Hydrocortisone Vs Prednisolone in AI (HYPER-AID)

Study Overview
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Brief Summary
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This study is designed to collect data on individuals with adrenal insufficiency who are changing treatments from hydrocortisone to prednisolone, or vice versa. It will compare anthropometric, biochemical and subjective health outcomes between both treatments.

Detailed Description
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In the UK, oral immediate release hydrocortisone divided in three doses daily has been the traditional treatment. The most common regimen in clinical practice uses doses of 10 mg on waking, 5 mg at lunch time and 5 mg in the afternoon. Once daily prednisolone is another regimen in clinical use and now prescribed at less than 5mg daily. It has a longer duration of action and a smoother pharmacokinetic profile compared to hydrocortisone. Moreover, prednisolone is much more cost-effective than hydrocortisone with 5mg tablets. Prednisolone is less commonly used due to perceived concerns regarding loss of bone mineral density leading to osteoporosis, increased insulin resistance leading to steroid induced diabetes, and rises in blood pressure and weight leading to increased cardiovascular risk. This belief is perhaps driven by the fact that most clinicians encounter prednisolone in the context of the treatment of asthma, rheumatoid arthritis etc. where far higher doses are employed. Where effects on bone health have been noted, they have been in association with higher doses of prednisolone (7.5mg) than those employed today (2-5mg). Although conventionally prednisolone 5 mg is assumed to be bioequivalent to HC 20 mg (ratio 1:4), newer studies suggest that the ratio may be nearer 1:6-8 i.e. lower doses can be used.

Official Title
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Hydrocortisone Versus Prednisolone for Treatment of Adrenal Insufficiency Disease (HYPER-AID Study)

Conditions
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Adrenal Insufficiency

Intervention / Treatment
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* Other: There is no specific intervention other than an individual changing their treatment as part of their usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 - 85 years Male or female Diagnosed with adrenal insufficiency (AI) for over 6 months according to standard diagnostic criteria Established on stable hydrocortisone or prednisolone replacement, dose not altered for at least 4 months Individuals taking other hormone replacements are accepted providing that their replacement doses have not altered for at least 3 months; Individuals who are able and willing to give written informed consent to participate in the study Exclusion Criteria: Individuals who are unable to give informed consent Pregnancy (determined by patients self-reporting pregnancy status) Patients using the combined oral contraceptive pill

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adrenal insufficiency<br>Individuals who are in the process of changing their treatment from: hydrocortisone to prednisolone or; prednisolone to hydrocortisone | Other: There is no specific intervention other than an individual changing their treatment as part of their usual care<br>* There is no specific intervention other than an individual changing their treatment as part of their usual care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P1NP | measurement of bone turnover markers: P1NP, | Minimum 4 months of stable treatment | 
| NTX | measurement of bone turnover markers: NTX | Minimum 4 months of stable treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | recording observations- heart rate | Minimum 4 months of stable treatment | 
| Blood pressure | recording observations- blood pressure | Minimum 4 months of stable treatment | 
| Waist-hip circumference | recording observations- waist-hip circumference ratios | Minimum 4 months of stable treatment | 
| Lipid profile (Total cholesterol, HDL, LDL and triglycerides) | measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides | Minimum 4 months of stable treatment | 
| High sensitivity CRP | measuring biochemical indicators of cardiovascular risk: high sensitivity CRP | Minimum 4 months of stable treatment | 
| Glucose | assessed by measuring glucose | Minimum 4 months of stable treatment | 
| HbA1c | assessed by measuring HBA1c | Minimum 4 months of stable treatment | 
| Frequency and severity of steroid replacement related symptoms | assessed by reporting of symptoms of steroid deficiency, their frequency and severity stratified by the patient's current replacement regimen. Symptoms include nausea, lethargy, muscle pain, headaches etc.) | Minimum 4 months of stable treatment | 
| Efficacy of replacement and wellbeing | assessed using subjective health questionnaire | Minimum 4 months of stable treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucocorticoids, prednisolone, hydrocortisone