The Impact of 6MP Metabolite Levels on Infliximab Pharmacokinetics and Anti-infliximab Antibodies in Crohn's Disease

February 14, 2017 updated by: Ernest Seidman
In this research proposal, the investigators will focus on methods to optimize the therapeutic response to anti-TNF antibodies, by determining a correlation of 6-mp metabolite levels with IFX trough levels, anti-IFX antibody levels and clinical response. The study will also evaluate (in vitro) the possible impact of vitamin D on the interaction of IFX with dendritic cells in both healthy subjects and patients with Crohn's disease (proliferation, maturation, cytokine profile, apoptosis, gene expression).

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite the evidence for the beneficial effects of thiopurine/IFX combined therapy on both the prevention of the development of anti-IFX antibodies (ATI) and improved clinical outcomes, no study has employed the proven clinical usefulness of measuring 6- MP metabolite levels. We hypothesize that targeting the established threshold of 6-TGN levels (between 235-400), shown to result in superior clinical efficacy, would reduce the development of ATI and enhance trough IFX levels. It is also conceivable that excessive6TGN levels may increase the risk of adverse events such as infections and neoplasms such as lymphomas, the major drawbacks to combination therapy. If a significant correlation between 6-TGN levels and diminished risk of ATI development or higher trough serum IFX levels can be demonstrated, it will allow for an improved approach towards pharmacological monitoring of these patients with optimization of the long term response of CD patients on anti-TNF therapy.

Vitamin D possesses profound immunomodulatory effects, mediated primarily through the innate immune system. Low serum levels of vitamin D are associated with worse outcomes in CD. IFX was reported to have a significant impact on maturation and phenotype of dendritic cells (DC). Previous work from our laboratory demonstrated a significant effect of vitamin D on expression of NOD2 along with a profound effect onthe cytokine profile of DC exposed to PRR stimulation85. We hypothesize that vitamin Ddeficiency may be associated with a lower clinical response to anti-TNF therapy. IFX and vitamin D may have a synergistic effect in modulating the immune system in IBD via interactions through innate or adaptive mechanisms. We expect that vitamin D may enhance IFX-induced shift in the maturation pathway and cytokine profile of DC exposed to intestinal microbes through pattern recognition receptors (PRR). Demonstration of a synergistic effect of vitamin D with anti-TNF antibodies may have important clinical implications for the care of IBD patients, particularly in Canada where the prevalence of vitamin D deficiency is very high. Such an effect was demonstrated for lymphocytes but was never examined for the innate immune system, considered to have a profound role in the pathogenesis of CD. The data from this study may provide further justification for the need of monitoring vitamin D status in CD patients, and its supplementation as an additional therapeutic tool for optimizing response to anti-TNF in CD.

This is a prospective cross-sectional and longitudinal multicentre non-interventional study. The patients will be recruited at the following centers: McGill University Health Center, Mount Sinai Medical Centre, Toronto, Canada; University of Calgary, U Alberta, Edmonton. This study will recruit patients (18-70 yrs) with Crohn's disease who are starting treatment with infliximab or combo therapy of infliximab and azathiopurine. This study will look at therapeutic monitoring end points to evaluate the impact of drug level and antibodies on the clinical effectiveness of treatment (mono or combo therapy). .

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.
225

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3G 1A4
        • Recruiting
        • Montreal General Hospital
        • Contact:
        • Principal Investigator:
          • Ernest Seidman, MDCM

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

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with a diagnosis of CD ,age 18-70 years, who are treated with IFX (standard 5 mg/kg/q8 weeks maintenance dose) or IFX (standard maintenance dose)/thiopurine (stable dose for at least 3 months) combination for <12 months.

Description

Inclusion Criteria:

  • Patients with a diagnosis of CD ,
  • age 18-70 years,
  • who are treated with IFX (standard 5 mg/kg/q8 weeks maintenance dose) or IFX (standard maintenance dose)/thiopurine (stable dose for at least 3 months) combination for <12 months.-

Exclusion Criteria:

  • Age< 18 years;
  • Patients treated with IFX at non-standard doses;
  • diagnosis of ulcerative colitis, pouchitis, indeterminate colitis or Crohn's disease involving the upper GI tract or perianal disease without involvement of small bowel or colon;
  • concomitant therapy with cyclosporine, methotrexate or other immunosuppressant other than thiopurine and IFX, treatment with IFX or IFX/thiopurine combination for > 12 months;
  • pregnancy

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
CD Monotherapy
Crohn's disease treated with infliximab (monotherapy)
Drug: Infliximab
Drug is prescribed by treating physician and is not a part of the study. This study is non-interventional. Patients, to be elgibile, are being prescribed either monotherapy inlfiximab or combo therapy infliximab with azathiopurine.
Other Names:
  • Remicade
CD Combo therapy
Crohn's disease treated with infliximab in combination with thiopurine (a 6MP metabolite) (combo therapy)
Drug: Infliximab
Drug is prescribed by treating physician and is not a part of the study. This study is non-interventional. Patients, to be elgibile, are being prescribed either monotherapy inlfiximab or combo therapy infliximab with azathiopurine.
Other Names:
  • Remicade
Drug: thiopurine
Drug is prescribed by treating physician and is not a part of the study. This study is non-interventional. Patients, to be elgibile, are being prescribed either monotherapy inlfiximab or combo therapy infliximab with azathiopurine.
Other Names:
  • Imuran

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
Correlation of 6-TGN serum levels with IFX serum trough levels
Time Frame: 52 weeks
Evaluate the correlation of 6-TGN serum levels with IFX serum trough levels , prevalence of ATI and clinical response treatment in CD patients treated with a combination of IFX and a thiopurine.
52 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluation of 6-TGN serum levels and IFX trough levels
Time Frame: 52 weeks
Evaluate the correlation of 6-TGN serum levels at the initial visit (week 14 or visit 1) with IFX serum trough levels, prevalence of ATI and clinical response at week 52.
52 weeks
6 TGN levels and dose escalation or disconinuation of IFX
Time Frame: 52 plus 6 months for data calculation
Determine the correlation of 6-TGN levels with need for dose escalation and discontinuation of IFX for the duration of the study.
52 plus 6 months for data calculation
Vitamin D levels and efficacy of anti-TNF therapy
Time Frame: duration of study and 1 additional year for data analysis
Evaluate the correlation of vitamin D levels (sufficient, insufficient, deficient) on the efficacy of anti-TNF therapy in patients with Crohn's disease.
duration of study and 1 additional year for data analysis
Vitamin D status and effect on ATI levels
Time Frame: duration of study and 1 additional year for data analysis
Determine the correlation between vitamin D status with trough IFX levels and the prevalence of ATI.
duration of study and 1 additional year for data analysis

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.
Ernest Seidman

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.
University of Alberta
University of Toronto
University of Calgary

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: Ernest Seidman, MDCM, McGill University Health Centre/Research Institute of the McGill University Health Centre

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.
November 17, 2014

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, 2019

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.
June 30, 2020

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).
May 21, 2015

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.
May 22, 2015

First Posted (ESTIMATE)

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.
May 25, 2015

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.
February 16, 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.
February 14, 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.
February 1, 2017

More Information

Terms related to this study

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.
  • 14-158-GEN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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 Crohn's Disease

Clinical Trials on Infliximab

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