# Ph2a SQ HC infusion pump in congenital adrenal hyperplasia IND125,640 (9/15/2017)

> **NIH FDA R01** · UNIVERSITY OF MINNESOTA · 2020 · $499,999

## Abstract

ABSTRACT
Congenital adrenal hyperplasia (CAH) is a form of adrenal insufficiency characterized by impaired cortisol
synthesis and excessive adrenal androgen production. Children with CAH under the recommended oral
hydrocortisone therapy are repeatedly exposed to the undesirable states of hypocortisolemia and
hypercortisolemia. Hypocortisolemia triggers increased production of 17-hydroxyprogesterone (17OHP) and
adrenal androgen (androstenedione; D4A), which can lead premature fusion of the growth plates, genital
virilization, precocious puberty, adrenal rests, polycystic ovarian syndrome and infertility. Hypercortisolemia
also has untoward long term effects, such as osteoporosis, short stature, and increased risk for developing
metabolic syndrome-related atherosclerotic cardiovascular disease in adult life. Current oral hydrocortisone
therapy is suboptimal as it does not replicate the pulsatile daily patterns of both circadian and ultradian cortisol
secretion rhythms. As such, even patients on physiological doses experience adverse outcomes. Therefore, an
improved and personalized drug delivery system that more closely replicates physiological pulsatile cortisol
secretion and limits periods of hypo- and hypercortisolemia in children is needed. Our long term goal is to
improve clinical outcomes in children with CAH through optimizing the dosing and scheduling of replacement
therapy and avoid the hyperandrogenemia that is specific to CAH. This study's objective is to demonstrate
that pulsatile SQHC pump delivery more closely replicates circadian and ultradian rhythms of cortisol and
improves control of adrenal androgens. Our study's rationale is that cortisol profiles more consistent with
physiologic rhythms of cortisol secretion will produce better health outcomes. Our specific aim is to design and
implement an individualized pulsatile SQHC pump regimen that will more closely mimic cortisol circadian and
ultradian rhythms in order to reduce the length of time a patient experiences hyper- and hypocortisolemia, and
extend the duration of time 17OHP and D4A serum concentrations remain in an acceptable range. This is the
first clinical trial in children with CAH that uses a pulsatile SQHC delivery system. Our approach is innovative
as it is a substantive departure from the standard of care that could not only significantly improve long-term
outcomes of patients with CAH, but also alter our fundamental approach to glucocorticoid dosing of patients
with adrenal insufficiency of other etiologies, thus spurring development of novel methods of hormonal drug
delivery, and stimulating new lines of investigation in physiological systems with tightly controlled feedback
loops.

## Key facts

- **NIH application ID:** 9766097
- **Project number:** 5R01FD006100-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Richard C Brundage
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $499,999
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9766097

## Citation

> US National Institutes of Health, RePORTER application 9766097, Ph2a SQ HC infusion pump in congenital adrenal hyperplasia IND125,640 (9/15/2017) (5R01FD006100-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9766097. Licensed CC0.

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