Adrenal InsufficiencyPhase 4NCT03282487
Optimising Steroid Replacement in Patients With Adrenal Insufficiency
A Phase 4 study testing Modified release hydrocortisone in people with Adrenal Insufficiency, run by The Adelaide and Meath Hospital, incorporating The National Children's Hospital at 1 site in Ireland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- Modified release hydrocortisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIreland
- Study dates
- 5 Sep 2017to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Ireland1 site
Adelaide and Meath Hospital incorporating the National Childrens Hospital
Dublin
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Adrenal Insufficiency
- Being tested
- Modified release hydrocortisone
- Keywords
- cortisol, adrenal insufficiency, hypopituitarism, hydrocortisone
- Medical subject headings
- Adrenal Insufficiency, Hypopituitarism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified release hydrocortisoneDrug
Also called Plenadren
Patients will switch from their usual conventional immediate release hydrocortisone to daily dose equivalent of modified release hydrocortisone (Plenadren®)
| Study group | Role | What they receive |
|---|---|---|
| Conventional immediate release hydrocortisone | No intervention | Not described |
| Modified release Hydrocortisone | Active comparator | 12 weeks of modified release hydrocortisone (Plenadren) Receives: Drug: Modified release hydrocortisone |
| Healthy control group | No intervention | Same research laboratory measurements performed in a healthy control group for comparison to patient group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global corticosteroid metabolism
Urinary steroid metabolite profiles.
Measured: At baseline and after 12 weeks of Plenadren(intervention) treatment
Adipose tissue corticosteroid metabolism
Cortisol generation profile using adipose tissue microdialysis catheter
Measured: At baseline and after 12 weeks of Plenadren(intervention) treatment
Hepatic corticosteroid metabolism
Serum Cortisol generation profile
Measured: At baseline and after 12 weeks of Plenadren(intervention) treatment
Secondary outcomes (2)
Quality of Life questionnaires
Measured: At baseline and after 12 weeks of Plenadren(intervention) treatment
Potential biomarkers for adequacy of hydrocortisone replacement
Gene and protein expression of adipose tissue samples
Measured: At baseline and after 12 weeks of Plenadren(intervention) treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start5 Sep 2017
- Primary completionSep 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Adelaide and Meath Hospital, incorporating The National Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Mark Sherlock, The Adelaide and Meath Hospital, incorporating The National Children's Hospital
- Investigators
- Mark Sherlock, Principal investigator, Adelaide and Meath Hospital incorporating the national childrens hospital, Tallaght, Dublin, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03282487
- Sponsor's protocol ID
- 2016/09/05
- Status last verified
- Sep 2017
- First submitted
- 12 Sep 2017
- Last updated
- 14 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dineen RA, Martin-Grace J, Ahmed KMS, Taylor AE, Shaheen F, Schiffer L, Gilligan LC, Lavery GG, Frizelle I, Gunness A, Garrahy A, Hannon AM, Methlie P, Eystein SH, Stewart PM, Tomlinson JW, Hawley JM, Keevil BG, O'Reilly MW, Smith D, McDermott J, Healy ML, Agha A, Pazderska A, Gibney J, Behan LA, Thompson CJ, Arlt W, Sherlock M. Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3178-3189. doi: 10.1210/clinem/dgad370.
PubMed 37339332
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimising Steroid Replacement in Patients With Adrenal Insufficiency
- ClinicalTrials.gov ID
- NCT03282487
- Acronym / sponsor ID
- 2016/09/05
- Conditions
- Adrenal Insufficiency
- Keywords
- cortisol, adrenal insufficiency, hypopituitarism, hydrocortisone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- The Adelaide and Meath Hospital, incorporating The National Children's HospitalUniversity, hospital or other
- Study start
- 5 Sep 2017 (actual)
- Primary completion
- Sep 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 14 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Conventional immediate release hydrocortisone | No intervention | – |
| Modified release Hydrocortisone | Active comparator | Drug: Modified release hydrocortisone12 weeks of modified release hydrocortisone (Plenadren) |
| Healthy control group | No intervention | –Same research laboratory measurements performed in a healthy control group for comparison to patient group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified release hydrocortisoneAlso: PlenadrenPatients will switch from their usual conventional immediate release hydrocortisone to daily dose equivalent of modified release hydrocortisone (Plenadren®) | Drug | Modified release Hydrocortisone |
Primary outcome
Global corticosteroid metabolism
Time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment
Urinary steroid metabolite profiles.
Adipose tissue corticosteroid metabolism
Time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment
Cortisol generation profile using adipose tissue microdialysis catheter
Hepatic corticosteroid metabolism
Time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment
Serum Cortisol generation profile
2 secondary outcomes
Quality of Life questionnaires
Time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment
Potential biomarkers for adequacy of hydrocortisone replacement
Time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2017.
- Derived from this study: PubMed 37339332Dineen RA, Martin-Grace J, Ahmed KMS, Taylor AE, Shaheen F, Schiffer L, Gilligan LC, Lavery GG, Frizelle I, Gunness A, Garrahy A, Hannon AM, Methlie P, Eystein SH, Stewart PM, Tomlinson JW, Hawley JM, Keevil BG, O'Reilly MW, Smith D, McDermott J, Healy ML, Agha A, Pazderska A, Gibney J, Behan LA, Thompson CJ, Arlt W, Sherlock M. Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3178-3189. doi: 10.1210/clinem/dgad370.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Sherlock principal investigator
Adelaide and Meath Hospital incorporating the national childrens hospital, Tallaght, Dublin, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Modified release hydrocortisone in people with Adrenal Insufficiency, run by The Adelaide and Meath Hospital, incorporating The National Children's Hospital at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global corticosteroid metabolism (time frame: At baseline and after 12 weeks of Plenadren(intervention) treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03282487, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2017.