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

NCT02453607 | Unknown

• 1 other identifier: 14-158-GEN
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Inflammatory Bowel Disease; Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• Correlation of 6-TGN serum levels with IFX serum trough levels

  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 Outcomes (4)

• Evaluation of 6-TGN serum levels and IFX trough levels

  52 weeks

• 6 TGN levels and dose escalation or disconinuation of IFX

  52 plus 6 months for data calculation

• Vitamin D levels and efficacy of anti-TNF therapy

  duration of study and 1 additional year for data analysis

• Vitamin D status and effect on ATI levels

  duration of study and 1 additional year for data analysis

Study Arms (2)

CD Monotherapy

Crohn's disease treated with infliximab (monotherapy)

Drug: Infliximab

CD Combo therapy

Crohn's disease treated with infliximab in combination with thiopurine (a 6MP metabolite) (combo therapy)

Drug: Infliximab; Drug: thiopurine

Interventions

Infliximab DRUG

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.

Also known as: Remicade

CD Combo therapy; CD Monotherapy

thiopurine DRUG

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.

Also known as: Imuran

CD Combo therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.-

You may not qualify if:

• 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

Sponsors & Collaborators

• Ernest Seidman: lead
• University of Toronto: collaborator
• University of Calgary: collaborator
• University of Alberta: collaborator

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

We will be storing, de-identified, blood samples on site in the lab of Dr Ernest Seidman

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Interventions

Infliximab; 2-mercaptopurine; Azathioprine

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ernest Seidman, MDCM

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Diamond, BSc.,JD/MSEL

CONTACT

5149341934; melissa.diamond@mail.mcgill.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine & Pediatrics

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 25, 2015
• Study Start: November 17, 2014
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2020
• Last Updated: February 16, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)