Bioequivalence Study of Prednisolone and Dexamethasone

NCT04733144 | Unknown Phase 1

• 2 other identifiers: 2019008742019-004983-23
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare two different glucocorticoids, prednisolone and dexamethasone at two different doses for their organ specific effects, utilizing modern day standards.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Suppression of the hypothalamic-pituitary-adrenal axis - low dose

  Difference in HPA-axis suppression as measured by the difference of total urinary cortisol excretion in 24h-urine between 7,5 mg prednisolone and 1,125 mg dexamethasone

  1 week per treatment

• Suppression of the hypothalamic-pituitary-adrenal axis - high dose

  Difference of total urinary cortisol excretion in 24h-urine between 30 mg prednisolone (preceded by 7,5 mg prednisolone for one week) and 4,5 mg dexamethasone (preceded by 1,125 mg dexamethasone for one week)

  1 week per treatment

Secondary Outcomes (28)

• Changes in hypothalamic-pituitary-adrenal axis suppression - 1

  1 week per treatment

• Changes in hypothalamic-pituitary-adrenal axis suppression - 2

  1 week per treatment

• Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol

  1 week per treatment

• Suppression of the hypothalamic-pituitary-adrenal axis - ACTH

  1 week per treatment

• Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile

  1 week per treatment

Study Arms (2)

Prednisolone-Dexamethasone

ACTIVE COMPARATOR

Participants will receive 1 week of low dose (7,5 mg) prednisolone directly followed by 1 week of high dose prednisolone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose dexamethasone (1,125 mg) directly followed by 1 week of high dose dexamethasone (4,5 mg).

Drug: Prednisolone; Drug: Dexamethasone

Dexamethasone-Prednisolone

ACTIVE COMPARATOR

Participants will receive 1 week of low dose (1,125 mg) dexamethasone directly followed by 1 week of high dose dexamethasone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose prednisolone (7,5 mg) directly followed by 1 week of high dose prednisolone (30 mg).

Drug: Prednisolone; Drug: Dexamethasone

Interventions

Prednisolone DRUG

7,5 mg prednisolone (low dose) 30 mg prednisolone (high dose)

Dexamethasone-Prednisolone; Prednisolone-Dexamethasone

Dexamethasone DRUG

1,125 mg dexamethasone 4,5 mg dexamethasone

Dexamethasone-Prednisolone; Prednisolone-Dexamethasone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be healthy with no relevant medical history and no use of medication.
• Female participants aged \<50 years must be using oral contraceptives and female participants age ≥50 years must be in the postmenopausal state
• Command of the Dutch language
• Providing written IC
• BMI between 18.5 and 30 kg/m2
• Participants must be between 18 and 75 years of age

You may not qualify if:

• Potential participants who are unlikely to adhere to the study protocol (for instance subjects which have a history of substance abuse or non-compliance)
• Potential participants with a medical history of:
• Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers
• Diseases affecting the HPG-axis: e.g. Cushing disease.
• Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma
• Psychiatric diseases
• Diabetes
• Shift workers
• Potential participants with a kidney function \<60 ml/min/1.73m2, abnormalities in liver enzymes, and/or abnormalities in thyroid function
• Potential participants who are dependent on corticosteroids, e.g. asthmatic patients, and transplant recipients

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Related Publications (1)

• Stam SP, Vulto A, Vos MJ, Kerstens MN, Rutgers A, Kema I, Touw DJ, Bakker SJ, van Beek AP. Rationale and design of the CORE (COrticosteroids REvised) study: protocol. BMJ Open. 2022 Apr 26;12(4):e061678. doi: 10.1136/bmjopen-2022-061678.

  PMID: 35473729 DERIVED

MeSH Terms

Interventions

Prednisolone; Dexamethasone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• André P. van Beek, MD,PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Stephan J.L. Bakker, MD,PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suzanne P. Stam, MD

CONTACT

0031503617293; s.p.stam@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. A.P. van Beek, Endocrinologist, Principal Investigator

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: February 1, 2021
• Study Start: March 4, 2021
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: April 12, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 6 months and ending 10 years following article publication
• Access Criteria: Researchers should provide a methodologically sound proposal to a.p.van.beek@umcg.nl

Locations

NL (1)