Working… Menu

Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00519818
Recruitment Status : Completed
First Posted : August 23, 2007
Results First Posted : August 27, 2014
Last Update Posted : March 24, 2016
National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
Diurnal Limited

Brief 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.

Condition or disease Intervention/treatment Phase
Congenital Adrenal Hyperplasia 21-Hydroxylase Deficiency Adrenogenital Syndrome Drug: Chronocort Drug: Cortef Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open Label, Crossover Pharmacokinetic and Pharmacodynamic Study to Compare Chronocort Versus Cortef in Patients With CAH
Study Start Date : August 2007
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Arm Intervention/treatment
Experimental: Cortef and Chronocort
Cortef 3 times daily(total dose 30 mg)for minimum of 7 days followed by Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration
Drug: Chronocort
Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration
Other Name: Hydrocortisone modified release tablet treatment

Drug: Cortef
Cortef 3 times daily(total dose 30 mg)for minimum of 7 days
Other Name: Hydrocortisone immediate release tablet

Primary Outcome Measures :
  1. Chronocort vs. Cortef Cortisol Concentrations (AUC Over 24 Hours - Time Points 0,.5,1,1.5,2,3,4,5,6,7,8,10,10.5,11, 11.5,12,13,15,17,17.5,18,18.5,19,20,22,24 Post Dose). [ Time Frame: Cortef after one week, Chronocort after one month ]

Secondary Outcome Measures :
  1. 17 Hydroxyprogesterone at 08.00 Hours [ Time Frame: Cortef after one week compared with Chronocort after one month ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Satisfactory pre-trial screening

Provision of signed written informed consent and written assent from patients less than 18 years old, as applicable.

Good general health.

Females of childbearing potential must have a negative pregnancy test initially and at all visits. Females who are engaging in sexual intercourse must be using medically acceptable method of contraception.


Co-morbid condition requiring daily administration of a medication that induces hepatic enzymes or interferes with the metabolism of glucocorticoids.

Clinical or biochemical evidence of hepatic or renal disease. Creatinine above the normal range or elevated liver function tests (Transaminases greater than 1.5 the upper limits of normal).

Females who are pregnant or lactating.

Patients with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the trial.

Participation in another clinical trial of an investigational or licensed drug or device within 3 months prior to inclusion in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00519818

Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Diurnal Limited
National Institutes of Health Clinical Center (CC)
Layout table for investigator information
Principal Investigator: Deborah Merck, MD National Institutes of Health (NIH)

Layout table for additonal information
Responsible Party: Diurnal Limited Identifier: NCT00519818     History of Changes
Other Study ID Numbers: 070211
First Posted: August 23, 2007    Key Record Dates
Results First Posted: August 27, 2014
Last Update Posted: March 24, 2016
Last Verified: February 2016
Keywords provided by Diurnal Limited:
Congenital Adrenal Hyperplasia
Additional relevant MeSH terms:
Layout table for MeSH terms
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Pathologic Processes
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
Anti-Inflammatory Agents