Dexamethasone Treatment of Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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The purpose of this study is to determine if dexamethasone given at night is a more effective treatment for congenital adrenal hyperplasia in young children than standard three times per day hydrocortisone. Our hypothesis is that nocturnal dexamethasone will lead to more efficient suppression of the hypothalamic-pituitary-adrenal axis. We performed a cross-over trial comparing hormonal control during two 24-hour hospitalizations, one on hydrocortisone and one on nocturnal dexamethasone.

Detailed Description
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This is a Phase II clinical trial, intended to estimate the effect of instituting Dexamethasone therapy in comparison to prior standard therapy. Each subject provides his own baseline data. There is no control group. Patients with CAH who meet inclusion criteria will be admitted to the clinical research center for two 24 hour hospitalizations. Adrenal hormone profiles will be measured during each hospitalization. The patient will take his or her baseline hydrocortisone regimen during one hospitalization and a new regimen consisting of a single daily nocturnal dose of Dexamethasone during the second hospitalization.

Official Title
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Dexamethasone Treatment of Congenital Adrenal Hyperplasia

Conditions
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Adrenal Hyperplasia, Congenital

Intervention / Treatment
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* Drug: dexamethasone
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Classic salt-wasting 21-hydroxylase deficient congenital adrenal hyperplasia Pre-pubertal children with bone ages below 8 years Exclusion Criteria: Age less than 2 years Patients with additional medical conditions necessitating glucocorticoid therapy. Patients on phenytoin, barbiturates, and rifampin as these medications accelerate the metabolism of glucocorticoids. Patients on ketoconazole as this medication increases the bioavailability of glucocorticoids.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Experimental therapy with nocturnal dexamethasone. | Drug: dexamethasone<br>* Dexamethasone will be given at a dose that equals 1/50 of the total daily hydrocortisone dose of the patient. It will be given in solution form at 10 PM for 3 days.<br>* Other names: Decadron;Drug: Hydrocortisone<br>* Subjects were given their baseline hydrocortisone regimen which was three times daily for 4 of the subjects and twice daily for one subject. Doses were given at 8 AM, 2 PM, and 8 PM. The 2 PM time point was skipped for the subject who received hydrocortisone twice daily. Doses ranged from 6.9 to 18.5 milligrams per meter squared per day and were based on each individual's baseline regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Difference in the Mean Log Transformed Area Under the Curve of 17-hydroxyprogesterone Between Regimens | Each subject was admitted for 2 24 hour hospitalizations, one on hydrocortisone and one on dexamethasone. Due to the timing of blood draws, the serum hormonal profile was only measured for 23 hours. The primary outcome was the Percent Difference in the Mean log transformed Area under the curve of 17-hydroxyprogesterone between the two regimens. | 23 hours |