Scrutinizing the Heterogeneity of SLE: Defining Phenotypes

November 17, 2017 updated by: Murray B Urowitz, MD FRCP(C), University Health Network, Toronto

Scrutinizing the Heterogeneity of Systemic Lupus Erythematosus: Defining Phenotypes

SLE disease course is characterized by unpredictable relapses and remissions in the majority of patients. However, in a small proportion (approximately 5%), SLE presents with a monophasic pattern, meaning that these patients have active disease before and immediately after diagnosis and after some time they achieve prolonged remission (for 12 years on average). Interestingly, about half of these patients do so and require no medications. On the other end of the clinical spectrum, approximately 50% of the patients demonstrate persistent disease activity and usually have the highest risk for developing co-morbidities and irreversible damage. A major goal of clinical research in SLE is to improve disease management based on disease course. By better characterizing SLE disease course we hope to better identify patients early in the disease course for targeted therapies to prevent and or reduce future SLE complications.

The overall objective of our project is to define distinct phenotypes of SLE based on disease course, clinical features, pathogenic mechanisms, genetic factors and relevant biomarkers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Specific aims of this study are:

  1. To test the clinical impression of the disease courses by modeling the course of the disease in each of three sub-populations of patients where it is anticipated that one sub-population will experience relapsing and remitting disease activity, one will experience persistently active disease and another will exhibit a monophasic pattern.
  2. To develop predictive models for group membership to enhance the accuracy of prognosis.
  3. To test these models in the inception cohort of SLE patients within the Toronto Lupus Cohort.

Study Design: Retrospective longitudinal observational cohort

Patients will be categorised into three disease courses:

I. Relapsing-remitting II. Persistently active III. Monophasic Relapsing/remitting is defined as periods of disease activity SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone) less than 50% of the time alternating with periods of inactivity (SLEDAI-2K <4) over the course of follow-up.

Persistently active disease is defined as SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone), in greater than 80% of the visits, or no 2 consecutive visits with SLEDAI-2K < 4.

Monophasic course is defined as disease activity SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone) for an initial period of less than 3 years followed by resolution and inactive disease (SLEDAI-2K of 0 excluding serology) for at least 5 years.

Clinical and laboratory characteristics, therapies and outcomes for each subgroup will be described. Identification of all clinical and laboratory features of lupus contained in the CRF will be compared for each group, as well as the medications prescribed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
950

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T2S8
        • University Health Network

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Patients with SLE have been followed prospectively at the University of Toronto Lupus Clinic since 1970. All patients ≥4 or more of the 1997 ACR criteria for SLE, or have 3 criteria and a typical lesion of SLE on renal or skin biopsy. Patients are evaluated at 2-6 month intervals according to a standard protocol which includes a detailed clinical history, physical examination, and laboratory evaluation . It includes all information necessary to calculate disease activity and damage indices, as well as comorbidities. Disease activity is assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) , and accumulated damage by the SLICC/ACR damage index (SDI) .

To date there are 1767 patients with 2 or more visits registered in the Lupus Clinic Database, with 43079 assessments recorded. Their characteristics are shown in Table 1.

Description

Inclusion Criteria:

Patients enrolled in the study for aims 1 and 2 must meet the following inclusion criteria:

  1. ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy.
  2. Patients must have a minimum of 2 assessment visits.

Patients enrolled in the study for aim 3 must meet the following criteria:

  1. Must be inception patients seen within one year of diagnosis of SLE
  2. ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy.
  3. Patients must have a minimum of 6 assessment visits to ensure categorization into one of the disease courses derived in aims 1 and 2

Exclusion Criteria:

  1. Patients who have not had 2 assessment visits for aims 1 and 2
  2. Patients who have not had 6 assessments for aim 3.

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Disease Course Patterns
Time Frame: 6 months
All 49,000 visits within the Toronto Lupus Cohort will be probed for patterns of disease activity using SLEDAI-2K measurements on each assessment. A finite mixture model will be fitted to the data to accommodate for three sub-populations of patients. Disease course for each sub-populations will be defined in terms of multistate model where the states reflected meaningfully different degrees of disease activity as measured by the SLEDAI-2K scores.
6 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Murray Urowitz, University Health Network and University of Toronto

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 9, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 30, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-5083

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No IPD data will be shared with other researchers

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.

Clinical Trials on Systemic Lupus Erythematosus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings