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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01862380
First received: May 22, 2013
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Adrenal Hyperplasia, Congenital
21-hydroxylase Deficiency
Other: Functional explorations

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Maximal plasma cortisol concentration [ Time Frame: Before and up to two hours after Insulin injection (Insulin tolerance test) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Before and up to two hours after Insulin injection (Insulin tolerance test) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Repeated measures 1, 2, 3, 6, 9, 12, 24 hours after oral furosemide administration


Estimated Enrollment: 40
Study Start Date: February 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cases
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in female patients with non classical 21-hydroxylase deficiency.
Other: Functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively
Experimental: Control
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively in healthy female controls.
Other: Functional explorations
Functional explorations of cortisol and aldosterone production during stimulation by ITT and sodium depletion respectively

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.
  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • women aged 18-40 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 and BMI-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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01862380

Contacts
Contact: Peter Kamenicky, MD, PhD + 33(1)45 21 37 06 peter.kamenicky@bct.aphp.fr

Locations
France
Assistance Publique - Hôpitaux de Paris, Bicêtre Hospital Recruiting
Le Kremlin-bicetre, France, 94 275
Contact: Peter Kamenicky, MD, PhD    + 33(1)45 21 37 06    peter.kamenicky@bct.aphp.fr   
Principal Investigator: Peter Kamenicky, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Peter Kamenicky, MD, PhD Assistance Publique Hôpitaux de Paris - Bicêtre Hospital
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01862380     History of Changes
Other Study ID Numbers: P111005
Study First Received: May 22, 2013
Last Updated: July 3, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Adrenocortical function
Adrenal hyperplasia, Congenital
21-hydroxylase
deficiency
cortisol
replacement therapy
Woman
Healthy people

Additional relevant MeSH terms:
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Hyperplasia
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders
Pathologic Processes
Hydrocortisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014