Clinical Trial: Adrenocortical Functions in Women With Nonclassical 21-hydroxylase Deficiency.

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Evaluation of Adrenocortical Functions by Insulin Tolerance Test and Sodium Depletion in Women With Nonclassical Congenital Adrenal Hyperplasia Due to 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 Summary:

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 BI
    Sponsor: Assistance Publique - Hôpitaux de Paris

    Current 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


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • % of patients with maximal plasma cortisol concentration >=18microg/dl [ 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
    • Maximal plasma ACTH 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
    • Maximal salivary 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
    • 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) ]
      Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration
    • Variation (change from baseline) of urinary aldosterone concentration [ Time Frame: Before and up to 24 hours after oral furosemide administration (Sodium depletion test) ]
      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 [ Time Frame: Before and up to 24 hours after oral furosemide administration (Sodium depletion test) ]
      Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: May 22, 2013
    Date Started: February 2013
    Date Completion: November 2016
    Last Updated: September 28, 2016
    Last Verified: September 2016