CORE: Bioequivalence Study of Prednisolone and Dexamethasone

Sponsor
University Medical Center Groningen (Other)
Overall Status
Recruiting
CT.gov ID
NCT04733144
Collaborator
(none)
24
1
2
14.9
1.6

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
An Bioequivalence Study of Prednisolone and Dexamethasone; Corticosteroids Revised - The CORE Study
Actual Study Start Date :
Mar 4, 2021
Anticipated Primary Completion Date :
May 31, 2022
Anticipated Study Completion Date :
May 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Prednisolone-Dexamethasone

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

Drug: Dexamethasone
1,125 mg dexamethasone 4,5 mg dexamethasone

Active Comparator: Dexamethasone-Prednisolone

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

Drug: Dexamethasone
1,125 mg dexamethasone 4,5 mg dexamethasone

Outcome Measures

Primary Outcome Measures

  1. Suppression of the hypothalamic-pituitary-adrenal axis - low dose [1 week per treatment]

    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

  2. Suppression of the hypothalamic-pituitary-adrenal axis - high dose [1 week per treatment]

    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)

Secondary Outcome Measures

  1. Changes in hypothalamic-pituitary-adrenal axis suppression - 1 [1 week per treatment]

    Effect of a dosage increase from low dose to high dose prednisolone on total urinary cortisol excretion in 24h-urine

  2. Changes in hypothalamic-pituitary-adrenal axis suppression - 2 [1 week per treatment]

    Effect of a dosage increase from low dose to high dose dexamethasone on total urinary cortisol excretion in 24h-urine

  3. Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol [1 week per treatment]

    The between-group difference in plasma cortisol levels

  4. Suppression of the hypothalamic-pituitary-adrenal axis - ACTH [1 week per treatment]

    The between-group difference in adrenocorticotropic hormone levels

  5. Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile [1 week per treatment]

    The between-group difference in metabolites of the 24h-urine steroid profile

  6. Suppression of the hypothalamic-pituitary-gonadal axis - androgen profile [1 week per treatment]

    The between-group difference in androgen profiles

  7. Suppression of the hypothalamic-pituitary-gonadal axis - gonadotropins [1 week per treatment]

    The between-group difference in luteinizing hormone and follicle stimulating hormone

  8. Suppression of the hypothalamic-pituitary-gonadal axis - metabolites of the 24h-urine steroid profile [1 week per treatment]

    The between-group difference in metabolites of the 24h-urine steroid profile

  9. Pharmacokinetics [1 week per treatment]

    Area under the curve

  10. Suppression of the immune system - granulocyte count [1 week per treatment]

    The between-group difference in granulocyte count

  11. Suppression of the immune system - PBMCs [1 week per treatment]

    The between-group difference in peripheral blood mononuclear cell count

  12. Effect on blood pressure [1 week per treatment]

    The between-group difference in systolic and diastolic blood pressure

  13. Effect on the Renin-angiotensin-aldosterone system - plasma renin [1 week per treatment]

    The between-group difference in plasma renin

  14. Effect on the Renin-angiotensin-aldosterone system - aldosterone [1 week per treatment]

    The between-group difference in aldosterone

  15. Effect on the Renin-angiotensin-aldosterone system - plasma potassium [1 week per treatment]

    The between-group difference in plasma potassium

  16. Effect on the Renin-angiotensin-aldosterone system - 24h-urine potassium [1 week per treatment]

    The between-group difference in 24h-urine potassium

  17. Effect on the Renin-angiotensin-aldosterone system - trans-tubular potassium gradient [1 week per treatment]

    The between-group difference in trans-tubular potassium gradient

  18. Metabolic parameters - OGTT [1 week per treatment]

    The between-group difference in oral glucose tolerence tests

  19. Metabolic parameters - lipid profile [1 week per treatment]

    The between-group difference in lipid profile

  20. Metabolic parameters - NEFAs [1 week per treatment]

    The between-group difference in non-esterified fatty acids

  21. Muscle mass [1 week per treatment]

    The between-group difference in 24h urinary creatinine excretion rate

  22. Muscle strength [1 week per treatment]

    The between-group difference in handgrip strength

  23. Clinical parameters - Weight [1 week per treatment]

    The between-group difference in weight in kg

  24. Clinical parameters - Body Mass Index (BMI) [1 week per treatment]

    The between-group difference in BMI in kg/m2

  25. Clinical parameters - Waist circumference [1 week per treatment]

    The between-group difference in waist circumference in cm

  26. Clinical parameters - Hip circumference [1 week per treatment]

    The between-group difference in hip circumference in cm

  27. Questionnaires - Quality of life [1 week per treatment]

    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.

  28. (Serious) Adverse Events [1 week per treatment]

    The between-group difference in (serious) adverce events

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University Medical Center Groningen Groningen Netherlands 9713 GZ

Sponsors and Collaborators

  • University Medical Center Groningen

Investigators

  • Principal Investigator: André P. van Beek, MD,PhD, University Medical Center Groningen
  • Principal Investigator: Stephan J.L. Bakker, MD,PhD, University Medical Center Groningen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
A.P. van Beek, MD PhD, Dr. A.P. van Beek, Endocrinologist, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier:
NCT04733144
Other Study ID Numbers:
  • 201900874
  • 2019-004983-23
First Posted:
Feb 1, 2021
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 12, 2022