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Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

Primary Purpose

Addison Disease, Adrenal Hyperplasia Congenital

Status
Unknown status
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Solu-Cortef
Cortef
Sponsored by
Haukeland University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Addison Disease focused on measuring Addison Disease, Adrenal Hyperplasia Congenital

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Helse BergenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

continuous subcutaneous hydrocortisone

cortef tablets

ultradian subcutaneous hydrocortisone

Arm Description

continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate

the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.

ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate

Outcomes

Primary Outcome Measures

Serum cortisol -24 hours curve
admission to hospital for 24 hours

Secondary Outcome Measures

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

Full Information

First Posted
November 28, 2013
Last Updated
December 20, 2016
Sponsor
Haukeland University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02096510
Brief Title
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

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haukeland University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Addison Disease, Adrenal Hyperplasia Congenital
Keywords
Addison Disease, Adrenal Hyperplasia Congenital

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
continuous subcutaneous hydrocortisone
Arm Type
Experimental
Arm Description
continuous subcutaneous hydrocortisone infusion (CSHI), Solu-Cortef ® 50mg/ml infusate
Arm Title
cortef tablets
Arm Type
Active Comparator
Arm Description
the patient regular treatment by Cortef 5 mg, produced by Nycomed Pharma two times or three times a day.
Arm Title
ultradian subcutaneous hydrocortisone
Arm Type
Experimental
Arm Description
ultradian subcutaneous hydrocortisone infusion, Solu-Cortef ® 50mg/ml infusate
Intervention Type
Drug
Intervention Name(s)
Solu-Cortef
Other Intervention Name(s)
hydrocortisone
Intervention Description
administration by pump for minimum 2 weeks
Intervention Type
Drug
Intervention Name(s)
Cortef
Other Intervention Name(s)
hydrocortisone tablets
Intervention Description
tablet treatment 2 ro 3 times per day for 14 days
Primary Outcome Measure Information:
Title
Serum cortisol -24 hours curve
Description
admission to hospital for 24 hours
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Salivary cortisol - 24 hours curve
Description
admission to the hospital for 25 hours
Time Frame
24 hours
Title
24 h urine cortisol and metabolites
Description
urine samples for 24 hours
Time Frame
24 hours
Title
levels of corticotropic hormone
Description
blood samples
Time Frame
24 hours
Title
24 hours curve of tissue cortisol
Description
The tissue effect of glucocorticoid replacement - 24 hours curve of tissue cortisol (microdialysis)
Time Frame
24 hours
Title
gene expression
Description
m RNA expression of genes
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristian Løvås, MD, PhD
Phone
55973075
Email
kristian.lovas@helse-bergen.no
First Name & Middle Initial & Last Name or Official Title & Degree
Katerina Simunkova, MD, PhD
Phone
41079948
Email
katerina.simunkova@k2.uib.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katerina Simunkova, MD, PhD
Organizational Affiliation
Universtity of Bergen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kristian Løvås, MD, PhD
Organizational Affiliation
Helse Bergen
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital Helse Bergen
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katerina Simunkova, MD, PhD
Phone
41079948
Email
katerina.simunkova@k2.uib.no
First Name & Middle Initial & Last Name & Degree
Kristian Løvås, MD, PhD
Phone
55973075
Email
kristian.lovas@helse-bergen.no
First Name & Middle Initial & Last Name & Degree
Kristian Løvås, MD, PhD
First Name & Middle Initial & Last Name & Degree
Katerina Simunkova, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
20842176
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.
Results Reference
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PubMed Identifier
17609409
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.
Results Reference
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PubMed Identifier
10752074
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.
Results Reference
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Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia

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