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Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone (DECOR)

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ClinicalTrials.gov Identifier: NCT03187743
Recruitment Status : Recruiting
First Posted : June 15, 2017
Last Update Posted : August 13, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Lupus Erythematosus, Systemic Other: Blood samples Not Applicable

Detailed Description:

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 :

  1. to search for relationship between prednisolone PK and SLE disease activity in a large series of patients in order to improve the rational of prednisone doses in lupus patients
  2. to identify pharmacogenetic factors influencing the response to steroid in order to identify patients sharing a high probability of being responders or resistant to corticosteroids.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalised Pharmacological Approach to the Tapering of Corticosteroid Doses in Systemic Lupus Patients Treated With Prednisone
Actual Study Start Date : April 17, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus Steroids
Drug Information available for: Prednisone

Arm Intervention/treatment
Experimental: Pharmacokinetics/dynamics
Blood samples at 3 visits
Other: Blood samples

Blood samples at 3 visits :

V0 : - 5 mL in heparin tube / Pharmacokinetics + Gene Expression Analysis only if previous treatment with low-dose prednisone

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





Primary Outcome Measures :
  1. SELENA-SLEDAI score [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Primary parameters : volume of distribution [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  2. Primary parameters : elimination clearance [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  3. Primary parameters : absorption constant [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  4. Secondary parameters : trough concentration [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  5. Secondary parameters : maximum concentration [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  6. Secondary parameters : Area Under Curve (AUC) [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  7. Secondary parameters : elimination half-life [ Time Frame: Day 0, 1 month, 3 months ]
    To study the pharmacokinetics of prednisolone in a population of patients with SLE

  8. Occurrence of adverse events [ Time Frame: 3 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  • Patient with stable doses of other immunosuppressive or biological drugs before inclusion (at least 15 days for Imurel, Methotrexate, Tacrolimus ; at least 6 months for Rituximab, Belimumab) and during the 3 months of patient participation in the study.
  • Signed informed consent form by the patient (if aged ≥ 18 years), or by the parents / legal guardian and patient's agreement (if aged < 18 years)
  • Patient affiliated to the health insurance system

Exclusion Criteria:

  • Patient presents contraindications to corticosteroids and/or MMF, mycofenolic acid or cyclophosphamide
  • Patient cannot be treated by oral way
  • Patient whose physician has planned to stop prednisone in less than 3 months
  • Patient (or parents for minor) are unable to give a written informed consent for physical or psychical reasons
  • Patient disagrees with the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03187743


Contacts
Contact: Brigitte BADER-MEUNIER, MD, PhD +33 (0) 1 44 49 43 32 brigitte.bader-meunier@aphp.fr
Contact: Elodie HENRY, Master +33 1 44 49 56 66 elodie.henry@aphp.fr

Locations
France
Hospital Necker Enfants Malades Recruiting
Paris, France, 75015
Contact: Brigitte BADER-MEUNIER, MD, PhD    +33 (0) 1 44 49 43 32    brigitte.bader-meunier@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Director: Michaela SEMERARO Assistance Publique - Hôpitaux de Paris

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03187743     History of Changes
Other Study ID Numbers: P160935J
2017-002050-36 ( EudraCT Number )
First Posted: June 15, 2017    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Lupus erythematosus
Systemic
Corticosteroid
Prednisone
Pharmacokinetics

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents