Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Congenital Adrenal Hyperplasia 21-Hydroxylase Deficiency Adrenogenital Syndrome |
Drug: Chronocort for the treatment of CAH |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: 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 |
- Chronocort vs. Cortef cortisol concentrations (max, min, AUC).
- Changes in adrenal hormone concentrations, changes in fatigue, changes in weight.
| Enrollment: | 20 |
| Study Start Date: | August 2007 |
| Study Completion Date: | May 2009 |
| Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
-
Drug: Chronocort for the treatment of CAH
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.
Eligibility| Ages Eligible for Study: | 16 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
Completed Part 1 of the study.
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.
EXCLUSION CRITERIA:
Co-morbin 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 (ALT or AST 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.
Contacts and Locations More Information
Publications:
| Responsible Party: | Professor Richard Ross, Diurnal Limited |
| ClinicalTrials.gov Identifier: | NCT00519818 History of Changes |
| Other Study ID Numbers: | 070211, 07-CH-0211 |
| Study First Received: | August 22, 2007 |
| Last Updated: | October 6, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Diurnal Limited:
|
Congenital Adrenal Hyperplasia Hydrocortisone Pharmacokinetic Pharmacodynamic CAH |
Additional relevant MeSH terms:
|
Adrenogenital Syndrome Adrenal Hyperplasia, Congenital Adrenocortical Hyperfunction Hyperplasia Disorders of Sex Development Urogenital Abnormalities Congenital Abnormalities Gonadal Disorders Endocrine System Diseases Genetic Diseases, Inborn Steroid Metabolism, Inborn Errors Metabolism, Inborn Errors |
Metabolic Diseases Adrenal Gland Diseases Pathologic Processes Cortisol succinate Hydrocortisone acetate Hydrocortisone 17-butyrate 21-propionate Hydrocortisone Hydrocortisone-17-butyrate Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Dermatologic Agents |
ClinicalTrials.gov processed this record on May 22, 2013