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Adrenal InsufficiencyPhase 3PRED-AIDNCT03936517

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

A Phase 3 study testing Prednisolone and Hydrocortisone in people with Adrenal Insufficiency, run by Imperial College London at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Adrenal Insufficiency
What is being tested?
Prednisolone and Hydrocortisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited Kingdom
Study dates
31 Jul 2019to 1 Feb 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Imperial College Healthcare NHS Trust

    London, W12 8RF

Other trials in United Kingdom

About this study

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.

Read the 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.

Keywords
Glucocorticoids, Hydrocortisone, Prednisolone, Cortisol
Medical subject headings
Adrenal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrednisoloneDrug

    Low dose prednisolone for the treatment of adrenal insufficiency. Usually administered once daily

  • HydrocortisoneDrug

    Standard regimens of hydrocortisone for the treatment of adrenal insufficiency. Usually administered thrice daily.

Study groups in NCT03936517
Study groupRoleWhat they receive
Prednisolone first; hydrocortisone secondOtherParticipant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.
Receives: Drug: Prednisolone; Drug: Hydrocortisone
Hydrocortisone first; prednisolone secondOtherParticipant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.
Receives: Drug: Prednisolone; Drug: Hydrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in concentration of Osteocalcin

    Assesses bone health of each group by comparing total osteocalcin and undercarboxylated osterocalcin

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

Secondary outcomes (13)

  1. Change in concentration of P1NP

    Assesses bone health of each group by comparing P1NP

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  2. Change in concentration of BALP

    Assesses bone health of each group by comparing BALP

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  3. Change in concentration of NTX

    Assesses bone health of each group by comparing NTX

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  4. Heart Rate

    recording observations- heart rate

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  5. Systolic and diastolic blood pressure

    recording observations- blood pressure

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  6. Waist-Hip circumference

    recording observations- Waist-Hip circumference ratios

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  7. Change in concentration of Lipid profile (Total cholesterol, HDL, LDL and triglycerides)

    measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  8. Change in concentration of high sensitivity CRP

    measuring biochemical indicators of cardiovascular risk: high sensitivity CRP

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  9. Change in concentration of Glucose

    measuring glucose

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  10. Change in concentration of HbA1c

    measuring HbA1c

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  11. 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.

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  12. 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.

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

  13. 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.

    Measured: Between Day 1 and Day 120 within each study period; and between Day 120 of Period 1 and Period 2.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2019
  2. Study start31 Jul 2019
  3. Primary completion1 Feb 2025 (estimated)
  4. Study completion1 Feb 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Two-arm, two-period, double-blind randomised crossover study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03936517
Sponsor's protocol ID
18IC4546
Other IDs
2018-001502-28, 201045, ISRCTN41325341, 19/LO/0083, 2018
Acronym
PRED-AID
Status last verified
Aug 2023
First submitted
29 Apr 2019
Last updated
1 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Choudhury S, Lazarus K, Sharma A, Narula K, Go C, Cro S, Thaventhiran T, Khoo B, Tan T, Meeran K. Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism: A Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e262982. doi: 10.1001/jamanetworkopen.2026.2982.

    PubMed 41874506

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Prednisolone and Hydrocortisone in people with Adrenal Insufficiency, run by Imperial College London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03936517, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.

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