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

Imperial College London

Status and phase: Active, not recruiting; Phase 3

Conditions: Adrenal Insufficiency

Treatments: Drug: Prednisolone; Drug: Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT03936517

201045 (Other Identifier)

19/LO/0083 (Other Identifier)

2018-001502-28 (EudraCT Number)

ISRCTN41325341 (Registry Identifier)

18IC4546

Details and patient eligibility

About

This study compares low-dose prednisolone therapy against standard regimens of hydrocortisone therapy for the treatment of adrenal insufficiency (AI). AI is a condition in which, individuals are unable to sufficiently produce the natural stress hormone, cortisol.

Full description

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.

This is a two-arm, two-period, double-blind, randomised, cross-over study comparing the low dose PR and standard regimens of HC in the treatment of AI.

Enrollment: 44 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 18 - 70 years
• Male or female
• Diagnosed with AI for over 6 months according to standard diagnostic criteria
• Established on stable HC replacement or prednisolone replacement, dose not altered for at least 3 months
• Established on a stable dose of Fludrocortisone, if taking, dose not altered for at least 3 months
• Participants taking other hormone replacements (e.g. levothyroxine, testosterone or growth hormone in secondary adrenal insufficiency) are accepted providing that their replacement doses have not altered for at least 3 months
• Participants who are otherwise healthy enough to participate, as determined by pre-study medical history and physical examination.
• Participants who are able and willing to give written informed consent to participate in the study.

Exclusion criteria

• Participants with a diagnosis of Type 1 or Type 2 diabetes mellitus.
• Unable to give informed consent.
• Taking supplements or herbal medications that the participant is unwilling or unable to stop prior to and during the study period e.g. St John's Wort (may decrease prednisolone levels), Cat's claw, Echinacea (immunomodulatory properties).
• Currently taking medications that alter CYP3A4 metabolism of glucocorticoids that the participant is unwilling or unable to stop prior to and during the study period e.g. phenytoin, phenobarbital, rifampicin, rifabutin, carbamazepine, primidone, aminoglutethimide, itraconazole, ketoconazole, ciclosporin or ritonavir.
• Pregnancy, taking the combined oral contraceptive pill, or oral oestrogen replacement therapy due to the effects on cortisol binding globulin levels and determination of prednisolone levels. Transdermal oestrogen replacement is permitted.
• Diagnosis of congenital adrenal hyperplasia, untreated

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups

Prednisolone first; hydrocortisone second

Other group

Description:

Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.

Treatment:

Drug: Hydrocortisone

Drug: Prednisolone

Hydrocortisone first; prednisolone second

Other group

Description:

Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.

Treatment:

Drug: Hydrocortisone

Drug: Prednisolone