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

December 15, 2021 updated by: University of Sao Paulo General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403-000
        • Hospital das Clínicas da Faculdade de Medicina da USP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 64 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: 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 100 mg/day
Other Names:
  • Thalidomide 100 mg
ACTIVE_COMPARATOR: Inactive SLE with standard dose of HCQ
This subproject includes one arm of lupus patients with inactive disease, in which will be maintained on standard dose of Hydroxychloroquine (400mg/day).
Drug: standard dose of HCQ
Hydroxychloroquine 5.0 mg/kg/day
Other Names:
  • HCQ standard
ACTIVE_COMPARATOR: Inactive SLE with reduced dose of HCQ
This subproject includes one arm of lupus patients with inactive disease: in which the dose will be reduced to 400mg 3 times a week (Hydroxychloroquine reduced).
Drug: Hydroxychloroquine reduced
Hydroxychloroquine 2.5 mg/kg/day
Other Names:
  • HCQ reduced

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Levels of Thalidomide
Time Frame: 12 months
Serum levels of thalidomide by liquid chromatography and tandem mass spectrometry (HPLC-MS/MS)
12 months
Serum Levels of Hydroxycloroquine
Time Frame: 12 months
Serum levels of hydroxycloroquine by LCMS
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

  • Principal Investigator: Eloisa Bonfa, MD, PhD, University of Sao Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 5, 2017

Primary Completion (ACTUAL)

December 30, 2020

Study Completion (ACTUAL)

March 30, 2021

Study Registration Dates

First Submitted

April 17, 2017

First Submitted That Met QC Criteria

April 17, 2017

First Posted (ACTUAL)

April 20, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 16, 2021

Last Update Submitted That Met QC Criteria

December 15, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HPLC-Rheumatic diseases

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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