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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Haukeland University Hospital
Sponsor:
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT01504555
First received: November 15, 2011
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

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.


Condition Phase
Cushing's Syndrome
Adrenal Incidentalomas
Alcoholism
Obesity
Phase 3

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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).


  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A saliva cortisol cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.

  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.

  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A saliva cortisone cut-off level will be defined a priori from ROC analysis on all patients with and without Cushing's syndrome.

  • Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Compute a 95% confidence interval for morning s-DXM following overnight DXM-test in healthy subjects using parametric and non-parametric statistics. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Parametric descriptive statis

  • Evaluate the dexamethasone metabolism in patients with obesity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 supression test.

  • Evaluate the dexamethasone metabolism in patients with alcohol abuse [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 supression test.


Biospecimen Retention:   Samples Without DNA

Blood, saliva, urine


Estimated Enrollment: 300
Study Start Date: October 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Patients under investigation for hypercortisolism
Patients undergoing routine evaluation for hypercortisolism at Haukeland University Hospital, Bergen, Norway, will be asked to participate.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients at Haukeland University Hosptial, Bergen, Norway, under routine evaluation for hypercortisolism.Patients under evaluation for obeity at the overweight clinic, and Patients treated for alcohol abuse at the clinic for alcohol addicts at Haukeland University hospital.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504555

Contacts
Contact: Grethe Åstrøm Ueland, MD +4790950021 geas@helse-bergen.no
Contact: Paal Methli, MD +4797677930

Locations
Norway
Haukeland Universitetssykehus- Endokrinologisk avdeling Recruiting
Bergen, Norway, 5021
Contact: Grethe Åstrøm Ueland, Doctor    +4790950021    geas@helse-bergen.no   
Contact: Hrafnkell Baldur Thordarsson, Doctor    +4755972995    hraf@helse-bergen.no   
Principal Investigator: Grethe Ueland, MD         
Sub-Investigator: Hrafnkell Baldur Thordarsson, MD         
Sub-Investigator: Eystein Husebye, Prof.Dr.Med         
Sub-Investigator: Kristian Løvås, Prof.Dr.Med         
Haukeland University Hospital- Hormonlaboratory Recruiting
Bergen, Norway, 5096
Contact: Grethe Åstrøm Ueland, Doctor    +4790950021    geas@helse-bergen.no   
Contact: Paal Methli, Doctor    +4797677930      
Principal Investigator: Grethe Åstrøm Ueland, Doctor         
Sub-Investigator: Paal Methli, Doctor         
Institutt for farmakologi Recruiting
Bergen, Norway, 5021
Contact: Simon Steinar Hustad, Dr.Med         
Haukeland Universitetssykehus- Rusmedisinsk avdeling Not yet recruiting
Bergen, Norway, 5019
Contact: Pia Synøve Kloster, Cand.med    55975000      
Sub-Investigator: Pia Synøve Kloster, Cand.med         
Sponsors and Collaborators
Haukeland University Hospital
Investigators
Study Chair: Grethe Åstrøm Ueland, MD Haukeland University Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT01504555     History of Changes
Other Study ID Numbers: 2011/1810
Study First Received: November 15, 2011
Last Updated: December 10, 2012
Health Authority: Norway: Regional Ethics Commitee

Keywords provided by Haukeland University Hospital:
hypercortisolism, dexamethasone, alcoholism,obesity.

Additional relevant MeSH terms:
Adrenocortical Adenoma
Obesity
Syndrome
Alcoholism
Cushing Syndrome
Adrenal Gland Neoplasms
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Disease
Pathologic Processes
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Adrenal Cortex Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Adrenal Cortex Diseases
Dexamethasone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics

ClinicalTrials.gov processed this record on September 18, 2014