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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002050-36 | EudraCT Number |
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| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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This research study is a multicentre prospective pharmacokinetic study. The clinical and biological data will be collected in the framework of a prospective study. The drug to be evaluated is a glucocorticoid routinely used to treat Systemic lupus erythematosus (SLE) patient. Initial dose of prednisone must be oral and at least 0.5mg/Kg/day, but the precise dosage and the tapering regimen will be determined according to the clinical judgment of the investigator. The duration of the research period for each patient will be 3 months. Three visits (which are all usual care visits) will be needed within the 3 months of the study for collecting data and/or blood sampling
Until now, glucocorticoids always play a leading role in the lupus treatment, and the lupus's prognosis has been greatly improved by the treatment of serious flare-ups with a combination of high-dose corticosteroids and immunosuppressants, notably mycophenolate mofetil (MMF) together with hydroxychloroquine (Plaquenil), survival at 10 years being 70 to 90%. However, corticosteroid treatment is also a major cause of morbidity and mortality, and with 60 years of experience, consensus about "appropriate" dosages, route of administration and tapering regimes has not been reached. In addition, there is a large variability in clinical response to corticosteroid therapy which may be attributed to heterogeneity of SLE, drugs interaction or to environmental and genetic factors, especially to polymorphism of the MDR (multi-drug resistance) -1 and NR3C1 (glucocorticoid nuclear receptor subfamily 3, group C, member 1). There are no previous studies investigating the role of MDR-1 and NR3C1 genes polymorphisms in the response to corticosteroids in lupus patients Drug monitoring of immunosuppressive drugs has been largely explored in renal transplantation and in a lesser extend in SLE (especially for mycophenolic acid). Relationship between prednisolone PK and clinical efficacy/toxicity have been also shown previously especially in renal transplant population. In patients with SLE, only two small series (8 children, 25 adults) have explored this relationship, and suggested that SLE activity and corticosteroid toxicity might be related to prednisolone AUC. Thus, limited data suggest that prednisone monitoring may optimize treatment efficacy and minimize adverse events.
The DECOR study will aim :
This approach could be applied to all inflammatory diseases requiring prolonged corticosteroid treatment, and thus, be a major progress in the use of this old treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pharmacokinetics/dynamics | Experimental | Blood samples at 3 visits |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood samples | Other | Blood samples at 3 visits : V0 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis V1 : - 5 mL in heparin tube / sample (2 to 5 samples) Pharmacokinetics + Pharmacogenetics + Gene Expression Analysis V2 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis and - 5 mL in EDTA tube / DNA bank |
| Measure | Description | Time Frame |
|---|---|---|
| SELENA-SLEDAI score | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Primary parameters : volume of distribution | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Primary parameters : elimination clearance |
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Inclusion Criteria:
Patient aged ≥ 6 years
Patient who met the American College of Rheumatology criteria (ACR) or the Systemic Lupus International Collaborating Clinics Classification (SLICC) for systemic lupus erythematosus.
Patients needs (re)initiation of oral prednisone regimen at least at 0.5 mg/Kg/d(or >30mg/d for patients >60 kg) in combination with mycophenolate mofetyl or mycofenolic acid or cyclophosphamide at usual dose including :
i) patient who receives bolus of methylprednisolone the week before and/or the week after inclusion for treating the lupus flare ii) patient who was previously treated by a low-prednisone dose (≤ 7.5 mg/d in patients ≥ 60 kg and ≤ 0.1 mg/kd/d in patient < 60 kg).
iii) patient who was previously treated by prednisone ≥ 0,5 mg/kg/d (or >30mg/d for patients >60 kg) but stopped since at least one month before inclusion
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michaela SEMERARO | Assistance Publique - Hôpitaux de Paris | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Necker Enfants Malades | Paris | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15634032 | Background | Czock D, Keller F, Rasche FM, Haussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. | |
| 21982386 | Background | Sagcal-Gironella AC, Sherwin CM, Tirona RG, Rieder MJ, Brunner HI, Vinks AA. Pharmacokinetics of prednisolone at steady state in young patients with systemic lupus erythematosus on prednisone therapy: an open-label, single-dose study. Clin Ther. 2011 Oct;33(10):1524-36. doi: 10.1016/j.clinthera.2011.09.015. Epub 2011 Oct 7. |
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| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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|
To study the pharmacokinetics of prednisolone in a population of patients with SLE
| Day 0, 1 month, 3 months |
| Primary parameters : absorption constant | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Secondary parameters : trough concentration | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Secondary parameters : maximum concentration | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Secondary parameters : Area Under Curve (AUC) | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Secondary parameters : elimination half-life | To study the pharmacokinetics of prednisolone in a population of patients with SLE | Day 0, 1 month, 3 months |
| Occurrence of adverse events | 3 months |
| 18165172 | Background | Piotrowski P, Burzynski M, Lianeri M, Mostowska M, Wudarski M, Chwalinska-Sadowska H, Jagodzinski PP. Glucocorticoid receptor beta splice variant expression in patients with high and low activity of systemic lupus erythematosus. Folia Histochem Cytobiol. 2007;45(4):339-42. |
| 19594946 | Background | Du J, Li M, Zhang D, Zhu X, Zhang W, Gu W, Feng Y, Zhai X, Ling C. Flow cytometry analysis of glucocorticoid receptor expression and binding in steroid-sensitive and steroid-resistant patients with systemic lupus erythematosus. Arthritis Res Ther. 2009;11(4):R108. doi: 10.1186/ar2763. Epub 2009 Jul 14. |
| 17630118 | Background | Stahn C, Lowenberg M, Hommes DW, Buttgereit F. Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol. 2007 Sep 15;275(1-2):71-8. doi: 10.1016/j.mce.2007.05.019. Epub 2007 Jun 2. |
| 18321483 | Background | Derijk RH, de Kloet ER. Corticosteroid receptor polymorphisms: determinants of vulnerability and resilience. Eur J Pharmacol. 2008 Apr 7;583(2-3):303-11. doi: 10.1016/j.ejphar.2007.11.072. Epub 2008 Jan 30. |
| 20712049 | Background | Mwinyi J, Wenger C, Eloranta JJ, Kullak-Ublick GA. Glucocorticoid receptor gene haplotype structure and steroid therapy outcome in IBD patients. World J Gastroenterol. 2010 Aug 21;16(31):3888-96. doi: 10.3748/wjg.v16.i31.3888. |
| 19818358 | Background | Nicolaides NC, Galata Z, Kino T, Chrousos GP, Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids. 2010 Jan;75(1):1-12. doi: 10.1016/j.steroids.2009.09.002. Epub 2009 Oct 7. |
| 21164266 | Background | van Rossum EFC, van den Akker ELT. Glucocorticoid resistance. Endocr Dev. 2011;20:127-136. doi: 10.1159/000321234. Epub 2010 Dec 16. |
| 23873876 | Background | Duru N, van der Goes MC, Jacobs JW, Andrews T, Boers M, Buttgereit F, Caeyers N, Cutolo M, Halliday S, Da Silva JA, Kirwan JR, Ray D, Rovensky J, Severijns G, Westhovens R, Bijlsma JW. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2013 Dec;72(12):1905-13. doi: 10.1136/annrheumdis-2013-203249. Epub 2013 Jul 19. |
| 23232124 | Background | Luijten RK, Fritsch-Stork RD, Bijlsma JW, Derksen RH. The use of glucocorticoids in systemic lupus erythematosus. After 60 years still more an art than science. Autoimmun Rev. 2013 Mar;12(5):617-28. doi: 10.1016/j.autrev.2012.12.001. Epub 2012 Dec 8. |
| 23888367 | Background | Fangtham M, Petri M. 2013 update: Hopkins lupus cohort. Curr Rheumatol Rep. 2013 Sep;15(9):360. doi: 10.1007/s11926-013-0360-0. |
| 10943870 | Background | Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000 Aug;43(8):1801-8. doi: 10.1002/1529-0131(200008)43:83.0.CO;2-O. |
| 25861455 | Background | Al Sawah S, Zhang X, Zhu B, Magder LS, Foster SA, Iikuni N, Petri M. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus-the Hopkins Lupus Cohort. Lupus Sci Med. 2015 Mar 11;2(1):e000066. doi: 10.1136/lupus-2014-000066. eCollection 2015. |
| 40411119 | Result | Bouazza N, Semeraro M, Lui G, Froelicher-Bournaud L, Choupeaux L, Treluyer JM, Benaboud S, Terzic J, Hachulla E, Remy P, Harambat J, Karras A, Rousset-Rouviere C, Jolivot A, Amoura Z, Daugas E, Hummel A, Salomon R, Lega JC, Decramer S, Belot A, Gobert D, Costedoat-Chalumeau N, Faguer S, Melki I, Jourde-Chiche N, Bader-Meunier B. Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity. Br J Clin Pharmacol. 2025 Oct;91(10):2854-2864. doi: 10.1002/bcp.70103. Epub 2025 May 23. |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |