Adrenal Gland Disease, Adrenal Hyperplasia, Adrenocortical Hyperfunction, Congenital Adrenal Hyperplasia, Congenital Disorders, Disorders of Sex Development, Genetic Diseases, Inborn, Hydrocortisone, Hyperplasia, Steroid Metabolic Diseases, Inborn, Urogenital Abnormalities
Conditions
Keywords
adrenal gland diseases, cortisol succinate, hydrocortisone, hyperplasia
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
Interventions
DRUGSubcutaneous hydrocortisone
Pulsatile subcutaneous hydrocortisone administered in 8 doses per day via SQ infusion pump for 6 weeks
Sponsors
University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a a single arm non-randomized crossover study design.
Eligibility
Sex/Gender
ALL
Age
4 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol Exposure | Week 1 | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). |
| 17-OHP Exposure | Week 1 | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). |
| Androstenedione (A4) Exposure | Week 1 | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Subcutaneous Hydrocortisone Via Infusion Pump |
|---|---|
| Age, Categorical <=18 years | 11 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 9 / 11 | 9 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
17-OHP Exposure
The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)
Time frame: Week 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | 17-OHP Exposure | 26900 hr*ng/dL | Standard Error 16200 |
Primary
17-OHP Exposure
24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).
Time frame: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | 17-OHP Exposure | 46700 hr*ng/dL | Standard Error 19200 |
Primary
Androstenedione (A4) Exposure
The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)
Time frame: Week 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | Androstenedione (A4) Exposure | 1420 hr*ng/dL | Standard Error 968 |
Primary
Androstenedione (A4) Exposure
24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).
Time frame: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | Androstenedione (A4) Exposure | 3350 hr*ng/dL | Standard Error 2410 |
Primary
Cortisol Exposure
24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1).
Time frame: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | Cortisol Exposure | 110 hr*mcg/dL | Standard Error 9.96 |
Primary
Cortisol Exposure
The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3)
Time frame: Week 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Hydrocortisone Via Infusion Pump | Cortisol Exposure | 118 hr*mcg/dL | Standard Error 9.1 |