Clinical trial NCT02445365: Remote Ischemic Conditioning in Patients With Ulcerative Colitis
Official title: Effect of Remote Ischemic Conditioning (RIC) on Inflammation and Remodelling of Extracellular Matrix Proteins in Patients With Inflammatory Bowel Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colitis, Ulcerative
Gastrointestinal Diseases
Pathologic Processes
Intestinal Diseases
Inflammatory Bowel Diseases
Keywords: Ulcerative colitis
Remote ischemic conditioning
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: University of Southern Denmark
name: Aarhus University Hospital
First posted: 2015-05-15
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in index of clinical activity - numerical change in Mayo score including endoscopic subscore
timeFrame: 10 days
Secondary outcomes:
measure: Change in fecal calprotectin.
timeFrame: 10 days
measure: Change in endoscopy - central reading according to Mayo endoscopic subscore and UCEIS
timeFrame: 10 days
measure: Number of patients achieving clinical remission (Mayo score <3)
timeFrame: 10 days
measure: Patient experience of repeated RIC (questionnaire, including placebo recognition).
timeFrame: 10 days
measure: Change in histological score of inflammation.
timeFrame: 10 days
measure: Changes in serum and mucosal cytokine profile in particular Th1/Th2/Th9/Th17/Th22. measured by FlowCytomix Multiplex.
timeFrame: 10 days
measure: Changes in serum markers of inflammation (serum C-reactive protein).
timeFrame: 10 days
measure: Changes in serum markers of extracellular matrix proteins (C1M, C3M, C4M, P1NP and VICM).
timeFrame: 10 days
measure: Changes in serum and mucosal level of CGRP, endothelin-1, endothelin-2.
timeFrame: 10 days
measure: Effect of RIC in patients with active ulcerative colitis using the Langendorff model (to document activation of a cardioprotective response).
timeFrame: 10 days
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Jens Kjeldsen, MD, PhD
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Line Godskesen
role: PRINCIPAL_INVESTIGATOR
References: