Bioequivalence Study of Prednisolone and Dexamethasone

Healthy Volunteers Clinical Trial

— CORE  

Official title:

An Bioequivalence Study of Prednisolone and Dexamethasone; Corticosteroids Revised - The CORE Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04733144
• Other study ID #: 201900874
• Secondary ID: 2019-004983-23
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2021
• Est. completion date: May 31, 2022

Study information

• Verified date: April 2022
• Source: University Medical Center Groningen
• Contact: Suzanne P. Stam, MD
• Phone: 0031503617293
• Email: s.p.stam[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study design: A randomised, double blind, cross-over clinical trial.

Study population: healthy human adult volunteers including 12 males and 12 females aged 18-75 years old.

Intervention: In random order, subjects will receive 7,5 mg prednisolone for one week, directly followed by 30 mg of prednisolone for one week. After a washout period of 4 weeks (or by exception 8 weeks), subjects will receive 1,125 mg dexamethasone for one week, directly followed by 4,5 mg dexamethasone for one week.

Main study parameters/endpoints: The main study endpoint is the difference in total urinary cortisol excretion as measured in 24h-urine between the lower doses of prednisolone and dexamethasone as well as between the higher doses of prednisolone and dexamethasone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: May 31, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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:

1. Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers

2. Diseases affecting the HPG-axis: e.g. Cushing disease.

3. Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma

4. Psychiatric diseases

5. 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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Prednisolone
7,5 mg prednisolone (low dose) 30 mg prednisolone (high dose)
• Dexamethasone
1,125 mg dexamethasone 4,5 mg dexamethasone

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Changes in hypothalamic-pituitary-adrenal axis suppression - 1	Effect of a dosage increase from low dose to high dose prednisolone on total urinary cortisol excretion in 24h-urine	1 week per treatment
Secondary	Changes in hypothalamic-pituitary-adrenal axis suppression - 2	Effect of a dosage increase from low dose to high dose dexamethasone on total urinary cortisol excretion in 24h-urine	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol	The between-group difference in plasma cortisol levels	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-adrenal axis - ACTH	The between-group difference in adrenocorticotropic hormone levels	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile	The between-group difference in metabolites of the 24h-urine steroid profile	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-gonadal axis - androgen profile	The between-group difference in androgen profiles	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-gonadal axis - gonadotropins	The between-group difference in luteinizing hormone and follicle stimulating hormone	1 week per treatment
Secondary	Suppression of the hypothalamic-pituitary-gonadal axis - metabolites of the 24h-urine steroid profile	The between-group difference in metabolites of the 24h-urine steroid profile	1 week per treatment
Secondary	Pharmacokinetics	Area under the curve	1 week per treatment
Secondary	Suppression of the immune system - granulocyte count	The between-group difference in granulocyte count	1 week per treatment
Secondary	Suppression of the immune system - PBMCs	The between-group difference in peripheral blood mononuclear cell count	1 week per treatment
Secondary	Effect on blood pressure	The between-group difference in systolic and diastolic blood pressure	1 week per treatment
Secondary	Effect on the Renin-angiotensin-aldosterone system - plasma renin	The between-group difference in plasma renin	1 week per treatment
Secondary	Effect on the Renin-angiotensin-aldosterone system - aldosterone	The between-group difference in aldosterone	1 week per treatment
Secondary	Effect on the Renin-angiotensin-aldosterone system - plasma potassium	The between-group difference in plasma potassium	1 week per treatment
Secondary	Effect on the Renin-angiotensin-aldosterone system - 24h-urine potassium	The between-group difference in 24h-urine potassium	1 week per treatment
Secondary	Effect on the Renin-angiotensin-aldosterone system - trans-tubular potassium gradient	The between-group difference in trans-tubular potassium gradient	1 week per treatment
Secondary	Metabolic parameters - OGTT	The between-group difference in oral glucose tolerence tests	1 week per treatment
Secondary	Metabolic parameters - lipid profile	The between-group difference in lipid profile	1 week per treatment
Secondary	Metabolic parameters - NEFAs	The between-group difference in non-esterified fatty acids	1 week per treatment
Secondary	Muscle mass	The between-group difference in 24h urinary creatinine excretion rate	1 week per treatment
Secondary	Muscle strength	The between-group difference in handgrip strength	1 week per treatment
Secondary	Clinical parameters - Weight	The between-group difference in weight in kg	1 week per treatment
Secondary	Clinical parameters - Body Mass Index (BMI)	The between-group difference in BMI in kg/m2	1 week per treatment
Secondary	Clinical parameters - Waist circumference	The between-group difference in waist circumference in cm	1 week per treatment
Secondary	Clinical parameters - Hip circumference	The between-group difference in hip circumference in cm	1 week per treatment
Secondary	Questionnaires - Quality of life	The between-group difference in quality of life, measured using the 36-Item Short Form Health Survey (SF-36). The score ranges from 0-100, with lower scores indicating a worse health status.	1 week per treatment
Secondary	(Serious) Adverse Events	The between-group difference in (serious) adverce events	1 week per treatment