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Regulatory T-cells and Crohn's Disease (CrohnReg)

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ClinicalTrials.gov Identifier: NCT02060318
Recruitment Status : Completed
First Posted : February 12, 2014
Last Update Posted : September 5, 2017
Sponsor:
Information provided by (Responsible Party):
Ove Andersen, Hvidovre University 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.


Condition or disease Intervention/treatment
Crohn Disease Drug: Infliximab

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.


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Study Type : Observational
Actual Enrollment : 47 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Infliximab Therapy in Crohn Patients on Regulatory T-cells
Actual Study Start Date : February 11, 2014
Actual Primary Completion Date : March 7, 2016
Actual Study Completion Date : March 7, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Infliximab

Group/Cohort Intervention/treatment
Infliximab
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.
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.

Healthy controls
12 healthy controls without Crohn's Disease.



Primary Outcome Measures :
  1. Change from baseline in number of regulatory T-cells at 6 weeks [ Time Frame: Baseline, 6 weeks (plus/minus 1 week) ]
    The number of regulatory T-cells is measured in fresh blood by flow cytometry.

  2. Change from baseline in number of regulatory T-cells at 22 weeks [ Time Frame: Baseline, 22 weeks (plus/minus 1 week) ]
    The number of regulatory T-cells is measured in fresh blood by flow cytometry.


Secondary Outcome Measures :
  1. Change from baseline in Harvey Bradshaw Index at 6 weeks [ Time Frame: Baseline, 6 weeks (plus/minus 1 week) ]
    Harvey Bradshaw Index is a measure of Crohn's Disease severity.

  2. Change from baseline in CD161 expression at 6 weeks [ Time Frame: Baseline, 6 weeks (plus/minus 1 week) ]
    Cluster of differentiation 161 (CD161) is a T helper 17 cell (Th17)-marker, measured by flow cytometry of fresh blood samples.

  3. Change from baseline in CD161 expression at 22 weeks [ Time Frame: Baseline, 22 weeks (plus/minus 1 week) ]
    CD161 is a Th17-marker, measured by flow cytometry of fresh blood samples.

  4. Change from baseline in cytokine levels at 6 weeks [ Time Frame: Baseline, 6 weeks (plus/minus 1 week) ]
    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.

  5. Change from baseline in cytokine levels at 22 weeks [ Time Frame: Baseline, 22 weeks (plus/minus 1 week) ]
    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.

  6. Change from baseline in Harvey Bradshaw Index at 22 weeks [ Time Frame: Baseline, 22 weeks (plus/minus 1 week) ]
    Harvey Bradshaw Index is a measure of Crohn's Disease severity.


Biospecimen Retention:   Samples With DNA
Serum, plasma, peripheral blood mononuclear cells.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02060318


Locations
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Denmark
Hvidovre Hospital
Hvidovre, Copenhagen, Denmark, 2650
Sponsors and Collaborators
Hvidovre University Hospital
Investigators
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Principal Investigator: Ove Andersen, MD, PhD Hvidovre Hospital & University of Copenhagen

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Responsible Party: Ove Andersen, MD, PhD, Hvidovre University Hospital
ClinicalTrials.gov Identifier: NCT02060318     History of Changes
Other Study ID Numbers: H-1-2013-072
HVH-2013-028 ( Registry Identifier: Datatilsynet )
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: September 5, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data sets will be made available on relevant requests and in accordance with journal guidelines when publishing results from this study.

Keywords provided by Ove Andersen, Hvidovre University Hospital:
Crohn Disease
Regulatory T-cells
Infliximab

Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents