Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
Information source: Haukeland University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Addison Disease; Adrenal Hyperplasia Congenital
Intervention: Solu-Cortef (Drug); Cortef (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Haukeland University Hospital Official(s) and/or principal investigator(s): Katerina Simunkova, MD, PhD, Principal Investigator, Affiliation: Universtity of Bergen Kristian Løvås, MD, PhD, Study Director, Affiliation: Helse Bergen
Overall contact: Kristian Løvås, MD, PhD, Phone: 55973075, Email: kristian.lovas@helse-bergen.no
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.
Clinical Details
Official title: Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Serum cortisol -24 hours curve
Secondary outcome: Salivary cortisol - 24 hours curve24 h urine cortisol and metabolites levels of corticotropic hormone 24 hours curve of tissue cortisol gene expression
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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Kristian Løvås, MD, PhD, Phone: 55973075, Email: kristian.lovas@helse-bergen.no
University Hospital Helse Bergen, Bergen 5021, Norway; Recruiting Katerina Simunkova, MD, PhD, Phone: 41079948, Email: katerina.simunkova@k2.uib.no Kristian Løvås, MD, PhD, Phone: 55973075, Email: kristian.lovas@helse-bergen.no Kristian Løvås, MD, PhD, Sub-Investigator Katerina Simunkova, MD, PhD, Principal Investigator
Additional Information
Related publications: 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. Løvås K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. 2007 Jul;157(1):109-12. Erratum in: Eur J Endocrinol. 2008 Jun;158(6):939. Dosage error in article text. 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. Review.
Starting date: August 2014
Last updated: March 27, 2015
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