Clinical trial NCT02060318: Regulatory T-cells and Crohn's Disease
Official title: The Effect of Infliximab Therapy in Crohn Patients on Regulatory T-cells
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn Disease
Keywords: Crohn Disease
Regulatory T-cells
Infliximab
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2014-02-12
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from the gastroenterology department at Hvidovre Hospital and Køge Sygehus are eligible for entry.

Healthy controls are recruited by advitising at Hvidovre Hospital.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in number of regulatory T-cells at 6 weeks
timeFrame: Baseline, 6 weeks (plus/minus 1 week)
measure: Change from baseline in number of regulatory T-cells at 22 weeks
timeFrame: Baseline, 22 weeks (plus/minus 1 week)
Secondary outcomes:
measure: Change from baseline in Harvey Bradshaw Index at 6 weeks
timeFrame: Baseline, 6 weeks (plus/minus 1 week)
measure: Change from baseline in CD161 expression at 6 weeks
timeFrame: Baseline, 6 weeks (plus/minus 1 week)
measure: Change from baseline in CD161 expression at 22 weeks
timeFrame: Baseline, 22 weeks (plus/minus 1 week)
measure: Change from baseline in cytokine levels at 6 weeks
timeFrame: Baseline, 6 weeks (plus/minus 1 week)
measure: Change from baseline in cytokine levels at 22 weeks
timeFrame: Baseline, 22 weeks (plus/minus 1 week)
measure: Change from baseline in Harvey Bradshaw Index at 22 weeks
timeFrame: Baseline, 22 weeks (plus/minus 1 week)
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
state: Copenhagen
Study officials:
affiliation: Hvidovre Hospital & University of Copenhagen
name: Ove Andersen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: