Evaluation of High Dose Prednisolone Pharmacokinetics in the Acute and Chronic Setting

NCT ID: NCT05012033

Last Updated: 2023-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-04-12

Study Completion Date

2026-03-26

Brief Summary

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This is a pilot study to investigate serum prednisolone profiles in:

* Patients on high doses of prednisolone for any inflammatory disorder, both in the acute and chronic setting.
* Patients stepping up from or down to prednisolone therapy in association with a course of high dose methyl-prednisolone or dexamethasone.

The study will comprise 3 groups, including those started on high doses of prednisolone acutely in an inpatient or outpatient setting, participants on chronically high doses, and those receiving a several week course of high dose methylprednisolone or dexamethasone.

The study aims to measure prednisolone levels at a number of time points to investigate serum profile differences in those receiving prednisolone acutely compared with longer term steroid use. Further samples will be taken to characterise additional metabolic changes.

Detailed Description

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Prednisolone is an anti-inflammatory drug widely used to reduce inflammation and immune activation in a number of medical conditions, including asthma, allergy, inflammatory and auto-immune conditions. Its therapeutic actions, however, are accompanied by several adverse side effects, which are more frequent following high doses and long term treatments. The aim is therefore to use the lowest effective dose or highest dose for the shortest treatment required.

It has been observed in a select number of patients on replacement prednisolone doses for adrenal insufficiency (AI) that serum prednisolone levels change over time, despite patients remaining on the same dose. It is currently unclear whether serum levels of prednisolone match the doses in patients taking high dose prednisolone, both in the acute and chronic setting, and whether the way in which prednisolone is metabolised is altered after receiving high doses for prolonged periods of time.

The rationale for the use of particular doses for particular conditions is not clear, and has been developed historically in the absence of individual patient data. It is possible that more tailored dosing of prednisolone will result in reduced side effects, and that the minimum possible dose may be weight related.

In addition, genetic and epigenetic factors may also play a role in the efficacy of prednisolone and in the risk of developing side effects, accounting for some of the inter-individual variation in drug response.

Further characterising this may help to create an evidence base to tailor anti-inflammatory doses and weaning regimens of synthetic glucocorticoids that avoid deleterious effects.

Conditions

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Thyroid Eye Disease Vasculitis COPD Exacerbation Acute Asthma Inflammatory Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Group A

Patients started acutely on high dose prednisolone (\>30mg for any inflammatory condition)

No intervention - prednisolone is taken as part if routine clinical care.

Intervention Type OTHER

Prednisolone given orally prior to taking timed samples for levels

Group B

Patients on longer term anti-inflammatory doses of prednisolone to treat any medical condition warranting their use, including post COVID.

No intervention - prednisolone is taken as part if routine clinical care.

Intervention Type OTHER

Prednisolone given orally prior to taking timed samples for levels

Group C

Patients receiving multiple high doses of methylprednisolone or dexamethasone in association with oral prednisolone.

No intervention - prednisolone is taken as part if routine clinical care.

Intervention Type OTHER

Prednisolone given orally prior to taking timed samples for levels

Interventions

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No intervention - prednisolone is taken as part if routine clinical care.

Prednisolone given orally prior to taking timed samples for levels

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Aged 18 - 75 years
* Male or female
* Participants who are otherwise healthy enough to participate, as determined by pre-study medical history
* Participants who are able and willing to give written informed consent to participate in the study
* Group A only: Patients requiring acute (\<5 days) high dose (minimum 30mg) oral prednisolone therapy for antiinflammatory purposes in either an inpatient or outpatient setting.
* Group B only: Minimum of 1 month duration of high dose prednisolone (\>30mg) if in the chronic use group.
* Group C only: Patients started on high dose methylprednisolone (\>3 day course) or prolonged courses of dexamethasone.

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, aminogluethimide, itraconazole, ketoconazole, ciclosporin or ritonavir.
* Pregnancy. Females of child-bearing age will be asked to provide a urine sample for a pregnancy test at each visit.
* History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karim Meeran, MBBS BSc MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Katharine Lazarus, MBChB MRCP

Role: CONTACT

07555717544

Other Identifiers

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21HH6792

Identifier Type: -

Identifier Source: org_study_id

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