Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

• Sponsor: Haukeland University Hospital (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT02096510
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 3
• Duration (Months): 40
• Patients Per Site Per Month: 0.2

Study Details

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

• Study Type: Interventional
• Anticipated 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: Aug 1, 2014
• Anticipated Primary Completion Date: Dec 1, 2017
• Anticipated Study Completion Date: Dec 1, 2017

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 Names: hydrocortisone ; Drug: Cortef; tablet treatment 2 ro 3 times per day for 14 days; Other Names: 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 Names: hydrocortisone ; Drug: Cortef; tablet treatment 2 ro 3 times per day for 14 days; Other Names: 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 Names: hydrocortisone ; Drug: Cortef; tablet treatment 2 ro 3 times per day for 14 days; Other Names: hydrocortisone tablets

Outcome Measures

Primary Outcome Measures

1. Serum cortisol -24 hours curve [24 hours]

   admission to hospital for 24 hours

Secondary Outcome Measures

1. Salivary cortisol - 24 hours curve [24 hours]

   admission to the hospital for 25 hours

2. 24 h urine cortisol and metabolites [24 hours]

   urine samples for 24 hours

3. levels of corticotropic hormone [24 hours]

   blood samples

4. 24 hours curve of tissue cortisol [24 hours]

   The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)

5. gene expression [24 hours]

   m RNA expression of genes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Helse Bergen	Bergen		Norway	5021

Sponsors and Collaborators

• Haukeland University Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

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.
• 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.
• 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.

• Responsible Party: Haukeland University Hospital
• ClinicalTrials.gov Identifier: NCT02096510
• Other Study ID Numbers: 2013/1738
• First Posted: Mar 26, 2014
• Last Update Posted: Dec 21, 2016
• Last Verified: Dec 1, 2016

• Keywords provided by Haukeland University Hospital: Addison Disease; Adrenal Hyperplasia Congenital
• Additional relevant MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Addison Disease; Hyperplasia; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate

Study Results

No Results Posted as of Dec 21, 2016