Clinical trial NCT03608943: Hydrocortisone Vs Prednisolone in AI (HYPER-AID)
Official title: Hydrocortisone Versus Prednisolone for Treatment of Adrenal Insufficiency Disease (HYPER-AID Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adrenal Insufficiency
Keywords: glucocorticoids
prednisolone
hydrocortisone
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2018-08-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CROSSOVER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with either primary or secondary adrenal insufficiency who are currently receiving glucocorticoid replacement therapy with hydrocortisone or prednisolone.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: P1NP
timeFrame: Minimum 4 months of stable treatment
measure: NTX
timeFrame: Minimum 4 months of stable treatment
Secondary outcomes:
measure: Heart rate
timeFrame: Minimum 4 months of stable treatment
measure: Blood pressure
timeFrame: Minimum 4 months of stable treatment
measure: Waist-hip circumference
timeFrame: Minimum 4 months of stable treatment
measure: Lipid profile (Total cholesterol, HDL, LDL and triglycerides)
timeFrame: Minimum 4 months of stable treatment
measure: High sensitivity CRP
timeFrame: Minimum 4 months of stable treatment
measure: Glucose
timeFrame: Minimum 4 months of stable treatment
measure: HbA1c
timeFrame: Minimum 4 months of stable treatment
measure: Frequency and severity of steroid replacement related symptoms
timeFrame: Minimum 4 months of stable treatment
measure: Efficacy of replacement and wellbeing
timeFrame: Minimum 4 months of stable treatment
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Karim Meeran, MBBS BSc MD
role: PRINCIPAL_INVESTIGATOR
References: