Response To Medical Therapy in Inflammatory Bowel Disease Patients Carrying-out a Prescribed Exercise Programme

The Impact Of A Physician-led Exercise Programme On Quality Of Life, Muscle Mass And Clinical Response In Inflammatory Bowel Disease Patients During Induction With Medical Therapy

The investigators propose the use of a 20 week physician-derived exercise programme will lead to an improvement in physical fitness which will in turn lead to an increase in muscle mass, a reduction in visceral obesity resulting in an improvement in biologic response, disease biomarkers (including a reduction in circulating pro-inflammatory cytokines), fatigue scores and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Behavioral: Physician-prescribed Exercise Programme; Drug: Best Medical Therapy

Detailed Description

After completion, the investigators expect to describe the significant impact that exercise has on IBD disease control, response to biologics, modification of pro-inflammatory cytokine levels, quality of life and fatigue scores.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karen Boland, PhD; Phone Number: 018092810; Email: karenjboland@gmail.com
• Study Contact Backup: Name: Neasa Mc Gettigan, MB BCh, MSc; Phone Number: 018092810; Email: neasamcgettigan21@rcsi.com

Study Locations

• Ireland
  • Dublin, Ireland
    • Recruiting
    • Beaumont Hospital
    • Contact: Neasa Mc Gettigan; Phone Number: +35318092810; Email: neasamcgettigan21@rcsi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or above.
• Confirmed moderate to severe inflammatory bowel disease based on endoscopic evaluation, clinical scoring tools and faecal calprotectin.
• Be able to provide written informed consent.
• Stable dose of steroids.
• Physically able to complete an exercise programme.
• Healthy controls.

Exclusion Criteria:

• Inability to participate in the exercise program (unable to perform 6MWT, unable to attend for assessment of parameters at any time point).
• An uncontrolled cardiovascular condition such as unstable angina, uncontrolled cardiac arrhythmias, uncontrolled symptomatic heart failure or symptomatic severe aortic stenosis.
• A significant musculoskeletal condition, neurological condition, mental illness or intellectual disability that restricts participation in a physical exercise program.
• Pregnancy.
• Healthy controls with underlying inflammatory conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inflammatory Bowel Disease Exercise Group; The exercise group will be randomized to a 20-week physician-prescribed exercise programme following the principles of Frequency, Intensity, Time, and Type (FITT) in addition to best medical therapy with the aim of increasing physical fitness levels, inflammatory response, quality of life/fatigue improvements and favorable body composition changes.	Behavioral: Physician-prescribed Exercise Programme; A 20-week structured exercise programme derived and supervised by a Sports Medicine Physician following the FITT Principles; Drug: Best Medical Therapy; Best medical therapy with biologic agent or small-molecule therapy
Other: Inflammatory Bowel Disease Control Group; The IBD control group will be randomized to best medical therapy alone.	Drug: Best Medical Therapy; Best medical therapy with biologic agent or small-molecule therapy
No Intervention: Healthy Control Group; A group of healthy controls without inflammatory bowel disease will be included in the study for comparison of inflammatory markers including cytokine analysis and body composition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The recruitment rates in both IBD arms.	A calculation of the percentage of people approached who participate in the intervention (recruitment).	26 weeks
The retention rate in both IBD arms.	A calculation of the percentage of people approached who complete the intervention.	26 weeks
The adherence rate in both IBD arms.	A calculation of the percentage of people approached who adhered to the intervention.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle mass measured by ultrasound	Ultrasound of thigh muscle mass (vastus intermedius and rectus femoris-measured in mm, subcutaneous adiposity measured in mm)	26 weeks
Change in muscle mass measured by bioelectrical impedance analysis	Bioelectrical impedance analysis (muscle mass in Kg)	26 weeks
Change in visceral fat measured by bioelectrical impedance analysis	Bioelectrical impedance analysis (visceral fat in Kg)	26 weeks
Clinical remission in response to exercise intervention	Harvey Bradshaw Index 2 or lower in Crohn's disease patients or partial Mayo score 0-1in ulcerative colitis	12 and 26 weeks
Change in fatigue score between the IBD groups in response to exercise	Measured using the Fatigue Severity Scale which comprises nine statements, describing the severity and impact of fatigue, with a scale of possible responses ranging from 1 ("strongly disagree") to 7 ("strongly agree").	12 and 26 weeks
Change in Quality of Life in response to exercise	Measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ)- a ten item questionnaire, with 1 to 7 points for each item and higher scores indicating higher quality of life.	12 and 26 weeks
Change in endoscopic disease activity between IBD groups	A change in endoscopic appearance of Crohn's using Simple endoscopic score for Crohn's disease (SES CD) (inactive when SES-CD was 0-2; mild when 3-6; moderate 7-15; and severe >16) or Mayo score for ulcerative colitis (Score 0-3, Mayo 3 indicating severe disease, 2 moderate disease, 1 mild disease and 0 inactive).	26 weeks
Inflammatory response between IBD groups measured using C-Reactive protein	Change in C-Reactive Protein (mg/L)	12 and 26 weeks
Inflammatory response between IBD groups measured using faecal calprotectin	Change in faecal calprotectin (ug/g)	12 and 26 weeks
Inflammatory response between IBD groups measured using pro-inflammatory cytokines	Change in circulating pro-inflammatory cytokines (pg/mL)	12 and 26 weeks
Change in handgrip strength	Use of Jamar dynamometer to measure handgrip strength in kPa	12 and 26 weeks
A change in physical fitness between the IBD patient arms	15% difference in 6-minute walk test (6MWT) distance between the two groups	26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of metabolic markers in response to exercise	Analysis of key immunometabolic pathways including flow cytometry of peripheral T-cells	12 and 26 weeks
Adverse events	The frequency and nature of adverse events will be recorded (number, percentage and type).	26 weeks

Collaborators and Investigators

• Sponsor: Royal College of Surgeons, Ireland
• Investigators: Principal Investigator: Karen Boland, PhD, Royal College of Surgeons, Ireland and Beaumont Hospital, Dublin, Ireland.

Publications and helpful links

General Publications

• Elia J, Kane S. Adult Inflammatory Bowel Disease, Physical Rehabilitation, and Structured Exercise. Inflamm Bowel Dis. 2018 Nov 29;24(12):2543-2549. doi: 10.1093/ibd/izy199.
• Chan D, Robbins H, Rogers S, Clark S, Poullis A. Inflammatory bowel disease and exercise: results of a Crohn's and Colitis UK survey. Frontline Gastroenterol. 2014 Jan;5(1):44-48. doi: 10.1136/flgastro-2013-100339. Epub 2013 Jul 31.
• Cronin O, Barton W, Moran C, Sheehan D, Whiston R, Nugent H, McCarthy Y, Molloy CB, O'Sullivan O, Cotter PD, Molloy MG, Shanahan F. Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial. BMC Gastroenterol. 2019 Feb 12;19(1):29. doi: 10.1186/s12876-019-0952-x.
• Eckert KG, Abbasi-Neureither I, Koppel M, Huber G. Structured physical activity interventions as a complementary therapy for patients with inflammatory bowel disease - a scoping review and practical implications. BMC Gastroenterol. 2019 Jul 2;19(1):115. doi: 10.1186/s12876-019-1034-9.
• Gatt K, Schembri J, Katsanos KH, Christodoulou D, Karmiris K, Kopylov U, Pontas C, Koutroubakis IE, Foteinogiannopoulou K, Fabian A, Molnar T, Zammit D, Fragaki M, Balomenos D, Zingboim N, Ben Horin S, Mantzaris GJ, Ellul P. Inflammatory Bowel Disease [IBD] and Physical Activity: A Study on the Impact of Diagnosis on the Level of Exercise Amongst Patients With IBD. J Crohns Colitis. 2019 May 27;13(6):686-692. doi: 10.1093/ecco-jcc/jjy214.
• Jones K, Baker K, Speight RA, Thompson NP, Tew GA. Randomised clinical trial: combined impact and resistance training in adults with stable Crohn's disease. Aliment Pharmacol Ther. 2020 Sep;52(6):964-975. doi: 10.1111/apt.16002. Epub 2020 Jul 30.
• Jones PD, Kappelman MD, Martin CF, Chen W, Sandler RS, Long MD. Exercise decreases risk of future active disease in patients with inflammatory bowel disease in remission. Inflamm Bowel Dis. 2015 May;21(5):1063-71. doi: 10.1097/MIB.0000000000000333.
• Klare P, Nigg J, Nold J, Haller B, Krug AB, Mair S, Thoeringer CK, Christle JW, Schmid RM, Halle M, Huber W. The impact of a ten-week physical exercise program on health-related quality of life in patients with inflammatory bowel disease: a prospective randomized controlled trial. Digestion. 2015;91(3):239-47. doi: 10.1159/000371795. Epub 2015 Mar 24.
• Lamers CR, de Roos NM, Bongers CCWG, Ten Haaf DSM, Hartman YAW, Witteman BJM, Hopman MTE. Repeated prolonged moderate-intensity walking exercise does not appear to have harmful effects on inflammatory markers in patients with inflammatory bowel disease. Scand J Gastroenterol. 2021 Jan;56(1):30-37. doi: 10.1080/00365521.2020.1845791. Epub 2020 Nov 19.
• Loudon CP, Corroll V, Butcher J, Rawsthorne P, Bernstein CN. The effects of physical exercise on patients with Crohn's disease. Am J Gastroenterol. 1999 Mar;94(3):697-703. doi: 10.1111/j.1572-0241.1999.00939.x.
• Ng V, Millard W, Lebrun C, Howard J. Low-intensity exercise improves quality of life in patients with Crohn's disease. Clin J Sport Med. 2007 Sep;17(5):384-8. doi: 10.1097/JSM.0b013e31802b4fda.
• Afzal R, Dowling JK, McCoy CE. Impact of Exercise on Immunometabolism in Multiple Sclerosis. J Clin Med. 2020 Sep 21;9(9):3038. doi: 10.3390/jcm9093038.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Anticipated): March 22, 2023
• Study Completion (Anticipated): May 22, 2023

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): January 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 21-048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No