Nutrition and Clinical Outcomes in IBD

Not yet recruiting

• Conditions: Crohn Disease; Ulcerative Colitis; Malnutrition; Inflammatory Bowel Diseases; Sarcopenia

• Registration Number: NCT06550310
• Lead Sponsor: Barts & The London NHS Trust

Brief Summary

The goal of this observational study is to demonstrate that nutritional status and body composition have an impact on clinical outcomes in inflammatory bowel disease (IBD).

The main objectives are:

1. To compare the detection rates of undernutrition between a range of nutritional screening tools, physiological measures and assessment tools amongst patients with different IBD phenotypes

2. To correlate nutritional status, nutritional biomarkers and body composition with clinical outcomes in patients with IBD treated with advanced medical therapy or surgery

3. To determine a potential relationship between radiological muscle mass measurements and clinical outcomes in patients with IBD treated with advanced medical therapy or surgery

Participants will undergo an assessment at pre-treatment baseline and then again at their scheduled follow-up. This is a non-interventional study and participants will not be required to have any invasive tests or hospital visits beyond that of standard clinical care.

Detailed Description

Background and Rationale:

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). It affects nearly 400,000 people in the United Kingdom (UK) and the global prevalence is rising. Many patients suffer an impaired quality of life. Whilst advanced medical therapies are being used more often, the lifetime risk of surgery is as high as 70%. Unfortunately, loss of response to medical therapies and post-operative complications remain major clinical challenges. Risk factors for adverse treatment outcomes include disease duration, emergency surgery and undernutrition. Not only is undernutrition a risk factor for adverse clinical outcomes, it is present in up to 36% of patients with IBD. Crucially, unlike other risk factors, it is also modifiable with cheap and safe interventions. It therefore presents an ideal opportunity for intervention. Despite this, current methods of detecting undernutrition in IBD are unfit for purpose.

Body composition (BC) analysis is emerging as a highly clinically relevant physiological marker in IBD. Skeletal muscle loss with functional impairment (sarcopenia) in IBD patients is associated with a range of outcomes including disease flares, hospitalisation, need for surgery and need for ICU admissions. Radiological measurement of skeletal muscle index (SMI) at the level of the 3rd lumbar vertebra is objective and reproducible. Validated software designed specifically for this purpose (Slice-o-Matic \[Tomovision, Canada\]) can be used on CT/MRI scans which are often performed as part of standard IBD care. However, despite this, BC analysis by any method is not performed in routine clinical practice. The most commonly used physiological markers in the UK remain weight and body mass index (BMI), which do not provide any measure of BC.

Overall, there remains uncertainty over which nutritional tools should be used in patients with IBD. Most studies have been small, retrospective and heterogenous. No study has performed a comparative analysis of more than three measurements in the same patient cohort. Evidence of the ability of widely used nutritional screening tools to identify IBD patients most at risk of adverse clinical outcomes is lacking. Finally, there is little data describing the performance of different tools and measures according to disease phenotype and disease activity. This study proposes to meet this knowledge gap by comparing a range of nutritional tools in a large, prospective, well-phenotyped IBD cohort.

Study design:

Eligible patients will be identified from dedicated IBD multi-disciplinary weekly meetings, IBD clinic, medical infusion suites and the medical records. The clinical team will be aware of the study and can also flag potential eligible patients to the investigators. Participants will be contacted or approached directly in clinic or via telephone.

This will be a prospective, non-interventional study performed at Barts Health National Health Service (NHS) Trust over 4 years. For patients treated with advanced medical therapies, the entire prospective dataset will be collected at a pre-treatment baseline (within 4 weeks before treatment) and at weeks 14 and 52 after therapy commencement. For patients undergoing surgery, data will be collected at a pre-operative baseline (within 4 weeks before surgery) and at 3 months post-operatively. Data relating to dietetic input and artificial nutritional support will be included. The following outcomes from medical therapy will be collected at weeks 14 and 52: clinical response, clinical and biochemical remission, corticosteroid use, therapy switch, IBD-surgery. The following surgical outcomes will be collected: length of post-operative stay, formation of unplanned stoma, 30-day complication rate, 30-day complication grade (defined by the Clavien-Dindo scale) and 90-day readmission rate. Participants will then be followed-up longitudinally over the aforementioned defined timepoints. Muscle mass measurements will be performed by exporting CT/MRI image slices at the level of the third vertebra from Trust computers and using Slice-O-Matic software to measure skeletal muscle indices (SMI). Additionally, we will access de-identified CT/MRI scans from 946 well-phenotyped patients who have undergone IBD surgery collected by the national UK IBD Bioresource and made available via the Gut Reaction initiative hosted by the National Institute for Health and Care Research (NIHR). Post-operative outcome data will also be available, enabling this to be used as an external validation cohort to the primary surgical dataset. Within the internal cohort, handgrip strength and timed up and go test (TUG) or gait speed will be performed prospectively at scheduled visits, to assess muscle strength and physical performance respectively. All nutritional parameters collected will be correlated with clinical outcomes.

The clinical data that will be collected is outlined below:

Demographics: age, gender, ethnicity, comorbidities, smoking status, postcode IBD phenotype: diagnosis, duration, disease location and behaviour (CD), disease extent (UC) IBD treatment: current IBD therapy (\>3 months), previous IBD therapy, previous IBD-related surgery IBD activity: Harvey Bradshaw Index (HBI) or partial Mayo scores, C-reactive protein (CRP), faecal calprotectin Nutritional screening tools: Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screening Tool-2002 (NRS-2002), Malnutrition Inflammation Risk Tool (MIRT) Nutritional assessment tools: Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria Weight, height, BMI, anthropometry (waist circumference, mid-upper arm circumference, triceps skinfold thickness, mid-arm muscle circumference) Handgrip strength Timed up and go test (TUG) or gait speed Bioelectrical impedance analysis, including skeletal muscle mass (kg), body fat (%) and visceral adiposity (kg) Blood tests: Haemoglobin, folate, ferritin, B12, vitamin D, zinc, copper, selenium Dietetics: dietetic review, special diets, presence and type of artificial nutritional support Food intake (24-hour food diaries) Food frequency questionnaire Food-related quality of life questionnaire Skeletal muscle index

The end of recruitment will be month 18 for the medical arm and month 27 for the surgical arm, to allow sufficient time for follow-up and data analysis. The End of Study will be defined as the conclusion of follow-up monitoring, data analysis and write-up at month 36.

Analysis:

Descriptive statistics will be taken at baseline for both medical and surgical cohorts. These exploratory variables will be measured at the three timepoints (as outlined above) to compare if any statistically significant difference is present. Statistical significance will be considered if a threshold of p=0.05. One-way repeated measures analysis of variance (ANOVA) will be performed for both groups.

Further sub-group analysis to determine correlations between the exploratory variables and outcomes will be performed using multi-linear and binary logistic regression. Standard demographical analysis will be collected and further sub-group analysis based on ethnicity may be performed.

Ethical approval has been obtained from the Health Research Authority.

This study is sponsored by Barts Health NHS Trust.

There are no conflicts of interest.

Study Timeline

• Study First Submitted: 2024-07-31
• Study First Submitted QC: 2024-08-09
• Study First Posted: 2024-08-13
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05
• Study Start: 2025-09
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Patients with inflammatory bowel disease (Crohn's disease, ulcerative colitis or IBD-U) starting a new advanced medical therapy
• Patients with inflammatory bowel disease (Crohn's disease, ulcerative colitis or IBD-U) undergoing an IBD-related surgery
• Age >16
• Patients able and willing to provide written informed consent

Exclusion Criteria

• Patients below the age of 16
• Patients who cannot provide informed consent
• Patients with a cardiac pacemaker or internal defibrillator
• Patients with active cancer and other disorders associated with severe cachexia

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Correlation of nutritional parameters (at baseline and during treatment) with pre-defined clinical outcomes in patients undergoing advanced medical therapy (at 14 and 52 weeks).	14 and 52 weeks	Clinical outcomes are as follows clinical response, clinical and biochemical remission, corticosteroid use, therapy switch or IBD related-surgery.; Clinical response in UC is defined as a ≥2-point and ≥30% decrease from baseline in partial Mayo score and a ≥1-point decrease from baseline in rectal bleeding sub-score or an absolute rectal bleeding sub-score ≤1. Clinical response in CD is defined as ≥ 3 points decrease of HBI score. Clinical remission is defined as a partial Mayo score of 0-1 in UC or HBI of ≤4 in CD. Biochemical remission is defined as faecal calprotectin \<200μg/mg and CRP ≤5mg/L.
Correlation of nutritional parameters (at baseline and during treatment) with pre-defined clinical outcomes in patients undergoing IBD-related surgery (at 30 and 90 days).	30 and 90 days	Clinical outcomes are defined as length of post-operative stay, formation of unplanned stoma, 30-day complication rate, 30-day complication grade (defined by the Clavien-Dindo scale) and 90-day readmission rate.

Secondary Outcome Measures

Name	Time	Method
Correlation of currently used radiological muscle mass thresholds with pre-defined clinical outcomes in patients undergoing advanced medical therapy (at 14 and 52 weeks).	14 and 52 weeks	Clinical outcomes are as follows clinical response, clinical and biochemical remission, corticosteroid use, therapy switch or IBD related-surgery.; Clinical response in UC is defined as a ≥2-point and ≥30% decrease from baseline in partial Mayo score and a ≥1-point decrease from baseline in rectal bleeding sub-score or an absolute rectal bleeding sub-score ≤1. Clinical response in CD is defined as ≥ 3 points decrease of HBI score. Clinical remission is defined as a partial Mayo score of 0-1 in UC or HBI of ≤4 in CD. Biochemical remission is defined as faecal calprotectin \<200μg/mg and CRP ≤5mg/L.
Correlation of currently used radiological muscle mass thresholds with pre-defined clinical outcomes in patients undergoing advanced IBD-related surgery (at 30 and 90 days).	30 and 90 days	Clinical outcomes are defined as length of post-operative stay, formation of unplanned stoma, 30-day complication rate, 30-day complication grade (defined by the Clavien-Dindo scale) and 90-day readmission rate.