Remote Ischemic Conditioning in Patients With Ulcerative Colitis

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

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Diseases; Pathologic Processes; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis, Ulcerative
• Intervention / Treatment: Device: AutoRIC device

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in index of clinical activity - numerical change in Mayo score including endoscopic subscore	10 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Aarhus University Hospital; University of Southern Denmark
• Investigators: Study Chair: Jens Kjeldsen, MD, PhD, Odense University Hospital; Principal Investigator: Line Godskesen, Odense University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 15, 2018

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 15, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Remote ischemic conditioning
• Additional Relevant MeSH Terms: Gastroenteritis; Colonic Diseases; Ulcer; Inflammatory Bowel Diseases; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colitis, Ulcerative; Pathologic Processes
• Other Study ID Numbers: S-20140133