Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Change in concentration of Osteocalcin
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will be randomised to one of two arms: A) prednisolone in the first treatment period and hydrocortisone in the second period; or B) hydrocortisone in the first treatment period and prednisolone in the second period.
Blinding will be achieved by providing participants with a tablet three times a day regardless of the treatment they are currently on. If on a hydrocortisone treatment period, the participant will receive tablets of hydrocortisone at their personally tailored dose three times a day (morning, noon and afternoon). When on prednisolone, the participant will receive a prednisolone tablet in the morning (at their personal dose), followed by a matched placebo at noon and in the afternoon. The tablets used in the study have been specifically made for the study to maintain blinding.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Prednisolone first; hydrocortisone second
Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.
干预措施: Prednisolone (Drug)
Prednisolone first; hydrocortisone second
Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.
干预措施: Hydrocortisone (Drug)
Hydrocortisone first; prednisolone second
Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.
干预措施: Prednisolone (Drug)
Hydrocortisone first; prednisolone second
Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Change in concentration of Osteocalcin
时间窗: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Assesses bone health of each group by comparing total osteocalcin and undercarboxylated osterocalcin
次要结局
- Change in concentration of P1NP(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of BALP(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of NTX(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Heart Rate(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Systolic and diastolic blood pressure(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Waist-Hip circumference(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of HbA1c(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Infection rates and severity(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Wellbeing assessed by completion the short form health survey(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Wellbeing assessed by completion the Addi-QoL questionnaire(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides)(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of high sensitivity CRP(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)
- Change in concentration of Glucose(Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.)