Prednisolone in Adrenal Insufficiency Disease (PRED-AID)

• Research type

  Research Study

• Full title

  Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)

• IRAS ID

  201045

• Contact name

  Karim Meeran

• Contact email

  k.meeran@imperial.ac.uk

• Sponsor organisation

  Imperial College London

• Eudract number

  2018-001502-28

• Duration of Study in the UK

  4 years, 0 months, 1 days

• Research summary

  Steroid replacement therapy is vital for the health of patients with adrenal insufficiency (AI), who are unable to produce the natural stress hormone, cortisol. The objectives of steroid replacement therapy are to replace the body’s physiological requirements for cortisol without over-replacement and consequent Cushing’s syndrome. Equally, under-replacement presents the risk of patients experiencing potentially fatal Addisonian crises. Appropriately replacing a patient’s steroid requirement is a significant challenge.

  Hydrocortisone (HC) is used in the majority of patients with AI in the UK. However, HC has a short duration of action, necessitating dosing 3 times a day. Low-dose prednisolone (PR) is an alternative to HC which needs only once-daily. There have been no studies directly comparing low-dose PR to HC treatment.

  DESIGN: Two-arm, two-period, double-blind crossover study

  AIMS: To compare the effects of two routine treatments of adrenal insufficiency (AI), low dose prednisolone and standard regimens of hydrocortisone.

  OUTCOME MEASURES: The effects of both treatment regimens on the following will be compared:
  • Bone turnover
  • Cardiovascular risk
  • Glycaemic control
  • Infection rates and severity
  • Immunology profiles
  • Safety
  • Wellbeing
  • Compliance

  POPULATION: Patients with stably treated primary or secondary hypoadrenalism who are attending endocrinology clinics in the UK

  ELIGIBILITY: Patients able to give informed consent, between 18 and 70, who have been diagnosed with AI for over 6 months and have remained on a stable hormone replacement regimen for at least 3 months.

  TREATMENT AND DURATION: Either:

  a) Four months of prednisolone once daily followed by 4 months of hydrocortisone thrice daily or;
  b) Four months of hydrocortisone thrice daily followed by 4 months of prednisolone once daily

  The dose of the participant’s usual regimen will be unchanged from their pre-study dose. The dose of the alternative medication to be used will be elucidated prior to each participant’s enrolment on the study.

  Lay summary of study results: Both hydrocortisone and prednisolone are safe for the treatment of adrenal insufficiency. Neither drug showed preponderance for adverse effects, which were evenly distributed. There was no difference in subjective health as determined by the use of quality of life questionnaires.

  Prednisolone was associated with weight loss, reductions in waist circumference and BMI, and improvements in blood glucose control (measured by HbA1c). Bone markers were lower with prednisolone, indicating reduced formation and resorption of bone (which are normal bone processes). The meaning of the latter finding is not clear. It is however apparent that there is a difference between hydrocortisone and prednisolone when it comes to effect on bone.

  No other meaningful differences were seen in other biochemical cardiac or metabolic markers.

  Taken together, the results indicate that there may be cardiometabolic benefits to using prednisolone in adrenal insufficiency. This is evidenced by the weight reductions and improvements in glucose handling.

• REC name

  London - South East Research Ethics Committee

• REC reference

  19/LO/0083

• Date of REC Opinion

  25 Jan 2019

• REC opinion

  Favourable Opinion