Clinical trial NCT03936517: Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
Official title: Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Adrenal Insufficiency
Keywords: Glucocorticoids
Hydrocortisone
Prednisolone
Cortisol
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Imperial Health Charity
First posted: 2019-05-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two-arm, two-period, double-blind randomised crossover study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in concentration of Osteocalcin
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Secondary outcomes:
measure: Change in concentration of P1NP
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of BALP
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of NTX
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Heart Rate
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Systolic and diastolic blood pressure
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Waist-Hip circumference
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides)
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of high sensitivity CRP
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of Glucose
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Change in concentration of HbA1c
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Infection rates and severity
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Wellbeing assessed by completion the short form health survey
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
measure: Wellbeing assessed by completion the Addi-QoL questionnaire
timeFrame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
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: