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

Primary Purpose

Congenital Adrenal Hyperplasia, 21-Hydroxylase Deficiency, Adrenogenital Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Chronocort
Cortef
Sponsored by
Diurnal Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Adrenal Hyperplasia focused on measuring Congenital Adrenal Hyperplasia, Hydrocortisone, Pharmacokinetic, Pharmacodynamic

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cortef and Chronocort

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

17 Hydroxyprogesterone at 08.00 Hours

Full Information

First Posted
August 22, 2007
Last Updated
April 5, 2022
Sponsor
Diurnal Limited
Collaborators
National Institutes of Health Clinical Center (CC)
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1. Study Identification

Unique Protocol Identification Number
NCT00519818
Brief Title
Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia
Official Title
A Phase 2, Open Label, Crossover Pharmacokinetic and Pharmacodynamic Study to Compare Chronocort Versus Cortef in Patients With CAH
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Diurnal Limited
Collaborators
National Institutes of Health Clinical Center (CC)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Adrenal Hyperplasia, 21-Hydroxylase Deficiency, Adrenogenital Syndrome
Keywords
Congenital Adrenal Hyperplasia, Hydrocortisone, Pharmacokinetic, Pharmacodynamic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cortef and Chronocort
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Chronocort
Other Intervention Name(s)
Hydrocortisone modified release tablet treatment
Intervention Description
Chronocort 30 mg once daily nigh time dose for 28 +/- 3 days duration
Intervention Type
Drug
Intervention Name(s)
Cortef
Other Intervention Name(s)
Hydrocortisone immediate release tablet
Intervention Description
Cortef 3 times daily(total dose 30 mg)for minimum of 7 days
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
17 Hydroxyprogesterone at 08.00 Hours
Time Frame
Cortef after one week compared with Chronocort after one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: 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. EXCLUSION CRITERIA: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah Merck, MD
Organizational Affiliation
National Institutes of Health (NIH)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11344933
Citation
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.
Results Reference
background
PubMed Identifier
15964450
Citation
Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005 Jun 18-24;365(9477):2125-36. doi: 10.1016/S0140-6736(05)66736-0.
Results Reference
background
PubMed Identifier
4321505
Citation
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.
Results Reference
background

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

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