Back to resultsSafety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study) (PRED-AID)
Primary Purpose
Adrenal Insufficiency
Status
Active
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Prednisolone
Hydrocortisone
Sponsored by
About this trial
This is an interventional treatment trial for Adrenal Insufficiency focused on measuring Glucocorticoids, Hydrocortisone, Prednisolone, Cortisol
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
Sites / Locations
- Imperial College Healthcare NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Prednisolone first; hydrocortisone second
Hydrocortisone first; prednisolone second
Arm Description
Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.
Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.
Outcomes
Primary Outcome Measures
Change in concentration of Osteocalcin
Assesses bone health of each group by comparing total osteocalcin and undercarboxylated osterocalcin
Secondary Outcome Measures
Change in concentration of P1NP
Assesses bone health of each group by comparing P1NP
Change in concentration of BALP
Assesses bone health of each group by comparing BALP
Change in concentration of NTX
Assesses bone health of each group by comparing NTX
Heart Rate
recording observations- heart rate
Systolic and diastolic blood pressure
recording observations- blood pressure
Waist-Hip circumference
recording observations- Waist-Hip circumference ratios
Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides)
measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides
Change in concentration of high sensitivity CRP
measuring biochemical indicators of cardiovascular risk: high sensitivity CRP
Change in concentration of Glucose
measuring glucose
Change in concentration of HbA1c
measuring HbA1c
Infection rates and severity
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
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
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.
Full Information
NCT ID
NCT03936517
First Posted
April 29, 2019
Last Updated
August 31, 2023
Sponsor
Imperial College London
Collaborators
National Institute for Health Research, United Kingdom, Imperial Health Charity
1. Study Identification
Unique Protocol Identification Number
NCT03936517
Brief Title
Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
Acronym
PRED-AID
Official Title
Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 31, 2019 (Actual)
Primary Completion Date
February 1, 2025 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
National Institute for Health Research, United Kingdom, Imperial Health Charity
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adrenal Insufficiency
Keywords
Glucocorticoids, Hydrocortisone, Prednisolone, Cortisol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Two-arm, two-period, double-blind randomised crossover study
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prednisolone first; hydrocortisone second
Arm Type
Other
Arm Description
Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.
Arm Title
Hydrocortisone first; prednisolone second
Arm Type
Other
Arm Description
Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Low dose prednisolone for the treatment of adrenal insufficiency. Usually administered once daily
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
Standard regimens of hydrocortisone for the treatment of adrenal insufficiency. Usually administered thrice daily.
Primary Outcome Measure Information:
Title
Change in concentration of Osteocalcin
Description
Assesses bone health of each group by comparing total osteocalcin and undercarboxylated osterocalcin
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Secondary Outcome Measure Information:
Title
Change in concentration of P1NP
Description
Assesses bone health of each group by comparing P1NP
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Change in concentration of BALP
Description
Assesses bone health of each group by comparing BALP
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Change in concentration of NTX
Description
Assesses bone health of each group by comparing NTX
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Heart Rate
Description
recording observations- heart rate
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Systolic and diastolic blood pressure
Description
recording observations- blood pressure
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Waist-Hip circumference
Description
recording observations- Waist-Hip circumference ratios
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides)
Description
measuring biochemical indicators of cardiovascular risk: 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.
Title
Change in concentration of high sensitivity CRP
Description
measuring biochemical indicators of cardiovascular risk: 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.
Title
Change in concentration of Glucose
Description
measuring glucose
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Change in concentration of HbA1c
Description
measuring HbA1c
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Infection rates and severity
Description
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.
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Wellbeing assessed by completion the short form health survey
Description
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.
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
Title
Wellbeing assessed by completion the Addi-QoL questionnaire
Description
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.
Time Frame
Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karim Meeran, MBBS BSc MD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imperial College Healthcare NHS Trust
City
London
ZIP/Postal Code
W12 8RF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of Prednisolone in Adrenal Insufficiency Disease (PRED-AID Study)
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