Regulatory T-cells and Crohn's Disease

Crohn Disease Clinical Trial

— CrohnReg  

Official title:

The Effect of Infliximab Therapy in Crohn Patients on Regulatory T-cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02060318
• Other study ID #: H-1-2013-072
• Secondary ID: HVH-2013-028
• Status: Completed
• Phase: N/A
• First received: February 10, 2014
• Last updated: August 31, 2017
• Start date: February 11, 2014
• Est. completion date: March 7, 2016

Study information

• Verified date: August 2017
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: March 7, 2016
• Est. primary completion date: March 7, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Denmark	Hvidovre Hospital	Hvidovre	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Hvidovre University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in number of regulatory T-cells at 6 weeks	The number of regulatory T-cells is measured in fresh blood by flow cytometry.	Baseline, 6 weeks (plus/minus 1 week)
Primary	Change from baseline in number of regulatory T-cells at 22 weeks	The number of regulatory T-cells is measured in fresh blood by flow cytometry.	Baseline, 22 weeks (plus/minus 1 week)
Secondary	Change from baseline in Harvey Bradshaw Index at 6 weeks	Harvey Bradshaw Index is a measure of Crohn's Disease severity.	Baseline, 6 weeks (plus/minus 1 week)
Secondary	Change from baseline in CD161 expression at 6 weeks	Cluster of differentiation 161 (CD161) is a T helper 17 cell (Th17)-marker, measured by flow cytometry of fresh blood samples.	Baseline, 6 weeks (plus/minus 1 week)
Secondary	Change from baseline in CD161 expression at 22 weeks	CD161 is a Th17-marker, measured by flow cytometry of fresh blood samples.	Baseline, 22 weeks (plus/minus 1 week)
Secondary	Change from baseline in cytokine levels at 6 weeks	We will measure IFN-gamma, IL-4, IL-6, IL-7, IL-10, IL-15, IL-17, and TNF-alpha by Luminex. TGF-beta, suPAR, and IL-15 will be measured by ELISA.	Baseline, 6 weeks (plus/minus 1 week)
Secondary	Change from baseline in cytokine levels at 22 weeks	We will measure IFN-gamma, IL-4, IL-6, IL-7, IL-10, IL-15, IL-17, and TNF-alpha by Luminex. TGF-beta, suPAR, and IL-15 will be measured by ELISA.	Baseline, 22 weeks (plus/minus 1 week)
Secondary	Change from baseline in Harvey Bradshaw Index at 22 weeks	Harvey Bradshaw Index is a measure of Crohn's Disease severity.	Baseline, 22 weeks (plus/minus 1 week)