COrticosteroid in Congenital Adrenal Hyperplasia (COCA)

Comparative Study of the Use of Glucocorticoids in the Treatment of Congenital Adrenal Hyperplasia in Its Classical Form

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.

Study Overview

• Status: Unknown
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Biological: Hormonal balance measurements; Biological: metabolic balance measurements; Biological: bone balance measurements; Behavioral: quality of life assessment

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Caen, France, 14000
    • Recruiting
    • Service Endocrinologie et Maladies Métaboliques
    • Contact: Yves REZNIK, MD, PhD; Phone Number: 02.31.06.45.86; Email: reznik-y@chu-caen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A: hydrocortisone; hydrocortisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks	Biological: Hormonal balance measurements; Biological: metabolic balance measurements; Biological: bone balance measurements; Behavioral: quality of life assessment
EXPERIMENTAL: B :dexamethasone (DECTANCYL); dexamethasone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks	Biological: Hormonal balance measurements; Biological: metabolic balance measurements; Biological: bone balance measurements; Behavioral: quality of life assessment
EXPERIMENTAL: C : prednisone (CORTANCYL); prednisone equivalent to physiological doses for each patient Strategy: administration of glucocorticoids during sequences of eight weeks	Biological: Hormonal balance measurements; Biological: metabolic balance measurements; Biological: bone balance measurements; Behavioral: quality of life assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hormonal parameters	6 points salivary 17 OHP cycle, and 8 am plasma ACTH,testosterone and androstenedione	change over baseline, week 8, week 16, week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
parameters of bone turnover:	CTX and bone alkaline phosphatase P1NP	change over baseline, week 8, week 16, week 24
metabolic parameters:	blood glucose and insulin, cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol	change over baseline, week 8, week 16, week 24
Quality of Life	Psychological General Well-Being questionnaire	change over baseline, week 8, week 16, week 24

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2015

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: September 15, 2015
• First Posted (ESTIMATE): September 17, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): September 17, 2015
• Last Update Submitted That Met QC Criteria: September 15, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction
• Other Study ID Numbers: 11-059