Adrenal InsufficiencyNCT02818660
Mass Spectrometry Based Cutoffs for Cortisol After Stimulation Tests
A study testing Synachten in people with Adrenal Insufficiency, run by Haukeland University Hospital at 1 site in Norway.
Trial summary
There are two main stimulation tests used to decide if a patient has cortisol deficiency. It is the "synacthen test", were we stimulate the patient with intramuscular or intravenous synacthen ( ACTH) to see how much cortisol the adrenals are capable of producing, and it is the "Insulin hypoglycemia test" were we give… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- Synachten
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 232 participants
- Where
- 1 siteNorway
- Study dates
- 21 May 2016to 21 Dec 2017
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy individuals not using any corticosteroids .
- Patients with clinical suspicion of primary or secondary adrenal insufficiency. -Patient suspicious of having an enzyme defect ( 21 hydroxylase deficiency) giving hirsutism.
Who cannot join
- -Use of corticosteroids.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mass Spectrometry Based Cutoffs for Cortisol and 17-hydroxy-progesterone (17-OH-progesterone) After Stimulation Tests for Primary and Secondary Adrenal Insufficiency.
There are two main stimulation tests used to decide if a patient has cortisol deficiency. It is the "synacthen test", were we stimulate the patient with intramuscular or intravenous synacthen ( ACTH) to see how much cortisol the adrenals are capable of producing, and it is the "Insulin hypoglycemia test" were we give the patient insulin to provoke a hypoglycemia, and look at the adrenal response to that stimulus. The cut off values for a normal response is based on old immunological assays no longer in use. Assays with a lot of interference and cross reactivity leading to measurement of higher values for cortisol than what we measure on the highly specific LCMS/MS ( Liquid chromatography mass spectrometry methode) that we are using for cortisol today. So, there is a need for new cut off values for a normal response to such tests. The purpose of this study is to produce such new cutoff values by performing the test in 120 healthy controls. We also want to perform the test in patient groups normally going trough this tests according to the same protocol as the control persons, to evaluate the new cutoffs in different patient groups.
Read the detailed description
120 healthy controls will perform an intravenous synacthen test in our out patient clinic. We register anthropometric data, and take basal blood screening to assure they are healthy. We take basal blood and saliva samples right before start of the test ( called 0-samples). Then they get intravenous synacthen, and we take new samples at 30 minutes and 60 minutes. They are observed during the procedure. We will then calculate a new cut off value for cortisol after the test, based on the 2.5 percentile for cortisol in this population. We will also calculate the same for 17-OH-progesterone, a parameter we also look at after synacthen test in som patient groups ( patients with hirsutism, who are suspicious of having an enzyme defect in the cortisol synthesis cascade). The saliva samples will also be analyzed for cortisol and 17-OH-progesterone, to evaluate if it is possible to use saliva instead of blood samples in synacthen tests in the future. The advantage of using saliva samples is that they can be used also in patients with elevated amount of cortisol binding globulin (CBG), because it measure the free hormone that is biological active ( not both the free and the protein bound, as we measure in serum samples). This is important in patients on estrogens , and in pregnant women, that have large amount of CBG.
- Conditions
- Adrenal Insufficiency
- Being tested
- Synachten
- Medical subject headings
- Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SynachtenDrug
Also called tetracosactide
To stimulate the adrenals to increase the cortisol Production as much as possible
| Study group | Role | What they receive |
|---|---|---|
| Synacthen | Experimental | The patient get Synacthen to stimulate the adrenals to produce cortisol Receives: Drug: Synachten |
What is being measured
The primary outcome is the main question the study is designed to answer.
Define a cutoff level for serum cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.
s-cortisol
Measured: 2 year
Secondary outcomes (3)
Define a cutoff level for serum 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.
s-17-OH-progesterone
Measured: 2 year
Define a cutoff level for saliva cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.
saliva cortisol
Measured: 2 year
Define a cutoff level for saliva 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.
saliva 17-OH-progesterone
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start21 May 2016
- Primary completion21 Dec 2017
- Study completion21 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Grethe Åstrøm Ueland, MD, Principal investigator, Haukeland University Hopsital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02818660
- Sponsor's protocol ID
- 2016/174
- Status last verified
- Feb 2024
- First submitted
- 14 Jun 2016
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ueland GA, Methlie P, Oksnes M, Thordarson HB, Sagen J, Kellmann R, Mellgren G, Raeder M, Dahlqvist P, Dahl SR, Thorsby PM, Lovas K, Husebye ES. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1696-1703. doi: 10.1210/jc.2017-02602.
PubMed 29452421Ueland GA, Dahl SR, Methlie P, Hessen S, Husebye ES, Thorsby PM. Adrenal steroid profiling as a diagnostic tool to differentiate polycystic ovary syndrome from nonclassic congenital adrenal hyperplasia: pinpointing easy screening possibilities and normal cutoff levels using liquid chromatography tandem mass spectrometry. Fertil Steril. 2022 Aug;118(2):384-391. doi: 10.1016/j.fertnstert.2022.05.012. Epub 2022 Jun 18.
PubMed 35725670
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mass Spectrometry Based Cutoffs for Cortisol and 17-hydroxy-progesterone (17-OH-progesterone) After Stimulation Tests for Primary and Secondary Adrenal Insufficiency.
- ClinicalTrials.gov ID
- NCT02818660
- Acronym / sponsor ID
- 2016/174
- Conditions
- Adrenal Insufficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 21 May 2016 (actual)
- Primary completion
- 21 Dec 2017 (actual)
- Study completion
- 21 Dec 2017 (actual)
- First posted
- 30 Jun 2016 (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.
There are two main stimulation tests used to decide if a patient has cortisol deficiency. It is the "synacthen test", were we stimulate the patient with intramuscular or intravenous synacthen ( ACTH) to see how much cortisol the adrenals are capable of producing, and it is the "Insulin hypoglycemia test" were we give the patient insulin to provoke a hypoglycemia, and look at the adrenal response to that stimulus. The cut off values for a normal response is based on old immunological assays no longer in use. Assays with a lot of interference and cross reactivity leading to measurement of higher values for cortisol than what we measure on the highly specific LCMS/MS ( Liquid chromatography mass spectrometry methode) that we are using for cortisol today. So, there is a need for new cut off values for a normal response to such tests. The purpose of this study is to produce such new cutoff values by performing the test in 120 healthy controls. We also want to perform the test in patient groups normally going trough this tests according to the same protocol as the control persons, to evaluate the new cutoffs in different patient groups.
Detailed description
120 healthy controls will perform an intravenous synacthen test in our out patient clinic. We register anthropometric data, and take basal blood screening to assure they are healthy. We take basal blood and saliva samples right before start of the test ( called 0-samples). Then they get intravenous synacthen, and we take new samples at 30 minutes and 60 minutes. They are observed during the procedure. We will then calculate a new cut off value for cortisol after the test, based on the 2.5 percentile for cortisol in this population. We will also calculate the same for 17-OH-progesterone, a parameter we also look at after synacthen test in som patient groups ( patients with hirsutism, who are suspicious of having an enzyme defect in the cortisol synthesis cascade). The saliva samples will also be analyzed for cortisol and 17-OH-progesterone, to evaluate if it is possible to use saliva instead of blood samples in synacthen tests in the future. The advantage of using saliva samples is that they can be used also in patients with elevated amount of cortisol binding globulin (CBG), because it measure the free hormone that is biological active ( not both the free and the protein bound, as we measure in serum samples). This is important in patients on estrogens , and in pregnant women, that have large amount of CBG.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Synacthen | Experimental | Drug: SynachtenThe patient get Synacthen to stimulate the adrenals to produce cortisol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy individuals not using any corticosteroids .
- Patients with clinical suspicion of primary or secondary adrenal insufficiency. -Patient suspicious of having an enzyme defect ( 21 hydroxylase deficiency) giving hirsutism.
Key exclusion criteria (1 listed)
- -Use of corticosteroids.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SynachtenAlso: tetracosactideTo stimulate the adrenals to increase the cortisol Production as much as possible | Drug | Synacthen |
Primary outcome
Define a cutoff level for serum cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.
Time frame: 2 year
s-cortisol
3 secondary outcomes
Define a cutoff level for serum 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.
Time frame: 2 year
Define a cutoff level for saliva cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.
Time frame: 2 year
Define a cutoff level for saliva 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.
Time frame: 2 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Results publication: PubMed 29452421Ueland GA, Methlie P, Oksnes M, Thordarson HB, Sagen J, Kellmann R, Mellgren G, Raeder M, Dahlqvist P, Dahl SR, Thorsby PM, Lovas K, Husebye ES. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1696-1703. doi: 10.1210/jc.2017-02602.
- Results publication: PubMed 35725670Ueland GA, Dahl SR, Methlie P, Hessen S, Husebye ES, Thorsby PM. Adrenal steroid profiling as a diagnostic tool to differentiate polycystic ovary syndrome from nonclassic congenital adrenal hyperplasia: pinpointing easy screening possibilities and normal cutoff levels using liquid chromatography tandem mass spectrometry. Fertil Steril. 2022 Aug;118(2):384-391. doi: 10.1016/j.fertnstert.2022.05.012. Epub 2022 Jun 18.
- Individual participant dataSharing planned: No
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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.
Grethe Åstrøm Ueland, MD principal investigator
Haukeland University Hopsital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Synachten in people with Adrenal Insufficiency, run by Haukeland University Hospital at 1 site 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 2 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: finished, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define a cutoff level for serum cortisol after stimulation with synacthen or hypoglycemia in healthy control persons. (time frame: 2 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 NCT02818660, which also lists 2 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 1 Mar 2024.