Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

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ClinicalTrials.gov Identifier: NCT02096510

Recruitment Status : Unknown

Verified December 2016 by Haukeland University Hospital.
Recruitment status was: Recruiting

First Posted : March 26, 2014

Last Update Posted : December 21, 2016

Sponsor:

Information provided by (Responsible Party):

Haukeland University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Addison Disease Adrenal Hyperplasia Congenital	Drug: Solu-Cortef Drug: Cortef	Phase 1 Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	10 participants
Allocation:	Non-Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
Study Start Date :	August 2014
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	December 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency 21-hydroxylase deficiency 17 alpha-hydroxylase/17,20-lyase deficiency Autoimmune Addison disease 3-beta-hydroxysteroid dehydrogenase deficiency

MedlinePlus related topics: Addison Disease

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Hydrocortisone valerate Hydrocortisone probutate Proctofoam-HC

Genetic and Rare Diseases Information Center resources: Addison's Disease 21-hydroxylase Deficiency Congenital Adrenal Hyperplasia Hyperadrenalism

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: continuous subcutaneous hydrocortisone continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate	Drug: Solu-Cortef administration by pump for minimum 2 weeks Other Name: hydrocortisone Drug: Cortef tablet treatment 2 ro 3 times per day for 14 days Other Name: hydrocortisone tablets
Active Comparator: cortef tablets the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.	Drug: Solu-Cortef administration by pump for minimum 2 weeks Other Name: hydrocortisone Drug: Cortef tablet treatment 2 ro 3 times per day for 14 days Other Name: hydrocortisone tablets
Experimental: ultradian subcutaneous hydrocortisone ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate	Drug: Solu-Cortef administration by pump for minimum 2 weeks Other Name: hydrocortisone Drug: Cortef tablet treatment 2 ro 3 times per day for 14 days Other Name: hydrocortisone tablets

Outcome Measures

Primary Outcome Measures :

Serum cortisol -24 hours curve [ Time Frame: 24 hours ]
admission to hospital for 24 hours

Secondary Outcome Measures :

Salivary cortisol - 24 hours curve [ Time Frame: 24 hours ]
admission to the hospital for 25 hours
24 h urine cortisol and metabolites [ Time Frame: 24 hours ]
urine samples for 24 hours
levels of corticotropic hormone [ Time Frame: 24 hours ]
blood samples
24 hours curve of tissue cortisol [ Time Frame: 24 hours ]
The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)
gene expression [ Time Frame: 24 hours ]
m RNA expression of genes

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

clinical diagnosis of primary adrenal insufficiency
Written informed consent

Exclusion Criteria:.

Diabetes mellitus
Severe cardiovascular disease
Active malignant disease
Pregnancy or breast feeding
treatment with interfering drugs
Intake of grapefruit juice

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02096510

Contacts

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Contact: Kristian Løvås, MD, PhD	55973075	kristian.lovas@helse-bergen.no
Contact: Katerina Simunkova, MD, PhD	41079948	katerina.simunkova@k2.uib.no

Locations

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Norway
University Hospital Helse Bergen	Recruiting
Bergen, Norway, 5021
Contact: Katerina Simunkova, MD, PhD 41079948 katerina.simunkova@k2.uib.no
Contact: Kristian Løvås, MD, PhD 55973075 kristian.lovas@helse-bergen.no
Sub-Investigator: Kristian Løvås, MD, PhD
Principal Investigator: Katerina Simunkova, MD, PhD

Sponsors and Collaborators

Haukeland University Hospital

Investigators

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Principal Investigator:	Katerina Simunkova, MD, PhD	Universtity of Bergen
Study Director:	Kristian Løvås, MD, PhD	Helse Bergen

More Information

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. Review.

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.

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Responsible Party:	Haukeland University Hospital
ClinicalTrials.gov Identifier:	NCT02096510
Other Study ID Numbers:	2013/1738
First Posted:	March 26, 2014 Key Record Dates
Last Update Posted:	December 21, 2016
Last Verified:	December 2016

Keywords provided by Haukeland University Hospital:


Addison Disease Adrenal Hyperplasia Congenital

Additional relevant MeSH terms:

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Adrenal Hyperplasia, Congenital Adrenogenital Syndrome Adrenocortical Hyperfunction Addison Disease Hyperplasia Pathologic Processes Disorders of Sex Development Urogenital Abnormalities Congenital Abnormalities Genetic Diseases, Inborn Steroid Metabolism, Inborn Errors Metabolism, Inborn Errors	Metabolic Diseases Adrenal Gland Diseases Endocrine System Diseases Gonadal Disorders Adrenal Insufficiency Autoimmune Diseases Immune System Diseases Hydrocortisone Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Hydrocortisone hemisuccinate Anti-Inflammatory Agents

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