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| ID | Type | Description | Link |
|---|---|---|---|
| FD-R-6100 | Other Grant/Funding Number | FDA Office of Orphan Products Development |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Subcutaneous hydrocortisone | Drug | Pulsatile subcutaneous hydrocortisone administered in 8 doses per day via SQ infusion pump for 6 weeks |
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| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Patients with non-classic CAH.
Patients on:
Patients with body surface areas under 1m2 or over 2m2
Non-English speaking patients
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| Name | Affiliation | Role |
|---|---|---|
| Kyriaki Sarafoglou, MD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Prism Clinical Research | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33278125 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 20, 2021 |
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This is a a single arm non-randomized crossover study design.
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cortisol Exposure | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). | Posted | Mean | Standard Error | hr*mcg/dL | Week 1 |
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| Primary | Cortisol Exposure | The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3) | Posted | Mean | Standard Error | hr*mcg/dL | Week 14 |
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| |||||||||||||||||||||||||||
| Primary | 17-OHP Exposure | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). | Posted | Mean | Standard Error | hr*ng/dL | Week 1 |
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| Primary | 17-OHP Exposure | The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3) | Posted | Mean | Standard Error | hr*ng/dL | Week 14 |
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| Primary | Androstenedione (A4) Exposure | 24-hour area under the curve (AUC) following oral hydrocortisone dosing (admission 1). | Posted | Mean | Standard Error | hr*ng/dL | Week 1 |
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| Primary | Androstenedione (A4) Exposure | The 24-hour cortisol area-under-the curve (AUC) while on the interval bolus delivery (pulsatile) of SQHC (admission 3) | Posted | Mean | Standard Error | hr*ng/dL | Week 14 |
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20 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 11 | 0 | 11 | 9 | 11 |
| EG001 | Standard Glucocorticoid Therapy | Subjects in this arm will continue on standard oral hydrocortisone therapy Standard glucocorticoid therapy: Subjects in this arm will continue on standard oral hydrocortisone therapy | 0 | 11 | 0 | 11 | 9 | 11 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stinging/Burning sensation | General disorders | Non-systematic Assessment |
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| Erythema | General disorders | Non-systematic Assessment |
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| Itching | General disorders | Systematic Assessment |
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| Skin rash | General disorders | Systematic Assessment |
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| Excoriation | General disorders | Systematic Assessment |
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| Hives | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Nasal congestion | General disorders | Systematic Assessment |
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| covid | General disorders | Systematic Assessment |
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| Heartburn | General disorders | Systematic Assessment |
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| Ear infection | General disorders | Systematic Assessment |
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| Streptococcal pharyngitis | General disorders | Systematic Assessment |
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| Respiratory virus (RSV) | General disorders | Systematic Assessment |
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| stomach ache | General disorders | Systematic Assessment |
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| vasovagal syndrome | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kyriakie Sarafoglou | University of Minnesota | 6126245965 | saraf010@umn.edu |
| Feb 21, 2024 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 17, 2021 | Feb 29, 2024 | ICF_001.pdf |
| ID | Term |
|---|---|
| D000312 | Adrenal Hyperplasia, Congenital |
| D006965 | Hyperplasia |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000308 | Adrenocortical Hyperfunction |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D000307 | Adrenal Gland Diseases |
| ID | Term |
|---|---|
| D047808 | Adrenogenital Syndrome |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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