Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia

Sponsor

University of Minnesota (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03718234

Collaborator

(none)

Enrollment

Location

Arms

53.9

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Subcutaneous hydrocortisone Drug: Standard glucocorticoid therapy	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a non-randomized crossover study design.This is a non-randomized crossover study design.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subcutaneous Hydrocortisone via Infusion Pump 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 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. Other Names: Hydrocortisone delivered via subcutaneous pump
Active Comparator: Standard glucocorticoid therapy Subjects in this arm will continue on standard oral hydrocortisone therapy	Drug: Standard glucocorticoid therapy Subjects in this arm will continue on standard oral hydrocortisone therapy

Arm

Intervention/Treatment

Experimental: Subcutaneous Hydrocortisone via Infusion Pump

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

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.

Other Names:

Hydrocortisone delivered via subcutaneous pump

Active Comparator: Standard glucocorticoid therapy

Subjects in this arm will continue on standard oral hydrocortisone therapy

Drug: Standard glucocorticoid therapy

Subjects in this arm will continue on standard oral hydrocortisone therapy

Outcome Measures

Primary Outcome Measures

Duration of hypocortisolemia and hypercortisolemia will be significantly shorter [From date of randomization assessed up to 20 weeks.]
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)
Serum concentrations will be within an acceptable range [From date of randomization assessed up to 20 weeks.]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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