisposing Factors for the Incidence of Adrenal Crisis

Adrenal Insufficiency Clinical Trial

— PIA  

Official title:

Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03410160
• Other study ID #: PIA
• Status: Active, not recruiting
• Start date: November 2015
• Est. completion date: December 2019

Study information

• Verified date: October 2019
• Source: Wuerzburg University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: December 2019
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adrenal Insufficiency

Intervention

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.

Locations

Country	Name	City	State
Germany	University Hospital Wuerzburg, Dept. of medicine I	Wuerzburg

Sponsors (1)

Lead Sponsor	Collaborator
Wuerzburg University Hospital

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 day
Primary	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.	1 day
Primary	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.	1 day
Primary	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.	1 day
Primary	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.	1 day
Primary	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.	1 day
Primary	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.	1 day