Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome?

Obesity Clinical Trial

— DXM  

Official title:

Evaluation of the Diagnostic Utility of Serum Dexamethasone Measurements in the Overnight 1mg Dexamethasone Suppression Test in Patients Investigated for Cushing's Syndrome and Incidentalomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01504555
• Other study ID #: 2011/1810
• Status: Recruiting
• Phase: Phase 3
• First received: November 15, 2011
• Last updated: September 23, 2016
• Start date: October 2011
• Est. completion date: September 2017

Study information

• Verified date: September 2016
• Source: Haukeland University Hospital
• Contact: Grethe Åstrøm Ueland, MD
• Phone: +4790950021
• Email: geas[@]helse-bergen.no
• Is FDA regulated: No
• Health authority: Norway: Regional Ethics Commitee
• Study type: Observational

Clinical Trial Summary

Background: The evaluation for hypercortisolism includes an overnight 1mg dexamethasone (DXM) suppression test. An important shortcoming is the diagnostic specificity of only 80%, which is likely due to inter-individual differences in gut absorption or metabolism of DXM.

Study hypothesis: The investigators hypothesize that serum-DXM measurements will increase the diagnostic accuracy of the overnight DXM-test in the work-up of hypercortisolism.

Aims: The primary aim of this prospective study is to evaluate if serum-DXM measured simultaneously with serum-cortisol in morning samples could increase the diagnostic accuracy this diagnostic test. There are several secondary aims. One is to estimate the prevalence and causes of unusual DXM absorption or metabolism. The investigators will also evaluate the feasibility and diagnostic accuracy of salivary DXM. Moreover, the diagnostic accuracy of midnight salivary cortisol and cortisone, and urinary cortisol, will be evaluated and compared.

Design: Levels of DXM in morning serum following an overnight DXM-test will be analyzed in patients under evaluation for hypercortisolism (including incidentalomas). A cut-off level to identify inadequate DXM concentrations in serum to suppress endogenous cortisol production will be established based on the negative tests. This cut-off level will then be applied in a retrospective analysis of the diagnostic accuracy of DXM-tests. This prospective study has a blinded design as the DXM measurements are disclosed after the end of the trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age over 18 years

• Under investigation for hypercortisolism

• Able and willing to make informed consent

Exclusion Criteria:

• Use of systemic or local glucocorticoids

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Adrenal Incidentalomas
• Adrenocortical Adenoma
• Alcoholism
• Cushing Syndrome
• Cushing's Syndrome
• Obesity
• Syndrome

Locations

Country	Name	City	State
Norway	Haukeland Universitetssykehus- Endokrinologisk avdeling	Bergen
Norway	Haukeland Universitetssykehus- Rusmedisinsk avdeling	Bergen
Norway	Haukeland University Hospital- Hormonlaboratory	Bergen
Norway	Institutt for farmakologi	Bergen

Sponsors (1)

Lead Sponsor	Collaborator
Haukeland University Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (3)

Baid SK, Rubino D, Sinaii N, Ramsey S, Frank A, Nieman LK. Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J Clin Endocrinol Metab. 2009 Oct;94(10):3857-64. doi: 10.1210/jc.2008-2766. Epub 2009 Jul 14. — View Citation

Carroll TB, Findling JW. The diagnosis of Cushing's syndrome. Rev Endocr Metab Disord. 2010 Jun;11(2):147-53. doi: 10.1007/s11154-010-9143-3. Review. — View Citation

Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125. Epub 2008 Mar 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference (in percent) in false positive DXM-tests comparing the outcome of all tests with all tests excluding those with s-DXM below the the cut-off specified below.	The s-DXM cut-off will be defined a priori from ROC analysis on patients that inadequately suppress s-cortisol categorized as having Cushing's syndrome or being healthy.; DXM, dexamethasone; DXM-test, short 1mg dexamethasone suppression test.	1 year	No
Secondary	Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for the short DXM-test in the assessment of Cushing's syndrome (CS), after excluding those with s-DXM below the DXM cut-off specified in the primary endpoint.	Sensitivity = (Number of patients having CS with positive test / total number of patients with CS).; Specificity = (Number of patients not having CS with negative test / total number of patients not having CS).	1 year	No
Secondary	Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for the short DXM-test in the assessment of Cushing's syndrome, after excluding those with s-DXM below the DXM cut-off specified in the primary endpoint.		1 year	No
Secondary	Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisol in the assessment of Cushing's syndrome. All study cases are included in this analysis.		1 year	No
Secondary	Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisol in the assessment of Cushing's syndrome. All study cases are included in this analysis.	A saliva cortisol cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.	1 year	No
Secondary	Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisone in the assessment of Cushing's syndrome. All study cases are included in this analysis.	A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.	1 year	No
Secondary	Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for midnight salivary cortisone in the assessment of Cushing's syndrome. All study cases are included in this analysis.	A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.	1 year	No
Secondary	Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM.		1 year	No
Secondary	Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol.		1 year	No
Secondary	Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol.		1 year	No
Secondary	Calculate the positive likelihood ratio [(1-sensitivity)/specificity] for creatinine-adjusted cortisol in morning spot urine in the assessment of Cushing's syndrome. All study cases are included in this analysis.	A cut-off level for creatinine-adjusted morning urine cortisol will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.	1 year	No
Secondary	Calculate the negative likelihood ratio [(1-sensitivity)/specificity] for creatinine-adjusted cortisol in morning spot urine in the assessment of Cushing's syndrome. All study cases are included in this analysis.	A cut-off level for creatinine-adjusted morning urine cortisol will be defined a priori from ROC analysis on all patients with and without Cushing's Syndrome.	1 year	No
Secondary	Compute a 95% confidence interval for morning s-DXM following overnight DXM-test in healthy subjects using parametric and non-parametric statistics.		1 year	No
Secondary	Quantitatively and qualitatively describe the characteristics of patients with false positive DXM-test and true negative DXM-test based on a standard questionnaire scoring patient history, symptoms and clinical features.	Parametric descriptive statistics	1 year	No
Secondary	Evaluate the dexamethasone metabolism in patients with obesity	We are evaluating if overweight patients metabolise Dexamethasone in the same way as normal weighted patients, by looking at the s-dexamethasone and s-cortisol level the day after 1 mg overnight Dexamethason suppression test.	1 year	No
Secondary	Evaluate the dexamethasone metabolism in patients with alcohol abuse	We are evaluating if patients with alcohol abuse metabolise dexamethasone in the same way as normal patients, by looking at the s-dexamethasone and s-cortisol level the day after 1 mg overnight dexamethason suppression test.	1 year	No

External Links

•   Endogent Cushing syndrom
•   Kortisol i spytt ved sykdom i binyrene
•   Spyttprøver til kortisolmåling