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

NCT05012033 | Recruiting DMC

• 1 other identifier: 21HH6792
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Thyroid Eye Disease; Vasculitis; COPD Exacerbation Acute; Asthma; Inflammatory Disease

Outcome Measures

Primary Outcomes (4)

• To elucidate differences in prednisolone pharmacokinetics (in patients receiving high dose prednisolone acutely and in the chronic setting).

  This will be assessed by determination of Cmax

  Pharmacokinetics measurements taken at the first and second visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

• To elucidate differences in prednisolone pharmacokinetics (in patients receiving high dose

  This will be assessed by determination of Tmax

  Pharmacokinetics measurements taken at the first and second visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

• To elucidate differences in prednisolone pharmacokinetics (in patients receiving high dose

  This will be assessed by determination of prednisolone half life and area under the curve values.

  Pharmacokinetics measurements taken at the first and second visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

• To elucidate differences in prednisolone pharmacokinetics (in patients receiving high dose

  This will be assessed by determination of urinary steroid profiles.

  Pharmacokinetics measurements taken at the first and second visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

Secondary Outcomes (6)

• To elucidate further differences in metabolic profiles and glucocorticoid axis

  Time points post prednisolone dose at 1st and 2nd visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

• Exploratory Outcomes

  Time points post prednisolone dose at 1st and 2nd visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

• Surrogate markers and risk factors for cardiovascular disease

  On 1st and 2nd visits

• Surrogate markers and risk factors for cardiovascular disease

  On 1st and 2nd visits

• Surrogate markers and risk factors for cardiovascular disease

  On 1st and 2nd visits. This will be of variable duration depending on duration of steroid treatment (5 days up to 2 years)

Study Arms (3)

Group A

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

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

Group B

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

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

Group C

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

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

Interventions

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

Prednisolone given orally prior to taking timed samples for levels

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients receiving high dose prednisolone for any inflammatory disorder.

You may qualify if:

• 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.

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, 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.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Graves Ophthalmopathy; Vasculitis; Asthma

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity

Study Officials

• Karim Meeran, MBBS BSc MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katharine Lazarus, MBChB MRCP

CONTACT

07555717544; imperial.steroids@nhs.net

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 19, 2021
• Study Start: April 12, 2023
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)