Overview

This trial is active, not recruiting.

Conditions adrenal hyperplasia, congenital, 21-hydroxylase deficiency
Treatments functional explorations
Sponsor Assistance Publique - Hôpitaux de Paris
Start date February 2013
End date December 2015
Trial size 41 participants
Trial identifier NCT01862380, P111005

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Masking open label
Primary purpose diagnostic
Arm
(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.
functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
(Experimental)
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls.
functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively

Primary Outcomes

Measure
Maximal plasma cortisol concentration
time frame: Before and up to two hours after Insulin injection (Insulin tolerance test)

Secondary Outcomes

Measure
% 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)

Eligibility Criteria

Female participants from 18 years up to 50 years old.

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

Additional Information

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.
Principal investigator Peter Kamenicky, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.