Clinical trial NCT02096510: Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
Official title: Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Addison Disease
Adrenal Hyperplasia Congenital
Keywords: Addison Disease
Adrenal Hyperplasia Congenital
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2014-03-26
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the effects of tablet treatment, circadian and combined circadian and ultradian subcutaneous hydrocortisone infusion on steroid metabolism and tissue responses to therapy.

Detailed description: The conventional glucocorticoid replacement therapy in primary adrenal insufficiency (Addison's disease) and congenital adrenal hyperplasia renders the cortisol levels unphysiological, which may cause symptoms and long-term complications. This therapeutical approach does not enable to restore physiological circadian and ultradian rhythm of glucocorticoids. Current studies conclude that constant or unphysiological administration of glucocorticoids leads to abnormal gene transcription and causes sides effect of glucocorticoids treatment and long standing complications Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion, which can mimic not only the normal diurnal cortisol rhythm, but potentially also the ultradian cadence.

This is a pilot trial with an open cross-over design of 3 x minimum 2 weeks in 10 patients comparing the effects of tablet treatment versus continuous subcutaneous hydrocortisone infusion versus ultradian subcutaneous hydrocortisone infusion on serum, salivary, tissue hormonal response and glucocorticoid related gene expression.

Eligibility criteria: Inclusion Criteria:

1. clinical diagnosis of primary adrenal insufficiency
2. Written informed consent

Exclusion Criteria:.

1. Diabetes mellitus
2. Severe cardiovascular disease
3. Active malignant disease
4. Pregnancy or breast feeding
5. treatment with interfering drugs
6. Intake of grapefruit juice

Primary outcomes:
measure: Serum cortisol -24 hours curve
timeFrame: 24 hours
Secondary outcomes:
measure: Salivary cortisol - 24 hours curve
timeFrame: 24 hours
measure: 24 h urine cortisol and metabolites
timeFrame: 24 hours
measure: levels of corticotropic hormone
timeFrame: 24 hours
measure: 24 hours curve of tissue cortisol
timeFrame: 24 hours
measure: gene expression
timeFrame: 24 hours
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: University Hospital Helse Bergen
Study officials:
affiliation: Universtity of Bergen
name: Katerina Simunkova, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helse Bergen
name: Kristian Løvås, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Lightman SL, Conway-Campbell BL. The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration. Nat Rev Neurosci. 2010 Oct;11(10):710-8. doi: 10.1038/nrn2914. Epub 2010 Sep 15.
citation: Lovas K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. 2007 Jul;157(1):109-12. doi: 10.1530/EJE-07-0052.
citation: Lightman SL, Windle RJ, Julian MD, Harbuz MS, Shanks N, Wood SA, Kershaw YM, Ingram CD. Significance of pulsatility in the HPA axis. Novartis Found Symp. 2000;227:244-57; discussion 257-60. doi: 10.1002/0470870796.ch14.
citation: Simunkova K, Lovas K, Methlie P, Jovanovic N, Bifulco E, Bronstad I, Lightman SL, Husebye ES, Oksnes M. Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency. Horm Metab Res. 2023 Jul;55(7):471-478. doi: 10.1055/a-2092-5228. Epub 2023 May 12.