Anti TNF α Improves Endothelial Dysfunction in IBD Patients

Study hypothesis - this study will assess the presence of endothelial dysfunction in patients with Crohn's disease before and after 12 weeks treatment of anti TNF α.

Study Overview

• Status: Unknown
• Conditions: Crohn's Disease
• Intervention / Treatment: Device: Endopath from Itamar medical - FDA approved device.; Drug: Anti TNF Alfa.

Detailed Description

Crohn's Disease (CD) is a life long disease that mainly affects young adults. There is evidence That gut tissue injury is the result of an abnormal immune response that involved multiple non immune cellular systems including the intestinal microvascular endothelial cell. Moreover, clinical studies have shown that 1-7% of irritable bowel disease (IBD) patients suffer from arterial and venous thromboembolic complication.

Chronic inflammation has a major role in the development and propagation of endothelial dysfunction, which can lead to coronary artery disease.

Endothelial dysfunction has been described in patients with various and diverse chronic inflammatory conditions. Over the last few years, dysfunction of vascular endothelium has been widely recognized as the first step in the development of atherosclerosis. Several inflammatory mediators, such as C-reactive protein (CRP), Tumor Necrosis Factor α, (TNF α), nitric oxide (NO), vascular endothelial growth factor, CD-40, interleukin-6 (IL-6), which are up-regulated in IBD, also are known to impact vascular impact.

The normal endothelium produces a vasodilatatory response to ischemia referred to us as reactive hyperemia. Shear stress on the blood vessel wall leads to the production and release vasodilatation. With endothelial dysfunction there is often either a blunted vasodilatatory in response to ischemic event, and chronic inflammation.

The hypothesis of this study is that patients with Crohn's disease have an increased incidence of endothelial dysfunction, which can be corrected or improved by treatment with anti TNF α.

The purpose of our study was to assess endothelial function in patients with Crohn's Disease, before and after treatment (steroids, immunomodulators, and anti TNF α). This study assessed the presence of endothelial dysfunction in patients with Crohn's disease and evaluated the possible role of tumor necrosis factor (TNF)-α in the pathophysiology of this abnormality.

In this study we will preformed an endothelial function test before and after treatment by Endopath device from Itamar medical, FDA approved.

Safety- Each subject will be screened by clinical history, physical examination, electrocardiogram, chest X-ray, Mantoux test (PPD), routine chemical analysis, and biomarkers.

The study protocol has been approved by the local institutional review board.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: zittan Eran, M.D; Phone Number: 972-48250359; Email: eranzittan@gmail.com
• Study Contact Backup: Name: Segol Ori, M.D; Phone Number: 972-4-8250359; Email: Ori_Segol@clalit.org.il

Study Locations

• Israel
  • Haifa, Israel
    • Recruiting
    • Carmel Medical Center
    • Principal Investigator: ZITTAN ERAN, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

IBD Patients.

Description

Inclusion Criteria:

• Non smoker
• No history of IHD or other known risk factors for IHD

Exclusion Criteria:

• Patients who had been treated with anti TNF α 4 weeks before the study
• As well as those who received corticosteroids within 1 week before the study.
• DM, IHD, CRF, SMOKER

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
endothelial dysfunction assessment; This study is a one arm study . In this arm we will assess endothelial function (with Endopath device) in patients with Crohn's disease, before and after treatment of anti TNF α and other medication, and evaluate the possible role of tumor necrosis factor (TNF)-α in the pathophysiology of this abnormality.	Device: Endopath from Itamar medical - FDA approved device.; endothelial function assessment by Endopath device; Drug: Anti TNF Alfa.; This study will assessed the presence of endothelial dysfunction in patients with Crohn's disease before and after 12 weeks treatment of anti TNF α.; Other Names: HUMIRA-ADALIMUMAB, REMICADE-INFLIXIMAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
This study will assessed the presence of endothelial dysfunction in patients, C with crohn's disease before and after 12 weeks treatment of anti TNF α. CDAI, CRP.	In this study we will preformed an endothelial function test before and after 12 weeks of treatment, by Endopath device from Itamar medical, FDA approved. Endo-PAT tests can be carried out in both the office and hospital settings, with patients positioned either sitting or supine. Endo-PAT bio-sensors are placed on the index fingers of both arms. The test takes 15 minutes to complete, is very easy to perform, and is both operator and interpreter independent. Thermo-neutral, quiet surroundings are recommended. Endo-PAT quantifies the endothelium-mediated changes in vascular tone, elicited by a 5-minute occlusion of the brachial artery (using a standard blood pressure cuff).	12 month

Collaborators and Investigators

• Sponsor: Carmel Medical Center
• Investigators: Principal Investigator: Zittan Eran, CARMEL MEDICAL CENTER - HAIFA -ISRAEL

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: June 11, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Estimate): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 15, 2014
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Adalimumab; Infliximab
• Other Study ID Numbers: CMC-13-0006-CTIL