Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia

NCT03718234 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: PEDS-2018-26475FD-R-6100
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

adrenal gland diseases; cortisol succinate; hydrocortisone; hyperplasia

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (1)

Subcutaneous Hydrocortisone via Infusion Pump

EXPERIMENTAL

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

Interventions

Subcutaneous hydrocortisone DRUG

Pulsatile subcutaneous hydrocortisone administered in 8 doses per day via SQ infusion pump for 6 weeks

Also known as: Hydrocortisone delivered via subcutaneous pump

Subcutaneous Hydrocortisone via Infusion Pump

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

Prism Clinical Research

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 33278125 DERIVED

MeSH Terms

Conditions

Adrenal Hyperplasia, Congenital; Hyperplasia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Adrenocortical Hyperfunction; Disorders of Sex Development; Urogenital Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Adrenal Gland Diseases

Condition Hierarchy (Ancestors)

Adrenogenital Syndrome; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kyriakie Sarafoglou
• Organization: University of Minnesota

saraf010@umn.edu

6126245965

Study Officials

• Kyriaki Sarafoglou, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a a single arm non-randomized crossover study design.

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 24, 2018
• Study Start: January 1, 2019
• Primary Completion: February 23, 2023
• Study Completion: February 23, 2023
• Last Updated: June 25, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)