At a glance
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Non-invasive Approaches to Identify the Cause of Fatigue in Inflammatory Bowel Disease Patients
In Brief
A clinical study evaluating Muscle strength and fatigue assessment, Dual-energy X-ray absorptiometry (DEXA scan), and 3 other interventions for Crohn Disease. Completed, enrolled 45 participants across 1 site.
Detailed Summary
Crohn's disease (CD) presents with severe symptoms, but fatigue is a very predominant symptom that negatively impacts upon quality of life. Fatigue affects \~40% of patients when well and 80% of patients when the disease is active. It is the second commonest symptom that an IBD patient gets throughout their life-time. The IBD priority-setting partnership between the James Lind Alliance and the British Society of Gastroenterology has recently identified fatigue as an area of unmet clinical need and a priority research field, in which diagnosis and therapeutic intervention are lacking. Based on other diseases that present with fatigue, the cause of fatigue may be divided into peripheral fatigue, mainly driven by anomalies in muscle mass and function and central fatigue, mainly driven through decreased blood supply to the brain during exercise probably due to decreased heart and lung fitness. Research in IBD fatigue until now has been patchy with no convincing evidence that any treatment helps. There has been no research aimed at studying whole body function. It is imperative to have a better understanding of the alterations in muscle, brain, heart and lung function seen in these patients before specific treatments are researched. In this study, the investigators aim to recruit 32 CD patients, half with fatigue and half without. Subjects with active disease or with other known reasons of fatigue will be excluded. Findings in this group will be compared to 16 other healthy control volunteers of a similar age, gender and Body Mass Index. The study aims to recruit all participants over 36 months, and will target people aged from 16 to 60 years of age. Once recruited, the participants will be asked to provide their consent to take-part in 3 experiments on two separate days. These experiments have been designed to carefully consider potential fatigue burden, experimental practicality, and participant availability. Objective 1: The investigators aim to measure muscle fitness and strength by asking subjects to exercise using a stepper, whilst body mass and composition will be measured using an X-ray. This session will take 2 hours and be undertaken on one day. Objective 2: Peripheral fatigue: The investigators aim to non-invasively measure the recovery of muscle physiology after exercise by using magnetic resonance imaging after 5 min of exercise undertaken with a limb cuff. This will take \~1 hour. Objective 3: Central fatigue: while in the scanner and performing exercise, the investigators aim to non-invasively measure heart and brain blood flow before and after a few minutes of exercise using magnetic resonance imaging. This will take 2 hours. Experimental work for Objectives 2 and 3 will be undertaken on the same day. There will be ample time for recovery in between and during the different studies. There will be no further commitment from the participants required after these 2 study visits. IBD fatigue has never been studied in such detail. This unique work will allow identification of fatigue mechanisms, which can then be targeted with exercise, nutritional, or medical treatments.
Study Details
Timeline
Interventions
Measurement of maximum voluntary isometric contraction of the quadricep muscle on a cybex isokinetic dynomometer. This will be followed by a fatigue assessment where the torque decrement over 20 isokinetic knee extensions at a fixed angular velocity will be quantified to assess muscle fatigue
Body composition will be assessed via DEXA scan (Lunar Prodigy, GE Medical Systems, Bucks, UK)
VO2 peak will be quantified during completion of a continuous, incremental exercise test performed in the supine position on an MR adapted stepper machine (Ergospect, Innsbruck Austria)
Measurement of cardiac output and, cerebral and regional perfusion using Blood-Oxygen-level-dependent (BOLD) measures and arterial spin-labelling (ASL)-MRI as well as fractional oxygen extraction using TRUST-MRI during supine exercise of the quadriceps with the MR compatible cardiostepper (Ergospect, Innsbruck, Austria) at 50% of relative VO2 peak as measured during the supine cardiorespiratory fitness assessment.
Limb blood flow will be occluded with a cuff, whilst participants perform repeated plantar flexion exercise in a MRI scanner. This will drive PCr, (the available reserve of ATP) to zero. Once the cuff is removed, they will undergo non-invasive and well-established in vivo 31P magnetic resonance (31P MRS) measurements on the gastrocnemius to determine PCr re-synthesis rate during resting recovery.