Adrenal Hyperplasia, CongenitalEVAF-21NCT01862380
Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency.
A study testing Functional explorations in people with Adrenal Hyperplasia, Congenital and 21-hydroxylase Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The risk of adrenal insufficiency in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is not well documented. Indication of cortisol replacement therapy in situation of acute stress or at long term is thus controversial. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Adrenal Hyperplasia, Congenital, 21-hydroxylase Deficiency
- What is being tested?
- Functional explorations
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2013to Nov 2016
- 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 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Groupe of patients:
- women aged 18-50 years with nonclassical 21-hydroxylase deficiency with homozygous or compound heterozygous mutations of CYP21A2 and plasma 17-hydroxyprogesterone concentration after stimulation with synacthen >= 10ng/mL
- Groupe of healthy volunteers :
- age matched female healthy volunteers with plasma 17-hydroxyprogesterone concentration after stimulation with synacthen < 2ng/mL
Who cannot join
- treatment with oral or local glucocorticoids < 1 year
- oral estroprogestative contraception < 3 months
- spironolactone < 3 months
- cyproterone acetate < 3 months
- treatment modifying the activity of the renin - angiotensine - aldosterone system < 2 weeks
- pregnancy and lactation
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital
Le Kremlin-Bicêtre, 94 275
About this study
Official title: Evaluation of Adrenocortical Functions by Insulin Tolerance Test and Sodium Depletion in Women With Nonclassical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Comparison With Healthy Volunteers.
The risk of adrenal insufficiency in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is not well documented. Indication of cortisol replacement therapy in situation of acute stress or at long term is thus controversial. The mineralocorticoid reserve of these patients has never been evaluated.
Hypothesis: The glucocorticoid and mineralocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency is comparable with the adrenal functions of healthy age- sexe- and BMI-matched subjects.
Read the detailed description
The primary end-point of the study is to evaluate the glucocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency (= patients) by comparing the maximal cortisol concentrations obtained during insulin tolerance test (ITT) in the patients and in the healthy volunteers.
The secondary end-point of the study is to determine the % of patients with a maximal plasma cortisol concentration greater or equal to 18μg/dL during ITT; compare the maximal plasma ACTH and salivary cortisol concentration during ITT in the two study groups; to evaluate the mineralocorticoid function of the patients by comparing the variations (changes from baseline) of the plasma renin, aldosterone, urinary aldosterone, systolic and diastolic blood pressure and pulse wave velocity in response to sodium depletion in the patients and in the healthy volunteers.
Women with nonclassical 21-hydroxylase deficiency followed in the Endocrinology and reproduction illnesses Service of the BICETRE Hospital, LE KREMLIN-BICETRE, France and female healthy volunteers will be proposed to participate.
Before inclusion patients must be genotyped and both patients and healthy volunteers must undergo an ACTH (Synacthen 250 μg IV) test for plasma cortisol and 17-hydroxyprogesterone concentration assessments.
After inclusion:
- ITT: IV injection of 0.10-0.2U/kg of insulin (ACTRAPID) at 09h00, dose adapted to BMI, with repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin injection for assessment of the glucocorticoid function, at the One Day Hospital of the Endocrinology and reproduction illnesses Service of the BICETRE Hospital, LE KREMLIN BICETRE.
- Sodium depletion test: obtained by PO administration of 40 mg of furosemide (LASILIX) at 09h00 in combination with low sodium diet (20mmol of Na/day) with repeated measures for assessment of the mineralocorticoid function during 24 hours after the drug administration at the Clinical Investigation Center of The George POMPIDOU Hospital, Paris.
- Being tested
- Functional explorations
- Keywords
- Adrenocortical function, Adrenal hyperplasia, Congenital, 21-hydroxylase, deficiency, cortisol, replacement therapy, Woman, Healthy people
- Medical subject headings
- Adrenal Hyperplasia, Congenital, Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional explorationsOther
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
Functional explorationsOther
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
| Study group | Role | What they receive |
|---|---|---|
| Cases | Experimental | Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in female patients with non classical 21-hydroxylase deficiency. Receives: Other: Functional explorations |
| Control | Experimental | Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls. Receives: Other: Functional explorations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal plasma cortisol concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Measured: Before and up to two hours after Insulin injection (Insulin tolerance test)
Secondary outcomes (6)
% of patients with maximal plasma cortisol concentration >=18microg/dl
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Measured: Before and up to two hours after Insulin injection (Insulin tolerance test)
Maximal plasma ACTH concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Measured: Before and up to two hours after Insulin injection (Insulin tolerance test)
Maximal salivary cortisol concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Measured: Before and up to two hours after Insulin injection (Insulin tolerance test)
Variation (change from baseline) of plasma rennin and plasma aldosterone concentration
Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration
Measured: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Variation (change from baseline) of urinary aldosterone concentration
Repeated measures in 4-hour urine portions after oral furosemide administration
Measured: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Variation (change from baseline) of the systolic, diastolic blood pressure and pulse wave velocity
Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration
Measured: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2015
- Study completionNov 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal Hyperplasia, CongenitalStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Kamenicky, MD, PhD, Principal investigator, Assistance Publique Hôpitaux de Paris - Bicêtre Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01862380
- Sponsor's protocol ID
- P111005
- Acronym
- EVAF-21
- Status last verified
- Sep 2016
- First submitted
- 22 May 2013
- Last updated
- 29 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Kamenicky P, Blanchard A, Lamaziere A, Piedvache C, Donadille B, Duranteau L, Bry H, Gautier JF, Salenave S, Raffin-Sanson ML, Genc S, Pietri L, Christin-Maitre S, Thomas J, Lorthioir A, Azizi M, Chanson P, Le Bouc Y, Brailly-Tabard S, Young J. Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz005. doi: 10.1210/clinem/dgz005.
PubMed 31529070
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Adrenocortical Functions by Insulin Tolerance Test and Sodium Depletion in Women With Nonclassical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Comparison With Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT01862380
- Acronym / sponsor ID
- EVAF-21 / P111005
- Keywords
- Adrenocortical function, Adrenal hyperplasia, Congenital, 21-hydroxylase, deficiency, cortisol, replacement therapy, Woman, Healthy people
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Nov 2016 (estimated)
- First posted
- 24 May 2013 (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.
The risk of adrenal insufficiency in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is not well documented. Indication of cortisol replacement therapy in situation of acute stress or at long term is thus controversial. The mineralocorticoid reserve of these patients has never been evaluated.
Hypothesis: The glucocorticoid and mineralocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency is comparable with the adrenal functions of healthy age- sexe- and BMI-matched subjects.
Detailed description
The primary end-point of the study is to evaluate the glucocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency (= patients) by comparing the maximal cortisol concentrations obtained during insulin tolerance test (ITT) in the patients and in the healthy volunteers.
The secondary end-point of the study is to determine the % of patients with a maximal plasma cortisol concentration greater or equal to 18μg/dL during ITT; compare the maximal plasma ACTH and salivary cortisol concentration during ITT in the two study groups; to evaluate the mineralocorticoid function of the patients by comparing the variations (changes from baseline) of the plasma renin, aldosterone, urinary aldosterone, systolic and diastolic blood pressure and pulse wave velocity in response to sodium depletion in the patients and in the healthy volunteers.
Women with nonclassical 21-hydroxylase deficiency followed in the Endocrinology and reproduction illnesses Service of the BICETRE Hospital, LE KREMLIN-BICETRE, France and female healthy volunteers will be proposed to participate.
Before inclusion patients must be genotyped and both patients and healthy volunteers must undergo an ACTH (Synacthen 250 μg IV) test for plasma cortisol and 17-hydroxyprogesterone concentration assessments.
After inclusion:
- ITT: IV injection of 0.10-0.2U/kg of insulin (ACTRAPID) at 09h00, dose adapted to BMI, with repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin injection for assessment of the glucocorticoid function, at the One Day Hospital of the Endocrinology and reproduction illnesses Service of the BICETRE Hospital, LE KREMLIN BICETRE.
- Sodium depletion test: obtained by PO administration of 40 mg of furosemide (LASILIX) at 09h00 in combination with low sodium diet (20mmol of Na/day) with repeated measures for assessment of the mineralocorticoid function during 24 hours after the drug administration at the Clinical Investigation Center of The George POMPIDOU Hospital, Paris.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | Experimental | Other: Functional explorationsFunctional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in female patients with non classical 21-hydroxylase deficiency. |
| Control | Experimental | Other: Functional explorationsFunctional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- women aged 18-50 years with nonclassical 21-hydroxylase deficiency with homozygous or compound heterozygous mutations of CYP21A2 and plasma 17-hydroxyprogesterone concentration after stimulation with synacthen >= 10ng/mL
- age matched female healthy volunteers with plasma 17-hydroxyprogesterone concentration after stimulation with synacthen < 2ng/mL
Key exclusion criteria (6 listed)
- treatment with oral or local glucocorticoids < 1 year
- oral estroprogestative contraception < 3 months
- spironolactone < 3 months
- cyproterone acetate < 3 months
- treatment modifying the activity of the renin - angiotensine - aldosterone system < 2 weeks
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 |
|---|---|---|
| Functional explorationsFunctional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively | Other | Cases |
| Functional explorationsFunctional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively | Other | Control |
Primary outcome
Maximal plasma cortisol concentration
Time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
6 secondary outcomes
% of patients with maximal plasma cortisol concentration >=18microg/dl
Time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)
Maximal plasma ACTH concentration
Time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)
Maximal salivary cortisol concentration
Time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)
Variation (change from baseline) of plasma rennin and plasma aldosterone concentration
Time frame: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Variation (change from baseline) of urinary aldosterone concentration
Time frame: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Variation (change from baseline) of the systolic, diastolic blood pressure and pulse wave velocity
Time frame: Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Derived from this study: PubMed 31529070Kamenicky P, Blanchard A, Lamaziere A, Piedvache C, Donadille B, Duranteau L, Bry H, Gautier JF, Salenave S, Raffin-Sanson ML, Genc S, Pietri L, Christin-Maitre S, Thomas J, Lorthioir A, Azizi M, Chanson P, Le Bouc Y, Brailly-Tabard S, Young J. Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz005. doi: 10.1210/clinem/dgz005.
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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.
Peter Kamenicky, MD, PhD principal investigator
Assistance Publique Hôpitaux de Paris - Bicêtre Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Functional explorations in people with Adrenal Hyperplasia, Congenital and 21-hydroxylase Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 inclusion and 6 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 29 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 1 site in France. 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?
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?
Maximal plasma cortisol concentration (time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)). 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 NCT01862380, which also lists 1 linked publication.
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 29 Sep 2016.