Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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This is an open-label, non-randomized crossover design feasibility trial comparing oral hydrocortisone treatment with interval bolus delivery (pulsatile) of subcutaneous hydrocortisone via infusion pump in children with congenital adrenal hyperplasia. Eight children, ages 4-18 yrs, will have 24-hr pharmacokinetic and pharmacodynamic profiles of cortisol, 17-hydroxyprogesterone and androstenedione concentrations while on oral hydrocortisone therapy (admission 1), during an initial trial of the subcutaneous hydrocortisone pump (admission 2), and after 6 weeks of subcutaneous hydrocortisone pump treatment (admission 3). An integrated pharmacokinetic and pharmacodynamic model will be used to determine cortisol, 17-hydroxyprogesterone and androstenedione parameters to compare the duration of time subjects have these concentrations outside acceptable ranges. Funding Source - FDA OOPD

Official Title
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Interval Bolus Delivery of Subcutaneous Hydrocortisone Via Infusion Pump in Children With Congenital Adrenal Hyperplasia

Conditions
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Congenital Adrenal Hyperplasia, Hyperplasia, Adrenal Hyperplasia, Congenital Disorders, Adrenocortical Hyperfunction, Disorders of Sex Development, Urogenital Abnormalities, Genetic Diseases, Inborn, Steroid Metabolic Diseases, Inborn, Adrenal Gland Disease, Hydrocortisone

Intervention / Treatment
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* Drug: Subcutaneous hydrocortisone
* Drug: Standard glucocorticoid therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 4 - 18 years of age. Classic congenital adrenal hyperplasia (CAH) as confirmed by hormonal and molecular testing. Patients who have been on the same HC dosing regimen for 1 month Exclusion Criteria: Patients with non-classic CAH. Patients on: Dexamethasone Prednisone, or inhaled steroids. Patients with body surface areas under 1m2 or over 2m2 Non-English speaking patients

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 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: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This is a non-randomized crossover study design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subcutaneous Hydrocortisone via Infusion Pump<br>Patients will receive a subcutaneous injection of hydrocortisone (HC). Each patient's total daily dose (TDD) of oral tablet hydrocortisone to determine the doses to be delivered of the study drug. The 24-hr schedule and percentage of the TDD of HC will be as follows: approximately 60% of the TDD of HC will be delivered in 3 equal pulses at 0300, 0600 and 0900. Another 35% will be delivered in 3 equal pulses at 1200, 1500 and 1800 and the remaining 5% at 2100 and 2400. | Drug: Subcutaneous hydrocortisone<br>* Patients will be monitored and receive an interval bolus SQHC dosing regimen that more closely mimics cortisol, 17OHP and D4A circadian and ultradian rhythms than conventional oral HC dosing.<br>* Other names: Hydrocortisone delivered via subcutaneous pump;|
| Active Comparator: Standard glucocorticoid therapy<br>Subjects in this arm will continue on standard oral hydrocortisone therapy | Drug: Standard glucocorticoid therapy<br>* Subjects in this arm will continue on standard oral hydrocortisone therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hypocortisolemia and hypercortisolemia will be significantly shorter | Duration of hypocortisolemia and hypercortisolemia will be significantly shorter on the interval bolus delivery (pulsatile) of subcutaneous hydrocortisone (admissions 2 and 3) than with conventional oral hydrocortisone dosing (admission 1) | From date of randomization assessed up to 20 weeks. | 
| Serum concentrations will be within an acceptable range | Duration of time 17-hydroxyprogesterone and androstenedione serum concentrations are outside an acceptable range of suppression will be significantly shorter while on on the interval bolus delivery (pulsatile) of subcutaneous hydrocortisone (admissions 2 and 3) than with oral hydrocortisone dosing (admission 1) | From date of randomization assessed up to 20 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adrenal gland diseases, cortisol succinate, hydrocortisone, hyperplasia