Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia

Phase 1

Completed

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

Brief Summary: This is an open-label, non-randomized, single arm proof-of concept feasibility trial comparing standard oral hydrocortisone (HC) treatment with a six-week intervention of interval bolus delivery (pulsatile) of subcutaneous (SQ) HC via infusion pump in children with congenital adrenal hyperplasia (CAH). Eight children, ages 4-18 yrs, will have 24-hr pharmacokinetic and pharmacodynamic (PKPD) profiles of cortisol, 17- hydroxyprogesterone (17OHP) and androstenedione (A4) concentrations while on standard oral hydrocortisone therapy (admission 1, week 1); during a safety check using a subcutaneous hydrocortisone pump (admission 2, week 7); and after 6 weeks of SQHC pump treatment (admission 3, week 14). A pharmacokinetic and pharmacodynamic analysis will be used to compare cortisol, 17OHP and A4 exposures between standard oral HC therapy (week 1) with SQHC pump treatment (week 14). Funding Source - FDA OOPD

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Subcutaneous Hydrocortisone via Infusion Pump	Subcutaneous hydrocortisone	This is a single arm study. Upon enrollment each participant was admitted for a 24-hr PKPD profile of cortisol, 17OHP and A4 concentrations while on standard oral hydrocortisone therapy (admission 1, week 1). Participant continued on stable oral HC for six weeks. On admission 2, week 7, participant was admitted SQHC pump placement and a safety check was performed to verify absorption of HC was adequate. This consisted of an identical 24-hr PKPD design as used in admission 1. The participants returned to their standard oral HC dosing for 2 weeks while the PKPD profiles from the SQHC pump were being evaluated. The SQHC pump was placed at week 9 and then sent home on the pump. .After 6 weeks of SQHC pump treatment (admission 3, week 14) the participants were admitted and the same 24-hour PKPD design as admissions 1 and 2 profiles was conducted. The subjects were then discharged on their standard oral HC therapy and were followed for an additional 6 weeks

Primary Outcome Measures

Name	Time	Method
Cortisol Exposure	Week 14	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)
17-OHP Exposure	Week 14	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)
Androstenedione (A4) Exposure	Week 14	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)