Adrenal InsufficiencyNCT03083834
Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients
A study testing Cosyntropin stimulation test in people with Adrenal Insufficiency and Adrenal Cancer, run by Bnai Zion Medical Center at 1 site in Israel.
Trial summary
In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases cortisol binding globulin levels (CBG), artificially raising total cortisol. Salivary free cortisol (SC) is not affected by CBG alterations, and reflects the free serum cortisol. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Adrenal Insufficiency, Adrenal Cancer
- What is being tested?
- Cosyntropin stimulation test
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- 14 Mar 2017to 31 Dec 2019
- 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- mitotane treated
- known hypoadrenlism
Who cannot join
- pregnancy
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Bnai Zion MC
Haifa
Leonard Saiegh, 506267262, leonard.saiegh@gmail.com
Michal Yeiches, 0528283062, yeiches@gmail.com
About this study
In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases cortisol binding globulin levels (CBG), artificially raising total cortisol. Salivary free cortisol (SC) is not affected by CBG alterations, and reflects the free serum cortisol.
In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.
Read the detailed description
80-90% of circulating cortisol is bound to cortisol binding globulin (CBG) or transcortin, whereas only 3-10% is in the free state. Salivary free cortisol (SC) is an index of plasma free cortisol. In previous studies it was shown that in low-dose cosyntropin stimulation test, SC increases significantly in normal but not in hypoadrenal patients. It was suggested that dynamic assessment of the SC response to ACTH may be particularly helpful whenever the measurement of serum cortisol is complicated by increased or decreased CBG levels.
Adrenocortical carcinoma (ACC) is a rare malignancy with a heterogeneous presentation and a variable but generally poor prognosis. Mitotane is the main drug for ACC treatment and it plays a role both in adjuvant treatment after complete resection and in recurrent, inoperable and/or metastatic ACC. Mitotane blocks adrenocortical steroid synthesis and also exerts a specific cytotoxic effect on adrenocortical cells. Mitotane induces adrenal insufficiency, requiring hydrocortisone replacement therapy. In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases CBG levels, artificially raising total cortisol. SC is not affected by CBG alterations, and reflects the free serum cortisol and may be more accurate in diagnosing hypoadrenalism in mitotane treated patients.
In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from any other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.
- Conditions
- Adrenal Insufficiency, Adrenal Cancer
- Being tested
- Cosyntropin stimulation test
- Keywords
- cosyntropin, salivary free cortisol, mitotane
- Medical subject headings
- Adrenal Insufficiency, Adrenal Gland Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cosyntropin stimulation testDiagnostic test
At 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later.
| Study group | Role | What they receive |
|---|---|---|
| healthy subjects | Experimental | low-dose cosyntropin stimulation test Receives: Diagnostic Test: Cosyntropin stimulation test |
| hypoadrenal mitotane treated patients | Experimental | low-dose cosyntropin stimulation test Receives: Diagnostic Test: Cosyntropin stimulation test |
| hypoadrenal no-mitotane treated patients | Experimental | low-dose cosyntropin stimulation test Receives: Diagnostic Test: Cosyntropin stimulation test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Salivary free cortisol
Salivary free cortisol concentrations during intravenous low dose cosyntropin stimulation test..
Measured: 1 day
Secondary outcomes (1)
serum cortisol
Serum cortisol concentrations during intravenous low dose cosyntropin stimulation test.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2017
- Study start14 Mar 2017
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bnai Zion Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, leonard.saiegh, Bnai Zion Medical Center
- Investigators
- Leonard Saiegh, MD, Principal investigator, Bnai Zion Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03083834
- Sponsor's protocol ID
- 0006-17-BNZ
- Status last verified
- Jan 2019
- First submitted
- 14 Mar 2017
- Last updated
- 18 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients
- ClinicalTrials.gov ID
- NCT03083834
- Acronym / sponsor ID
- 0006-17-BNZ
- Conditions
- Adrenal Insufficiency, Adrenal Cancer
- Keywords
- cosyntropin, salivary free cortisol, mitotane
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Bnai Zion Medical CenterOther government
- Study start
- 14 Mar 2017 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 20 Mar 2017 (actual)
- 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.
In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases cortisol binding globulin levels (CBG), artificially raising total cortisol. Salivary free cortisol (SC) is not affected by CBG alterations, and reflects the free serum cortisol.
In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.
Detailed description
80-90% of circulating cortisol is bound to cortisol binding globulin (CBG) or transcortin, whereas only 3-10% is in the free state. Salivary free cortisol (SC) is an index of plasma free cortisol. In previous studies it was shown that in low-dose cosyntropin stimulation test, SC increases significantly in normal but not in hypoadrenal patients. It was suggested that dynamic assessment of the SC response to ACTH may be particularly helpful whenever the measurement of serum cortisol is complicated by increased or decreased CBG levels.
Adrenocortical carcinoma (ACC) is a rare malignancy with a heterogeneous presentation and a variable but generally poor prognosis. Mitotane is the main drug for ACC treatment and it plays a role both in adjuvant treatment after complete resection and in recurrent, inoperable and/or metastatic ACC. Mitotane blocks adrenocortical steroid synthesis and also exerts a specific cytotoxic effect on adrenocortical cells. Mitotane induces adrenal insufficiency, requiring hydrocortisone replacement therapy. In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases CBG levels, artificially raising total cortisol. SC is not affected by CBG alterations, and reflects the free serum cortisol and may be more accurate in diagnosing hypoadrenalism in mitotane treated patients.
In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from any other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| healthy subjects | Experimental | Diagnostic Test: Cosyntropin stimulation testlow-dose cosyntropin stimulation test |
| hypoadrenal mitotane treated patients | Experimental | Diagnostic Test: Cosyntropin stimulation testlow-dose cosyntropin stimulation test |
| hypoadrenal no-mitotane treated patients | Experimental | Diagnostic Test: Cosyntropin stimulation testlow-dose cosyntropin stimulation test |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- mitotane treated
- known hypoadrenlism
Key exclusion criteria (1 listed)
- pregnancy
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 |
|---|---|---|
| Cosyntropin stimulation testAt 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later. | Diagnostic test | healthy subjects, hypoadrenal mitotane treated patients, hypoadrenal no-mitotane treated patients |
Primary outcome
Salivary free cortisol
Time frame: 1 day
Salivary free cortisol concentrations during intravenous low dose cosyntropin stimulation test..
1 secondary outcome
serum cortisol
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2019.
- 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.
Leonard Saiegh, MD principal investigator
Bnai Zion Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cosyntropin stimulation test in people with Adrenal Insufficiency and Adrenal Cancer, run by Bnai Zion Medical Center at 1 site in Israel.
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: status not confirmed, as of the sponsor's last update on 18 Jan 2019. 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 Israel. 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 Leonard Saiegh, MD (+972506267262, leonard.saiegh@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Salivary free cortisol (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jan 2019.