Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia
Condition: Congenital Adrenal Hyperplasia; 21-Hydroxylase Deficiency; Adrenogenital Syndrome
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Hyperplasia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will test a new, extended release form of hydrocortisone called Chronocort in
      patients with congenital adrenal hyperplasia (CAH). People with CAH do not make enough of the
      adrenal hormones cortisol and aldosterone, and their adrenal glands make too much of the sex
      hormone androgen. Medicines called glucocorticoids (hydrocortisone, dexamethasone and
      prednisone) are currently used to treat CAH, but finding the best dose of these drugs that
      effectively lowers androgens without causing undesirable side effects, such as weight gain
      and slow growth rate in children, is often difficult to achieve.

      Adolescents and adults with CAH due to 21-hydroxylase deficiency may be eligible for this
      study. Children 16 years of age and older are eligible with confirmation by bone age that
      they are no longer growing.

      Participants undergo the following tests and procedures during two inpatient visits one month
      apart at the NIH Clinical Center:

        -  Medical history and physical examination.

        -  Medications: Following 7 days of Cortef (standard drug treatment for CAH), patients
           begin taking Chronocort on day 3 of hospitalization and continue the tablets once a day
           for 1 month.

        -  Blood tests: A catheter (plastic tube) is inserted in a vein and left in place for
           frequent blood draws in order to avoid repeated needlesticks. Blood is drawn for
           chemistries, blood count, pregnancy test in women, and for serial tests (up to 26
           samples in a 24-hour period) to measure hormone levels.

        -  24-hour urine test.

        -  Height and weight measurements.

      Between the two hospitalizations, patients are contacted by NIH weekly to check for possible
      side effects from Chronocort. Two weeks after the first visit, patients also will have blood
      drawn by their regular doctor or a local clinic. A few days before the second
      hospitalization, patients undergo a 20-minute telephone questionnaire about energy level and
      well being.

      About 30 days after discharge from the second hospitalization, patients are followed up with
      a telephone call to see how they are doing.
    

Detailed description: 
      Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disease of the
      adrenal cortex characterized by cortisol deficiency with or without aldosterone deficiency,
      and androgen excess. The severe or classic form occurs in 1 in 15,000 births worldwide, while
      the mild non-classic form is a common cause of hyperandrogenism. The discovery of
      glucocorticoid therapy as a treatment for CAH occurred in the 1950's resulting in patients
      with classic CAH surviving to live a normal lifespan. However, existing treatment is
      suboptimal and many unresolved clinical problems exist. Standard hormone replacement often
      fails to normalize the growth and development of children with CAH, and adults may experience
      iatrogenic Cushing syndrome, hyperandrogenism, infertility or the development of the
      metabolic syndrome. Chronocort, a newly-developed formulation of hydrocortisone, results in a
      slow release of hydrocortisone that is designed to mimic the normal cortisol circadian
      rhythm. This new medical strategy, physiologic cortisol replacement, offers the prospect of
      an improved outcome of treatment. Chronocort has been safely given to healthy adult males in
      pharmacokinetic studies. This first ever study in patients with CAH is a
      pharmacokinetic/pharmacodynamic study comparing Chronocort to Cortef, the conventional
      immediate-release form of hydrocortisone.
    

Intervention name(s): Chronocort; Cortef
Intervention type(s): Drug; Drug
Intervention description(s): Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration; Cortef 3 times daily(total dose 30 mg)for minimum of 7 days
Other intervention name(s): Hydrocortisone modified release tablet treatment; Hydrocortisone immediate release tablet
Intervention MeSH terms: Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Congenital Adrenal Hyperplasia; Hydrocortisone; Pharmacokinetic; Pharmacodynamic