search
Back to results

Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency. (EVAF-21)

Primary Purpose

Adrenal Hyperplasia, Congenital, 21-hydroxylase Deficiency

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Functional explorations
Functional explorations
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Adrenal Hyperplasia, Congenital focused on measuring Adrenocortical function, Adrenal hyperplasia, Congenital, 21-hydroxylase, deficiency, cortisol, replacement therapy, Woman, Healthy people

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Sites / Locations

  • Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cases

Control

Arm Description

Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in female patients with non classical 21-hydroxylase deficiency.

Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls.

Outcomes

Primary Outcome Measures

Maximal plasma cortisol concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection

Secondary Outcome Measures

% of patients with maximal plasma cortisol concentration >=18microg/dl
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Maximal plasma ACTH concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Maximal salivary cortisol concentration
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
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
Variation (change from baseline) of urinary aldosterone concentration
Repeated measures in 4-hour urine portions after oral furosemide administration
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

Full Information

First Posted
May 22, 2013
Last Updated
September 28, 2016
Sponsor
Assistance Publique - Hôpitaux de Paris
search

1. Study Identification

Unique Protocol Identification Number
NCT01862380
Brief Title
Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency.
Acronym
EVAF-21
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Unknown status
Study Start Date
February 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
November 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Hyperplasia, Congenital, 21-hydroxylase Deficiency
Keywords
Adrenocortical function, Adrenal hyperplasia, Congenital, 21-hydroxylase, deficiency, cortisol, replacement therapy, Woman, Healthy people

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cases
Arm Type
Experimental
Arm Description
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in female patients with non classical 21-hydroxylase deficiency.
Arm Title
Control
Arm Type
Experimental
Arm Description
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls.
Intervention Type
Other
Intervention Name(s)
Functional explorations
Intervention Description
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
Intervention Type
Other
Intervention Name(s)
Functional explorations
Intervention Description
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
Primary Outcome Measure Information:
Title
Maximal plasma cortisol concentration
Description
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Time Frame
Before and up to two hours after Insulin injection (Insulin tolerance test)
Secondary Outcome Measure Information:
Title
% of patients with maximal plasma cortisol concentration >=18microg/dl
Description
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Time Frame
Before and up to two hours after Insulin injection (Insulin tolerance test)
Title
Maximal plasma ACTH concentration
Description
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Time Frame
Before and up to two hours after Insulin injection (Insulin tolerance test)
Title
Maximal salivary cortisol concentration
Description
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
Time Frame
Before and up to two hours after Insulin injection (Insulin tolerance test)
Title
Variation (change from baseline) of plasma rennin and plasma aldosterone concentration
Description
Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration
Time Frame
Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Title
Variation (change from baseline) of urinary aldosterone concentration
Description
Repeated measures in 4-hour urine portions after oral furosemide administration
Time Frame
Before and up to 24 hours after oral furosemide administration (Sodium depletion test)
Title
Variation (change from baseline) of the systolic, diastolic blood pressure and pulse wave velocity
Description
Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration
Time Frame
Before and up to 24 hours after oral furosemide administration (Sodium depletion test)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Kamenicky, MD, PhD
Organizational Affiliation
Assistance Publique Hôpitaux de Paris - Bicêtre Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital
City
Le Kremlin-bicetre
ZIP/Postal Code
94 275
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
31529070
Citation
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.
Results Reference
derived

Learn more about this trial

Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency.

We'll reach out to this number within 24 hrs