Remote Ischemic Conditioning in Patients With Ulcerative Colitis

Sponsor

Odense University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02445365

Collaborator

University of Southern Denmark (Other), Aarhus University Hospital (Other)

Enrollment

Location

Arms

33.5

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD). At the time of diagnosis it is not possible to predict the course of the disease, which can range from a few flares in a lifetime to uncontrollable disease leading to hospitalization, surgery and stoma. There is a continuous need to improve treatment as well as diagnostic and prognostic tools.

This study evaluates the clinical efficacy, tolerability and feasibility of remote ischemic conditioning (RIC) in patients with moderate active ulcerative colitis (UC). The investigators hypothesize that RIC beyond the well known effect on reperfusion tissue damage has a clinically relevant anti-inflammatory effect in UC. RIC constitute a repeated brief and non-harmful suppression of blood circulation in a limb. The mechanism of action of RIC is likely to involve suppressed inflammation and cell death.

Our study is a randomized clinical controlled study including 38 patients. Patients will receive RIC or sham for 10 consecutive days.

The effect of RIC on active UC is evaluated by changes patient's symptoms, endoscopy findings, and various markers in the blood, faeces and the intestinal wall.

Condition or Disease	Intervention/Treatment	Phase
Colitis, Ulcerative Gastrointestinal Diseases Pathologic Processes Intestinal Diseases Inflammatory Bowel Diseases	Device: AutoRIC device	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

Effect of Remote Ischemic Conditioning (RIC) on Inflammation and Remodelling of Extracellular Matrix Proteins in Patients With Inflammatory Bowel Diseases

Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Feb 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active RIC Daily remote ischemic conditioning for 10 days. Remote ischemic conditioning is induced by placing a blood pressure cuff around the right or left arm. The cuff is inflated to 200 mmHg and the pressure is kept for 5 minutes. Hereafter the cuff is deflated for 5 minutes completing one cyclus. This cyclus is repeated 4 times.	Device: AutoRIC device
Sham Comparator: Sham As above with a cuff pressure of 20 mmHg	Device: AutoRIC device

Arm

Intervention/Treatment

Experimental: Active RIC

Daily remote ischemic conditioning for 10 days. Remote ischemic conditioning is induced by placing a blood pressure cuff around the right or left arm. The cuff is inflated to 200 mmHg and the pressure is kept for 5 minutes. Hereafter the cuff is deflated for 5 minutes completing one cyclus. This cyclus is repeated 4 times.

Device: AutoRIC device

Sham Comparator: Sham

As above with a cuff pressure of 20 mmHg

Device: AutoRIC device

Outcome Measures

Primary Outcome Measures

Change in index of clinical activity - numerical change in Mayo score including endoscopic subscore [10 days]

Secondary Outcome Measures

Change in fecal calprotectin. [10 days]
Change in endoscopy - central reading according to Mayo endoscopic subscore and UCEIS [10 days]
Number of patients achieving clinical remission (Mayo score <3) [10 days]
Patient experience of repeated RIC (questionnaire, including placebo recognition). [10 days]
Change in histological score of inflammation. [10 days]
Changes in serum and mucosal cytokine profile in particular Th1/Th2/Th9/Th17/Th22. measured by FlowCytomix Multiplex. [10 days]
Changes in serum markers of inflammation (serum C-reactive protein). [10 days]
Changes in serum markers of extracellular matrix proteins (C1M, C3M, C4M, P1NP and VICM). [10 days]
Changes in serum and mucosal level of CGRP, endothelin-1, endothelin-2. [10 days]
Effect of RIC in patients with active ulcerative colitis using the Langendorff model (to document activation of a cardioprotective response). [10 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age:≥18 years
Verified ulcerative colitis diagnosis according to clinical, endoscopic and histological standard criteria.
Diagnosis of ulcerative colitis established for at least 6 months
Moderate active ulcerative colitis, total Mayo score > 6
Endoscopic subscore activity grade ≥1
Written informed consent

Exclusion Criteria:

Pancolitis or acute severe ulcerative colitis requiring immediate treatment
Need for admission due to active ulcerative colitis
Ulcerative colitis with systemic symptoms (abdominal pain, fever > 37.5 degrees, weight loss exceeding 3 kilograms).
Patient with anemia (Haemoglobin < 8.3 mmol/l for males and < 7.3 mmol/l for females).
Patient with ostomy or pouch.
The patient has had a bowel resection (except appendectomy)
The patient has constipation and/or another known bowel condition than ulcerative colitis such as IBS.
The patient has diabetes.
Regular intake of acetylsalicylic acid or NSAIDs
The patient cannot understand the information material.
The patient has had colon cancer, dysplasia or adenomatous polyps in the colon during the recent 5 year
The patient is in a poor general condition.
The patient has had a food poisoning within the last three months.
The patient is pregnant at the time of inclusion or has planned pregnancy during the period of study.
The patient is in medical treatment with cyclosporine at the beginning of the run in period.
Treatment for ulcerative colitis treatment has been changed within two weeks before the first day in the run in period
The patient has commenced treatment with azathioprine, 6-mercaptopurine or methotrexate within 12 weeks before the first day in the run in period.
The patient has commenced treatment with TNF-α inhibitors within 12 weeks before the first day of the run in period.
The patient suffers from coeliac disease or lactose intolerance.
Antibiotic treatment within two weeks before the first day of the run in period.
Patient has any medical, surgical condition that excludes the use of RIC.