Cushing's SyndromeDXMNCT01504555
Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing's Syndrome?
An observational study of Cushing's Syndrome and Adrenal Incidentalomas, run by Haukeland University Hospital at 4 sites in Norway.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing's Syndrome, Adrenal Incidentalomas, Alcoholism
- How many people
- 300 participants
- Where
- 4 sitesNorway
- Study dates
- Oct 2011to Sep 2017
- 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 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.
Who may be able to join
- Age over 18 years
- Under investigation for hypercortisolism
- Able and willing to make informed consent
Who cannot join
- Use of systemic or local glucocorticoids
Trial locations and contacts
4 sites in 1 country.
Paal Methli, MD contact
Norway4 sites, 4 recruiting
- Not yet recruiting
Haukeland Universitetssykehus- Rusmedisinsk avdeling
Bergen, 5019
Pia Synøve Kloster, Cand.med, 55975000
Pia Synøve Kloster, Cand.med
- Recruiting
Haukeland Universitetssykehus- Endokrinologisk avdeling
Bergen, 5021
Grethe Åstrøm Ueland, Doctor, +4790950021, geas@helse-bergen.no
Hrafnkell Baldur Thordarsson, Doctor, +4755972995, hraf@helse-bergen.no
- Recruiting
Institutt for farmakologi
Bergen, 5021
Simon Steinar Hustad, Dr.Med
- Recruiting
Haukeland University Hospital- Hormonlaboratory
Bergen, 5096
Grethe Åstrøm Ueland, Doctor, +4790950021, geas@helse-bergen.no
Paal Methli, Doctor, +4797677930
About this study
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
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.
Read more
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.
- Conditions
- Cushing's Syndrome, Adrenal Incidentalomas, Alcoholism, Obesity
- Keywords
- hypercortisolism, dexamethasone, alcoholism,obesity.
- Medical subject headings
- Cushing Syndrome, Adrenal incidentaloma, Alcoholism, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients under investigation for hypercortisolism | Patients undergoing routine evaluation for hypercortisolism at Haukeland University Hospital, Bergen, Norway, will be asked to participate. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (15)
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).
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM.
Measured: 1 year
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol.
Measured: 1 year
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
Compute a 95% confidence interval for morning s-DXM following overnight DXM-test in healthy subjects using parametric and non-parametric statistics.
Measured: 1 year
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
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2012 (estimated)
- Study startOct 2011
- Primary completionSep 2017 (estimated)
- Study completionSep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cushing's SyndromeStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- 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 only
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Grethe Åstrøm Ueland, MD, Study chair, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01504555
- Sponsor's protocol ID
- 2011/1810
- Acronym
- DXM
- Status last verified
- Sep 2016
- First submitted
- 15 Nov 2011
- Last updated
- 26 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19602562Nieman 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.
PubMed 18334580Carroll 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.
PubMed 20821267
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01504555
- Acronym / sponsor ID
- DXM / 2011/1810
- Conditions
- Cushing's Syndrome, Adrenal Incidentalomas, Alcoholism, Obesity
- Keywords
- hypercortisolism, dexamethasone, alcoholism,obesity.
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 5 Jan 2012 (estimated)
- 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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients under investigation for hypercortisolism | – | –Patients undergoing routine evaluation for hypercortisolism at Haukeland University Hospital, Bergen, Norway, will be asked to participate. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- Age over 18 years
- Under investigation for hypercortisolism
- Able and willing to make informed consent
Key exclusion criteria (1 listed)
- Use of systemic or local glucocorticoids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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.
15 secondary outcomes
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
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
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
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
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
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
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM.
Time frame: 1 year
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM, and saliva-cortisol replace serum-cortisol.
Time frame: 1 year
Identical to primary endpoint, but saliva-DXM measurements replace serum-DXM and saliva-cortisone replace serum-cortisol.
Time frame: 1 year
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
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
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
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
Evaluate the dexamethasone metabolism in patients with obesity
Time frame: 1 year
Evaluate the dexamethasone metabolism in patients with alcohol abuse
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2016.
- Background: PubMed 19602562Baid 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.
- Background: PubMed 18334580Nieman 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.
- Background: PubMed 20821267Carroll 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.
- Kortisol i spytt ved sykdom i binyreneLink provided by the sponsor.
- Spyttprøver til kortisolmålingLink provided by the sponsor.
- Endogent Cushing syndromLink provided by the sponsor.
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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.
Paal Methli, MD contact
Grethe Åstrøm Ueland, MD study chair
Haukeland University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cushing's Syndrome and Adrenal Incidentalomas, run by Haukeland University Hospital at 4 sites in Norway.
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 3 inclusion and 1 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 26 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Norway. 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?
Contact Grethe Åstrøm Ueland, MD (+4790950021, geas@helse-bergen.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 NCT01504555, which also lists 3 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 26 Sep 2016.