免费获得国外相关药品，最快 1 个工作日回馈药物信息
出境医 / 临床实验 / Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) (PRED-AID)
Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) (PRED-AID)
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adrenal Insufficiency | Drug: Prednisolone Drug: Hydrocortisone | Phase 3 |
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.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 44 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | Two-arm, two-period, double-blind randomised crossover study |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | 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. |
| Primary Purpose: | Treatment |
| Official Title: | Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) |
| Actual Study Start Date : | July 31, 2019 |
| Estimated Primary Completion Date : | February 1, 2023 |
| Estimated Study Completion Date : | February 1, 2023 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
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.
|
Drug: Prednisolone
Low dose prednisolone for the treatment of adrenal insufficiency. Usually administered once daily
Drug: Hydrocortisone Standard regimens of hydrocortisone for the treatment of adrenal insufficiency. Usually administered thrice daily.
|
|
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.
|
Drug: Prednisolone
Low dose prednisolone for the treatment of adrenal insufficiency. Usually administered once daily
Drug: Hydrocortisone Standard regimens of hydrocortisone for the treatment of adrenal insufficiency. Usually administered thrice daily.
|
Outcome Measures
Primary Outcome Measures :
- Change in concentration of Osteocalcin [ Time Frame: 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
Secondary Outcome Measures :
- Change in concentration of P1NP [ Time Frame: 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 P1NP
- Change in concentration of BALP [ Time Frame: 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 BALP
- Change in concentration of NTX [ Time Frame: 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 NTX
- Heart Rate [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]recording observations- heart rate
- Systolic and diastolic blood pressure [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]recording observations- blood pressure
- Waist-Hip circumference [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]recording observations- Waist-Hip circumference ratios
- Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides) [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides
- Change in concentration of high sensitivity CRP [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]measuring biochemical indicators of cardiovascular risk: high sensitivity CRP
- Change in concentration of Glucose [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]measuring glucose
- Change in concentration of HbA1c [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]measuring HbA1c
- Infection rates and severity [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]assessed by completion of the German National Cohort Questionnaire (GNCQ). Frequency (None; 1; 2; 3; >3; Unknown) of 1. Upper respiratory tract infections; 2. Lower respiratory tract infections; 3.Gastroenteritis; 4. Mucosal infections; 5. Urinary tract infections; 6. Influenza; will be recorded. The frequencies of each type of infection will be compared between time points.
- Wellbeing assessed by completion the short form health survey [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]assessed by completion the short form health survey-36 (SF-36). Scores will be produced in each of 8 domains (Physical functioning, Role functioning/physical, Role functioning/emotional, Energy/fatigue, Emotional wellbeing, Social functioning, Pain, General Health and Health Change). Each domain is scored from 0 to 100, with higher scores suggesting more positive outcomes. Scores will be compared in each domain between time points.
- Wellbeing assessed by completion the Addi-QoL questionnaire [ Time Frame: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2. ]assessed by completion the Addi-QoL questionnaire. A total score between 30 and 120 is produced, with higher scores suggesting a more positive outcome. The score is compared between time points.
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Contacts
| Contact: Sirazum Choudhury, MBBS BSc | 07555717544 | steroids@imperial.ac.uk |
Locations
| United Kingdom | |
| Imperial College Healthcare NHS Trust | Recruiting |
| London, United Kingdom, W12 8RF | |
| Contact: Sirazum Choudhury, MBBS BSc 07555717544 steroids@imperial.ac.uk | |
Sponsors and Collaborators
Imperial College London
National Institute for Health Research, United Kingdom
Imperial Health Charity
Investigators
| Principal Investigator: | Karim Meeran, MBBS BSc MD | Imperial College London |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 29, 2019 | ||||
| First Posted Date ICMJE | May 3, 2019 | ||||
| Last Update Posted Date | August 14, 2019 | ||||
| Actual Study Start Date ICMJE | July 31, 2019 | ||||
| Estimated Primary Completion Date | February 1, 2023 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Change in concentration of Osteocalcin [ Time Frame: 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
|
||||
| Original Primary Outcome Measures ICMJE |
Osteocalcin [ Time Frame: 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
|
||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
|
||||
| Original Secondary Outcome Measures ICMJE |
|
||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) | ||||
| Official Title ICMJE | Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) | ||||
| 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. |
||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 3 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: Two-arm, two-period, double-blind randomised crossover study Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: 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. |
||||
| Condition ICMJE | Adrenal Insufficiency | ||||
| Intervention ICMJE |
|
||||
| Study Arms ICMJE |
|
||||
| Publications * | Not Provided | ||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
44 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | February 1, 2023 | ||||
| Estimated Primary Completion Date | February 1, 2023 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||
| Sex/Gender ICMJE |
|
||||
| Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
|
||||
| Listed Location Countries ICMJE | United Kingdom | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03936517 | ||||
| Other Study ID Numbers ICMJE | 18IC4546 2018-001502-28 ( EudraCT Number ) 201045 ( Other Identifier: IRAS ) ISRCTN41325341 ( Registry Identifier: ISRCTN ) 19/LO/0083 ( Other Identifier: Research Ethics Committee ) |
||||
| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
|
||||
| IPD Sharing Statement ICMJE |
|
||||
| Responsible Party | Imperial College London | ||||
| Study Sponsor ICMJE | Imperial College London | ||||
| Collaborators ICMJE |
|
||||
| Investigators ICMJE |
|
||||
| PRS Account | Imperial College London | ||||
| Verification Date | August 2019 | ||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||
