Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Addison Disease Clinical Trial

Official title:

Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096510
• Other study ID #: 2013/1738
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 27, 2014
• Est. completion date: December 2017

Study information

• Verified date: June 2024
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Addison Disease
• Adrenal Hyperplasia Congenital
• Adrenal Hyperplasia, Congenital
• Adrenocortical Hyperfunction
• Adrenogenital Syndrome
• Hyperplasia

Intervention

Drug:
• Solu-Cortef
administration by pump for minimum 2 weeks
• Cortef
tablet treatment 2 ro 3 times per day for 14 days

Locations

Country	Name	City	State
Norway	University Hospital Helse Bergen	Bergen

Sponsors (1)

Lead Sponsor	Collaborator
Haukeland University Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (4)

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. — View 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. — View 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. Erratum In: Eur J Endocrinol. 2008 Jun;158(6):939. Dosage error in article text. — View 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. E — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum cortisol -24 hours curve	admission to hospital for 24 hours	24 hours
Secondary	Salivary cortisol - 24 hours curve	admission to the hospital for 25 hours	24 hours
Secondary	24 h urine cortisol and metabolites	urine samples for 24 hours	24 hours
Secondary	levels of corticotropic hormone	blood samples	24 hours
Secondary	24 hours curve of tissue cortisol	The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)	24 hours
Secondary	gene expression	m RNA expression of genes	24 hours