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COrticosteroid in Congenital Adrenal Hyperplasia

Phase 2
Conditions
Congenital Adrenal Hyperplasia
Interventions
Biological: Hormonal balance measurements
Biological: metabolic balance measurements
Biological: bone balance measurements
Behavioral: quality of life assessment
Registration Number
NCT02552251
Lead Sponsor
University Hospital, Caen
Brief Summary

Congenital adrenal hyperplasia (CAH) results from a deficiency of a key enzyme in the biosynthesis of cortisol, mainly 21-hydroxylase, resulting in its classic form a neonatal salt loss syndrome and / or a virilization syndrome in girls. The treatment of the disorder in adulthood involves administering steroidal compounds with the aim to substitute the gluco- and mineralocorticoid deficit on the one hand, and effectively curb the adrenal hyperplasia and adrenal androgen pathway in girls . The terms of glucocorticoid treatment are not clearly codified and are based on several steroidal compounds and various protocols. The advantages in terms of adrenal suppression and disadvantages - including bone and metabolic - different treatments have not been clearly established in the literature. The main objective of this study is to compare among adults with HCS in its classical form the impact on hormonal parameters adrenal suppression glucocorticoid of 3 types of treatment administered to equivalent dose and according to the usual procedures. The secondary objective is to compare in the same patients the impact of different drugs and treatments on several metabolic bone parameters. The study will include 40 adult patients bearing a HCS in its classical form and will include 3 treatment sequences of eight weeks each, during which they will be administered sequentially in random order at random and according to the known equivalences hydrocortisone, prednisone (CORTANCYL) and dexamethasone (DECTANCYL).

Randomization will be stratified based on previous DMARDs in the investigation that may be different for different patients, knowing that France hydrocortisone and dexamethasone are used mainly for the treatment of congenital adrenal hyperplasia. The judging criteria will be: i) the criteria of adrenal hormone suppression: plasma levels of testosterone, androstenedione, 17 OHP, ACTH and diurnal variations of the 17 OH progesterone salivary ii) the criteria of the metabolic impact of glucocorticoids: plasma glucose levels , blood lipids, and insulin sensitivity index HOMA-R calculated from glucose and insulin, iii) the criteria of bone impact of glucocorticoids: plasma for CTX bone resorption and bone alkaline phosphatase P1NP for bone formation iv) the living quality criteria evaluated by the PGWB Questionnaire (Psychological General Well-Being). The duration of the study period will be 24 months.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
40
Inclusion Criteria
  • Pubescent women over 18 in genital activity (premenopausal)
  • Suffering from congenital adrenal hyperplasia in its classical form with salt loss or pure virilizing
  • Patients who have presented signs of congenital adrenal hyperplasia in its classical form (salt wasting syndrome and / or neonatal masculinization) with elevation of 17 OH progesterone with diagnosis of enzyme block 21 hydroxylase.
  • Patients currently treated by: 1 or 2 Oral compound glucocorticoid as replacement and suppressive therapy + 1 mineralocorticoid if necessary with effective control of substitution + possibly by estrogen-progestin pill.
Exclusion Criteria
  • Liver disease, kidney, bone, diabetes, severe dyslipidemia, pregnancy
  • Postmenopausal women, age over 55 years
  • Concomitant therapy: glucocorticoids supra-physiological doses for other indications, bisphosphonates, vitamin D, oral antidiabetic agents or insulin, lipid lowering agents (eg inflammatory disease, asthma, systemic disease ... ..).
  • participation of the subject to another biomedical research protocol for this study
  • Inability to submit to medical monitoring study for geographical, social or psychological.
  • Severe calorie diet planned or carried out during the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
B :dexamethasone (DECTANCYL)bone balance measurementsdexamethasone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
A: hydrocortisonemetabolic balance measurementshydrocortisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
A: hydrocortisonequality of life assessmenthydrocortisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
B :dexamethasone (DECTANCYL)metabolic balance measurementsdexamethasone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
A: hydrocortisonebone balance measurementshydrocortisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
C : prednisone (CORTANCYL)bone balance measurementsprednisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
A: hydrocortisoneHormonal balance measurementshydrocortisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
C : prednisone (CORTANCYL)quality of life assessmentprednisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
B :dexamethasone (DECTANCYL)Hormonal balance measurementsdexamethasone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
C : prednisone (CORTANCYL)metabolic balance measurementsprednisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
B :dexamethasone (DECTANCYL)quality of life assessmentdexamethasone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
C : prednisone (CORTANCYL)Hormonal balance measurementsprednisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks
Primary Outcome Measures
NameTimeMethod
hormonal parameterschange over baseline, week 8, week 16, week 24

6 points salivary 17 OHP cycle, and 8 am plasma ACTH,testosterone and androstenedione

Secondary Outcome Measures
NameTimeMethod
Quality of Lifechange over baseline, week 8, week 16, week 24

Psychological General Well-Being questionnaire

parameters of bone turnover:change over baseline, week 8, week 16, week 24

CTX and bone alkaline phosphatase P1NP

metabolic parameters:change over baseline, week 8, week 16, week 24

blood glucose and insulin, cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol

Trial Locations

Locations (1)

Service Endocrinologie et Maladies Métaboliques

🇫🇷

Caen, France

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