Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency.

Adrenal Hyperplasia, Congenital Clinical Trial

— 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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01862380
• Other study ID #: P111005
• Status: Active, not recruiting
• Phase: N/A
• First received: May 22, 2013
• Last updated: September 28, 2016
• Start date: February 2013
• Est. completion date: November 2016

Study information

• Verified date: September 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: November 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• 21-hydroxylase Deficiency
• Adrenal Hyperplasia, Congenital
• Adrenocortical Hyperfunction
• Adrenogenital Syndrome
• Hyperplasia

Intervention

Other:
• Functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
• Functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively

Locations

Country	Name	City	State
France	Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital	Le Kremlin-bicetre

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal plasma cortisol concentration	Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection	Before and up to two hours after Insulin injection (Insulin tolerance test)	No
Secondary	% of patients with maximal plasma cortisol concentration >=18microg/dl	Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection	Before and up to two hours after Insulin injection (Insulin tolerance test)	No
Secondary	Maximal plasma ACTH concentration	Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection	Before and up to two hours after Insulin injection (Insulin tolerance test)	No
Secondary	Maximal salivary cortisol concentration	Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection	Before and up to two hours after Insulin injection (Insulin tolerance test)	No
Secondary	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	Before and up to 24 hours after oral furosemide administration (Sodium depletion test)	No
Secondary	Variation (change from baseline) of urinary aldosterone concentration	Repeated measures in 4-hour urine portions after oral furosemide administration	Before and up to 24 hours after oral furosemide administration (Sodium depletion test)	No
Secondary	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	Before and up to 24 hours after oral furosemide administration (Sodium depletion test)	No