Hydrocortisone Vs Prednisolone in AI (HYPER-AID) (HYPER-AID)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Other: There is no specific intervention other than an individual changing their treatment as part of their usual care

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Sirazum Choudhury, MBBS MRCP; Phone Number: 07555717544; Email: steroids@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W12 8RF
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Sirazum Choudhury, MBBS BSc; Phone Number: 07555717544; Email: steroids@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Crossover
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adrenal insufficiency; 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; There is no specific intervention other than an individual changing their treatment as part of their usual care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Karim Meeran, MBBS BSc MD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 18, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: hydrocortisone; glucocorticoids; prednisolone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency
• Other Study ID Numbers: 18HH4457; 234243 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are currently no plans to share individual data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No