Optimising Steroid Replacement in Patients With Adrenal Insufficiency
Primary Purpose
Adrenal Insufficiency
Status
Unknown status
Phase
Phase 4
Locations
Ireland
Study Type
Interventional
Intervention
Modified release hydrocortisone
Sponsored by
About this trial
This is an interventional treatment trial for Adrenal Insufficiency focused on measuring cortisol, adrenal insufficiency, hypopituitarism, hydrocortisone
Eligibility Criteria
Inclusion Criteria:
- Male or female patients ≥ 18years of age with Primary Adrenal Insufficiency (Addison's disease) confirmed on biochemical testing.
- Male or female patients ≥ 18years of age with ACTH deficiency defined by a stimulated peak cortisol in response to insulin-induced hypoglycaemia or short synacthen testing <400 nmol/l, with known organic pituitary disease, and no adjustment in hormone replacement for at least 3 months prior to study entry.
- Signed informed consent to participate in the study
Exclusion Criteria:
- Age < 18 years
- Patients with acute medical or surgical illness
- Patients with advanced cardiac/pulmonary disease
- Patients with a terminal illness
- Patients on glucocorticoids for purposes other than ACTH deficiency
- Patients on agents that interfere with corticosteroid metabolism
Sites / Locations
- Adelaide and Meath Hospital incorporating the National Childrens Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Active Comparator
No Intervention
Arm Label
Conventional immediate release hydrocortisone
Modified release Hydrocortisone
Healthy control group
Arm Description
12 weeks of modified release hydrocortisone (Plenadren)
Same research laboratory measurements performed in a healthy control group for comparison to patient group
Outcomes
Primary Outcome Measures
Global corticosteroid metabolism
Urinary steroid metabolite profiles.
Adipose tissue corticosteroid metabolism
Cortisol generation profile using adipose tissue microdialysis catheter
Hepatic corticosteroid metabolism
Serum Cortisol generation profile
Secondary Outcome Measures
Quality of Life questionnaires
Potential biomarkers for adequacy of hydrocortisone replacement
Gene and protein expression of adipose tissue samples
Full Information
NCT ID
NCT03282487
First Posted
September 12, 2017
Last Updated
September 12, 2017
Sponsor
The Adelaide and Meath Hospital, incorporating The National Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03282487
Brief Title
Optimising Steroid Replacement in Patients With Adrenal Insufficiency
Official Title
Optimising Steroid Replacement in Patients With Adrenal Insufficiency
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 5, 2017 (Actual)
Primary Completion Date
September 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Adelaide and Meath Hospital, incorporating The National Children's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Adrenal insufficiency is a condition where the adrenal glands do not produce an adequate amount of steroid hormones. The aetiology of adrenal insufficiency can be primary or secondary. Patients will adrenal insufficiency have increased morbidity and mortality. In recent years there has been concern regarding what is the optimal dose and regimen of steroid replacement for patients. Unfortunately there is no accurate way of monitoring if a patient is on too much or too little steroid. We have shown in hypopituitary patients with secondary adrenal insufficiency that higher doses of hydrocortisone may be harmful. This reason for this is not fully understood.
In recent years, a modified release hydrocortisone tablet (Plenadren) taken once per day (unlike conventional immediate release hydrocortisone which requires twice or thrice daily regimen) has come on the market. This tablet has shown to a have a steroid profile that more closely resembles normal physiology, avoiding the peak steroid levels that occur during thrice daily regimens, which may be of importance for improving outcome in adrenal insufficiency patients. It also shown improved cardiovascular risk factors, glucose metabolism and quality of life in compared to conventional treatment.
The aim of our study is to assess the effect of hydrocortisone therapy on how the body uses and breaks down (metabolises) steroids. This will be done by several different research methods: by measuring markers of steroid action and metabolism in blood, urine and within the fat tissue under the skin in the abdomen. These results will be compared in the same patient while on their usual hydrocortisone and after switching to modified release hydrocortisone for 12 weeks, and to results from a normal healthy control group who are not on steroid replacement.
This will be the first study to assess the impact of this new modified release hydrocortisone in relation to tissue steroid metabolism. The results will potentially help us to improve the treatment of patients with steroid deficiency and reduce the side effects seen in these patients.
Detailed Description
This is a prospective, cross-over study. This study cannot be blinded or placebo controlled due to the risk of adrenal crisis in the study population with primary and secondary adrenal insufficiency.
The aim of study is to assess the effect of immediate release and modified release hydrocortisone therapy on corticosteroid metabolism and 11-HSD1 in vivo (by assessment of urine metabolites and liver/ adipose tissue metabolism) by using several translational research approaches. This will also be compared to normal healthy controls to assess which treatment protocol is most physiological.
Study Objectives
To assess the effect of changing to modified release hydrocortisone therapy on global corticosteroid metabolism as assessed by urinary steroid metabolite profiles.
To assess the effect of changing to modified release hydrocortisone therapy on adipose tissue corticosteroid metabolism and action
To assess the effect of changing to modified release hydrocortisone on hepatic corticosteroid metabolism.
To assess the effect of changing to modified release hydrocortisone therapy on patient quality of life (QoL) as assessed through validated QoL questionnaires.
To compare results to normal healthy controls to assess which treatment protocol is most physiological.
To assess potential biomarkers for adequacy of hydrocortisone replacement therapy.
Patients will switch from their usual conventional immediate release hydrocortisone to daily dose equivalent of modified release hydrocortisone (Plenadren®) for 12 weeks.Other hormone replacement therapy regimens will not be adjusted during the study period.
Research laboratory measurements will be performed at baseline and 12 weeks of modified release hydrocortisone. At the end of the intervention treatment period, the patients will be shifted to their usual hydrocortisone treatment and will be followed at the outpatient clinic according to the directives of the clinic.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Insufficiency
Keywords
cortisol, adrenal insufficiency, hypopituitarism, hydrocortisone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Conventional immediate release hydrocortisone
Arm Type
No Intervention
Arm Title
Modified release Hydrocortisone
Arm Type
Active Comparator
Arm Description
12 weeks of modified release hydrocortisone (Plenadren)
Arm Title
Healthy control group
Arm Type
No Intervention
Arm Description
Same research laboratory measurements performed in a healthy control group for comparison to patient group
Intervention Type
Drug
Intervention Name(s)
Modified release hydrocortisone
Other Intervention Name(s)
Plenadren
Intervention Description
Patients will switch from their usual conventional immediate release hydrocortisone to daily dose equivalent of modified release hydrocortisone (Plenadren®)
Primary Outcome Measure Information:
Title
Global corticosteroid metabolism
Description
Urinary steroid metabolite profiles.
Time Frame
At baseline and after 12 weeks of Plenadren(intervention) treatment
Title
Adipose tissue corticosteroid metabolism
Description
Cortisol generation profile using adipose tissue microdialysis catheter
Time Frame
At baseline and after 12 weeks of Plenadren(intervention) treatment
Title
Hepatic corticosteroid metabolism
Description
Serum Cortisol generation profile
Time Frame
At baseline and after 12 weeks of Plenadren(intervention) treatment
Secondary Outcome Measure Information:
Title
Quality of Life questionnaires
Time Frame
At baseline and after 12 weeks of Plenadren(intervention) treatment
Title
Potential biomarkers for adequacy of hydrocortisone replacement
Description
Gene and protein expression of adipose tissue samples
Time Frame
At baseline and after 12 weeks of Plenadren(intervention) treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female patients ≥ 18years of age with Primary Adrenal Insufficiency (Addison's disease) confirmed on biochemical testing.
Male or female patients ≥ 18years of age with ACTH deficiency defined by a stimulated peak cortisol in response to insulin-induced hypoglycaemia or short synacthen testing <400 nmol/l, with known organic pituitary disease, and no adjustment in hormone replacement for at least 3 months prior to study entry.
Signed informed consent to participate in the study
Exclusion Criteria:
Age < 18 years
Patients with acute medical or surgical illness
Patients with advanced cardiac/pulmonary disease
Patients with a terminal illness
Patients on glucocorticoids for purposes other than ACTH deficiency
Patients on agents that interfere with corticosteroid metabolism
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Sherlock
Organizational Affiliation
Adelaide and Meath Hospital incorporating the national childrens hospital, Tallaght, Dublin, Ireland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Adelaide and Meath Hospital incorporating the National Childrens Hospital
City
Dublin
Country
Ireland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Optimising Steroid Replacement in Patients With Adrenal Insufficiency
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