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

NCT00519818 | Completed Phase 1 Results

• 1 other identifier: 070211
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Adrenal Hyperplasia; 21-Hydroxylase Deficiency; Adrenogenital Syndrome

Keywords

Congenital Adrenal Hyperplasia; Hydrocortisone; Pharmacokinetic; Pharmacodynamic

Outcome Measures

Primary Outcomes (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).

  Cortef after one week, Chronocort after one month

Secondary Outcomes (1)

• 17 Hydroxyprogesterone at 08.00 Hours

  Cortef after one week compared with Chronocort after one month

Study Arms (1)

Cortef and Chronocort

EXPERIMENTAL

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; Drug: Cortef

Interventions

Chronocort DRUG

Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration

Also known as: Hydrocortisone modified release tablet treatment

Cortef and Chronocort

Cortef DRUG

Cortef 3 times daily(total dose 30 mg)for minimum of 7 days

Also known as: Hydrocortisone immediate release tablet

Cortef and Chronocort

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• National Institutes of Health Clinical Center (CC): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001 Mar;30(1):15-30. doi: 10.1016/s0889-8529(08)70017-3.

  PMID: 11344933 BACKGROUND

• Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005 Jun 18-24;365(9477):2125-36. doi: 10.1016/S0140-6736(05)66736-0.

  PMID: 15964450 BACKGROUND

• Krieger DT, Allen W, Rizzo F, Krieger HP. Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab. 1971 Feb;32(2):266-84. doi: 10.1210/jcem-32-2-266. No abstract available.

  PMID: 4321505 BACKGROUND

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital; Congenital adrenal hyperplasia due to 21 hydroxylase deficiency; Adrenogenital Syndrome

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Richard JM Ross
• Organization: Diurnal Ltd

r.j.ross@sheffield.ac.uk

0044 114 2712386

Study Officials

• Deborah Merck, MD

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2007
• First Posted: August 23, 2007
• Study Start: August 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: April 26, 2022
• Results First Posted: August 27, 2014

Record last verified: 2022-04

Locations

US (1)