Remote Ischemic Conditioning in Patients With Ulcerative Colitis
Primary Purpose
Colitis, Ulcerative, Gastrointestinal Diseases, Pathologic Processes
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
AutoRIC device
Sponsored by
About this trial
This is an interventional basic science trial for Colitis, Ulcerative focused on measuring Ulcerative colitis, Remote ischemic conditioning
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.
Sites / Locations
- Odense University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Active RIC
Sham
Arm Description
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.
As above with a cuff pressure of 20 mmHg
Outcomes
Primary Outcome Measures
Change in index of clinical activity - numerical change in Mayo score including endoscopic subscore
Secondary Outcome Measures
Change in fecal calprotectin.
Change in endoscopy - central reading according to Mayo endoscopic subscore and UCEIS
Number of patients achieving clinical remission (Mayo score <3)
Patient experience of repeated RIC (questionnaire, including placebo recognition).
Change in histological score of inflammation.
Changes in serum and mucosal cytokine profile in particular Th1/Th2/Th9/Th17/Th22. measured by FlowCytomix Multiplex.
Changes in serum markers of inflammation (serum C-reactive protein).
Changes in serum markers of extracellular matrix proteins (C1M, C3M, C4M, P1NP and VICM).
Changes in serum and mucosal level of CGRP, endothelin-1, endothelin-2.
Effect of RIC in patients with active ulcerative colitis using the Langendorff model (to document activation of a cardioprotective response).
Full Information
NCT ID
NCT02445365
First Posted
May 12, 2015
Last Updated
March 21, 2018
Sponsor
Odense University Hospital
Collaborators
University of Southern Denmark, Aarhus University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02445365
Brief Title
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
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
February 2018 (Actual)
Study Completion Date
February 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Odense University Hospital
Collaborators
University of Southern Denmark, Aarhus University Hospital
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative, Gastrointestinal Diseases, Pathologic Processes, Intestinal Diseases, Inflammatory Bowel Diseases
Keywords
Ulcerative colitis, Remote ischemic conditioning
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active RIC
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
As above with a cuff pressure of 20 mmHg
Intervention Type
Device
Intervention Name(s)
AutoRIC device
Primary Outcome Measure Information:
Title
Change in index of clinical activity - numerical change in Mayo score including endoscopic subscore
Time Frame
10 days
Secondary Outcome Measure Information:
Title
Change in fecal calprotectin.
Time Frame
10 days
Title
Change in endoscopy - central reading according to Mayo endoscopic subscore and UCEIS
Time Frame
10 days
Title
Number of patients achieving clinical remission (Mayo score <3)
Time Frame
10 days
Title
Patient experience of repeated RIC (questionnaire, including placebo recognition).
Time Frame
10 days
Title
Change in histological score of inflammation.
Time Frame
10 days
Title
Changes in serum and mucosal cytokine profile in particular Th1/Th2/Th9/Th17/Th22. measured by FlowCytomix Multiplex.
Time Frame
10 days
Title
Changes in serum markers of inflammation (serum C-reactive protein).
Time Frame
10 days
Title
Changes in serum markers of extracellular matrix proteins (C1M, C3M, C4M, P1NP and VICM).
Time Frame
10 days
Title
Changes in serum and mucosal level of CGRP, endothelin-1, endothelin-2.
Time Frame
10 days
Title
Effect of RIC in patients with active ulcerative colitis using the Langendorff model (to document activation of a cardioprotective response).
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Kjeldsen, MD, PhD
Organizational Affiliation
Odense University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Line Godskesen
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
12. IPD Sharing Statement
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Remote Ischemic Conditioning in Patients With Ulcerative Colitis
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