Overview

This trial is active, not recruiting.

Condition crohn disease
Treatment infliximab
Target TNF-alpha
Sponsor Hvidovre University Hospital
Start date February 2014
End date October 2016
Trial size 47 participants
Trial identifier NCT02060318, H-1-2013-072, HVH-2013-028

Summary

Aim: the main aim of this study is to investigate if immune cells (regulatory T-cells, Th17 cells and other immune cell types) or biomarkers can be used to predict the response or lack of response to treatment with Infliximab. If so, characteristics of the immune cells may also unveil the mechanisms behind lack of response to Infliximab.

Design: a prospective, observational study with three arms. In the treatment group, 35 patients with Crohn's disease about to start Infliximab-treatment are recruited. They have blood samples drawn at day 1 before first treatment, after 6 week, and again after 22 weeks of treatment. 12 healthy volunteers serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines, and data from this study is not used by the clinicians.

Methods: the number of regulatory T-cells and pro-inflammatory T-cells (Th17 cells) is investigated using flow cytometry. From plasma and serum samples, various proteins (biomarkers), such as transforming growth factor beta (TGF-beta) and tumour necrosis factor alpha (TNF-alpha), are measured using immunoassays. Patient data (demographics and medical history) are extracted from various registries.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Arm
35 Crohn patients about to start Infliximab treatment, gives as i.v. injection of 5 mg/kg at baseline, after 2 weeks, 6 weeks, and then every 8th week.
infliximab
The patients are included in the study when the decision to treat with Infliximab is already made. This study is observational, and all treatment and clinical follow-up are according to national guidelines.
12 healthy controls without Crohn's Disease.

Primary Outcomes

Measure
Change from baseline in number of regulatory T-cells at 6 weeks
time frame: Baseline, 6 weeks (plus/minus 1 week)
Change from baseline in number of regulatory T-cells at 22 weeks
time frame: Baseline, 22 weeks (plus/minus 1 week)

Secondary Outcomes

Measure
Change from baseline in Harvey Bradshaw Index at 6 weeks
time frame: Baseline, 6 weeks (plus/minus 1 week)
Change from baseline in CD161 expression at 6 weeks
time frame: Baseline, 6 weeks (plus/minus 1 week)
Change from baseline in CD161 expression at 22 weeks
time frame: Baseline, 22 weeks (plus/minus 1 week)
Change from baseline in cytokine levels at 6 weeks
time frame: Baseline, 6 weeks (plus/minus 1 week)
Change from baseline in cytokine levels at 22 weeks
time frame: Baseline, 22 weeks (plus/minus 1 week)
Change from baseline in Harvey Bradshaw Index at 22 weeks
time frame: Baseline, 22 weeks (plus/minus 1 week)

Eligibility Criteria

Male or female participants at least 18 years old.

Infliximab group Inclusion Criteria: - Crohn's Disease - Starting Infliximab treatment - Patient at the gastrointestinal department at Hvidovre Hospital or Køge Sygehus - Can understand and write Danish - European ancestry Exclusion Criteria: - Not able to consent in an ethical manner (e.g. severe mental illness) - Significant co-morbidity (e.g. cancer, HIV) - Other immunological disease (e.g. psoriasis) - Current treatment with biological agents Healthy controls Inclusion Criteria: - No current disease - No daily drug use - Can understand and write Danish - European ancestry Exclusion Criteria: - Not able to consent in an ethical manner (e.g. severe mental illness) - Significant co-morbidity (e.g. cancer, HIV) - Other immunological disease (e.g. psoriasis) - Current treatment with biological agents

Additional Information

Official title The Effect of Infliximab Therapy in Crohn Patients on Regulatory T-cells
Principal investigator Ove Andersen, MD, PhD
Description Primary analyses: patient response to Infliximab treatment is quantified using Harvey Bradshaw Index, and the response is then related to the number of regulatory T-cells, Th17 cells, and biomarker levels at baseline. The exact cut-off for response vs. non-respons will be determined and validated once all data is collected by an assessor blinded for the flow cytometry results and biomarker levels. Plan for missing data: for patients with missing Harvey Bradshaw Index, we will first try to re-create the score using the patient records (information on well-being, abdominal pain, diarrhea, fistulae/abscesses, and extra-intestinal Crohn manifestations). If this is not possible, an experienced clinician will rate the patient's Infliximab response based on all available patient record data, but blinded for flow cytometry results and biomarker levels.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Hvidovre University Hospital.