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

NCT03936517 | Unknown Phase 3 DMC

• 5 other identifiers: 18IC45462018-001502-28201045ISRCTN4132534119/LO/0083
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Adrenal Insufficiency

Keywords

Glucocorticoids; Hydrocortisone; Prednisolone; Cortisol

Outcome Measures

Primary Outcomes (1)

• Change in concentration of Osteocalcin

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

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

Secondary Outcomes (13)

• 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.

Study Arms (2)

Prednisolone first; hydrocortisone second

OTHER

Participant will receive 4 months of prednisolone in the first study period and 4 months of hydrocortisone in the second study period.

Drug: Prednisolone; Drug: Hydrocortisone

Hydrocortisone first; prednisolone second

OTHER

Participant will receive 4 months of hydrocortisone in the first study period and 4 months of prednisolone in the second study period.

Drug: Prednisolone; Drug: Hydrocortisone

Interventions

Prednisolone DRUG

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

Hydrocortisone first; prednisolone second; Prednisolone first; hydrocortisone second

Hydrocortisone DRUG

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

Hydrocortisone first; prednisolone second; Prednisolone first; hydrocortisone second

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead
• National Institute for Health Research, United Kingdom: collaborator
• Imperial Health Charity: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 8RF, United Kingdom

Location

MeSH Terms

Conditions

Adrenal Insufficiency

Interventions

Prednisolone; Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Karim Meeran, MBBS BSc MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm, two-period, double-blind randomised crossover study

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 3, 2019
• Study Start: July 31, 2019
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)