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Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases

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ClinicalTrials.gov Identifier: NCT03122431
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : April 19, 2018
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
University of Sao Paulo General Hospital

Brief Summary:
No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus (SLE) Juvenile SLE Cutaneous Lupus Drug: Thalidomide Drug: Hydroxychloroquine reduced Drug: Hydroxychloroquine high Phase 4

Detailed Description:
No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. There is also a large inter-individual variability in response to treatments with regard to efficacy and toxicity, and for many drugs, there is also a period of weeks to months to establish its efficacy. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. The implementation of this methodology dedicated to research in our center, with the necessary training of human resources, will enable the standardization and availability of this advanced technology to other muldisciplinary projects in various areas of science. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This thematic project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study includes 3 subprojects that will assess serum drug levels for efficacy and toxicity. In the first two subprojects, hydroxychloroquine will be studied in SLE population. In the third subproject, thalidomide and SLE and cutaneous lupus will be studied.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Relevance of Monitoring Blood Levels Compared to Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases: Adherence and Understanding the Possible Underlying Mechanisms Involved in Effectiveness and in Adverse Effects
Actual Study Start Date : June 5, 2017
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 5, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
SLE/cutaneous lupus with thalidomide
This subproject includes only one arm of lupus patients with active and refractory cutaneous disease and eligible for Thalidomide 100mg/day for 12 months.
Drug: Thalidomide
Thalidomide 100mg/day
Other Name: Thalidomide 100 MG

No Intervention: Inactive SLE with standard dose of HCQ
This subproject includes 2 arms of lupus patients with inactive disease: one group will be maintained on standard dose of Hydroxychloroquine (400mg/day) and in the other, the dose will be reduced to 400mg 3 times a week for two years.
Active Comparator: Inactive SLE with reduced dose of HCQ
This subproject includes 2 arms of lupus patients with inactive disease: one group will be maintained on standard dose of Hydroxychloroquine (400mg/day) for two years and in the other, the dose will be reduced to 400mg 3 times a week (Hydroxychloroquine reduced) for two years.
Drug: Hydroxychloroquine reduced
Hydroxychloroquine 400mg three times a week
Other Name: HCQ reduced

Experimental: Active SLE with initial high dose of HCQ
This subproject includes 2 arms of lupus patients with active disease: one group will be started on standard dose of Hydroxychloroquine (400mg/day) for two years and in the other, the dose will be started at high dose 800mg/day (Hydroxychloroquine high) for three months.
Drug: Hydroxychloroquine high
Hydroxychloroquine 800mg/day for three months
Other Name: HCQ high

No Intervention: Active SLE with standard dose of HCQ
This subproject includes 2 arms of lupus patients with active disease: one group will be started on standard dose of Hydroxychloroquine (400mg/day) for three months and in the other, the dose will be started at high dose 800mg/day (Hydroxychloroquine high) for three months.



Primary Outcome Measures :
  1. Serum levels of thalidomide [ Time Frame: 30 days, 3 months, 6 months and 12 months ]
    Improvement of Cutaneous Lupus Area and Severity Activity Index Score (CLASI)

  2. Serum levels of hydroxycloroquine - HCQ reduced [ Time Frame: 6 months, 12 months and 24 months ]
    Disease flare evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)

  3. Serum levels of hydroxycloroquine - HCQ high [ Time Frame: 3 months ]
    Disease flare evaluated by Systemic Lupus Erythematosus Disease Activity Index



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Thalidomide subproject:

Inclusion Criteria:

  • SLE diagnosis according to 1997 ACR criteria
  • Active and refractory cutaneous lupus lesions
  • Male gender (using contraceptive barrier method) or confirmed infertility for female gender
  • Normal electroneuromyography at study entry

Exclusion Criteria:

  • Alcoholism
  • History of peripheral neuropathy
  • Previous history of thrombophilia or positive antiphospholipid antibodies
  • Renal and/or central nervous system and/or hematological activity

HCQ reduced subproject:

Inclusion Criteria:

  • SLE diagnosis according to 1997 ACR criteria
  • Use of hydroxychloroquine (5 to 6.5mg/kg/day) for ≥5 years
  • SLEDAI-2K <4

Exclusion Criteria:

  • Alcoholism
  • Renal dialysis
  • Concomitant infectious process
  • Acute and chronic liver diseases
  • Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
  • Signs of Retinopathy

HCQ high subproject:

Inclusion Criteria:

  • SLE diagnosis according to 1997 ACR criteria
  • No use of hydroxychloroquine for ≥ 6 months
  • LES/LESJ in activity (SLEDAI≥6)

Exclusion Criteria:

  • Alcoholism
  • Renal dialysis
  • Concomitant infectious process
  • Acute and chronic liver diseases
  • Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
  • Signs of Retinopathy

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): NCT03122431


Contacts
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Contact: Eloisa Bonfa, MD, PhD 55 11 30617490 eloisa.bonfa@hc.fm.usp.br
Contact: Clovis Silva, MD, PhD 55 11 26618563 clovisaasilva@gmail.com

Locations
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Brazil
Hospital das Clinicas da Faculdade de Medicina da USP Recruiting
São Paulo, Brazil, 05403-000
Contact: Sandra G Pasoto, M.D., PhD.    30617490    sandra.pasoto@hc.fm.usp.br   
Contact: Nadia E Aikawa, M.D., PhD.    30617490    nadia.aikawa@hc.fm.usp.br   
Sponsors and Collaborators
University of Sao Paulo General Hospital
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
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Principal Investigator: Eloisa Bonfa, MD, PhD University of Sao Paulo

Publications:

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Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT03122431     History of Changes
Other Study ID Numbers: HPLC-Rheumatic diseases
First Posted: April 20, 2017    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Thalidomide
Hydroxychloroquine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents