Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia

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

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

Study Overview

• Status: Completed
• Conditions: Disorders of Sex Development; Urogenital Abnormalities; Congenital Adrenal Hyperplasia; Genetic Diseases, Inborn; Hyperplasia; Adrenocortical Hyperfunction; Congenital Disorders; Hydrocortisone; Adrenal Hyperplasia; Steroid Metabolic Diseases, Inborn; Adrenal Gland Disease
• Intervention / Treatment: Drug: Subcutaneous hydrocortisone

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Prism Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Subcutaneous Hydrocortisone via Infusion Pump; 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

Drug: Subcutaneous hydrocortisone; Pulsatile subcutaneous hydrocortisone administered in 8 doses per day via SQ infusion pump for 6 weeks; Other Names: Hydrocortisone delivered via subcutaneous pump

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol Exposure	24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).	Week 1
Cortisol Exposure	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)	Week 14
17-OHP Exposure	24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).	Week 1
17-OHP Exposure	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)	Week 14
Androstenedione (A4) Exposure	24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).	Week 1
Androstenedione (A4) Exposure	The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)	Week 14

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Kyriaki Sarafoglou, MD, University of Minnesota

Publications and helpful links

General Publications

• Ramirez Alcantara J, Halper A. Adrenal insufficiency updates in children. Curr Opin Endocrinol Diabetes Obes. 2021 Feb 1;28(1):75-81. doi: 10.1097/MED.0000000000000591.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: hydrocortisone; hyperplasia; adrenal gland diseases; cortisol succinate
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Gonadal Disorders; Congenital Abnormalities; Hyperplasia; Genetic Diseases, Inborn; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Metabolic Diseases; Disorders of Sex Development; Urogenital Abnormalities; Steroid Metabolism, Inborn Errors; Adrenal Gland Diseases; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: PEDS-2018-26475; FD-R-6100 (Other Grant/Funding Number: FDA Office of Orphan Products Development)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No