ProteIn Nutrition in Crohn's Disease (PINC)

Muscles are essential for good quality of life. The investigators have shown that when children with Crohn's disease eat protein, only very little of it enters the muscles, leading to poor muscle growth and fatigue. The investigators want to find the reasons for this. The investigators will recruit 20 Crohn's disease patients and a matched group of healthy kids. The investigators will measure: Daily food intake and muscle strength. Protein absorption by giving our participants a milk protein test drink and take regular blood samples after. Muscle mass with MRI. This study will help understand how protein is handled in these patients.

Muscle mass is maintained through the daily balance of muscle protein synthesis (MPS) and muscle protein breakdown (MPB), with the essential amino acid (EAA) components of a meal and muscle contraction being the primary stimulators of MPS. Adult patients with active CD ingest considerably less daily protein intake than age- BMI- matched healthy controls [CD, 70.3 g ± 6.1; HV, 92.6 g ± 7.8, p = 0.03]. Similar observations may be true for children with inactive CD where protein intake is lower with 79 ± 5g/day reported in CD and 90 ± 10g/day reported in HV. In male paediatric patients with long term CD, muscle metabolism is perturbed by a negative branched chain amino acid balance in the forearm. CD may have a significant effect on protein digestion and absorption, blunting the MPS response to feeding, leading to a chronic muscle mass reduction that may persist even when in remission. The essential amino acid (EAA) components of a protein-meal are crucial for the stimulation of muscle protein synthesis (MPS) and we have shown of all the EAA, leucine plays a key role in driving MPS. Low serum levels EAA/leucine have been reported in adult CD but their role in the aetiology of sarcopenia in paediatric CD is unknown. Further, how CD affects the protein digestion/absorption and how this contributes to low EAA/leucine remains unclear. Recent advances in stable isotope tracer techniques now enable a more accurate determination of protein digestibility. By following the appearance of intrinsically labelled AAs into the blood upon digestion of the intrinsically labelled protein, alongside the appearance of label-free AAs, protein digestibility can be accurately determined. Main aims: To accurately measure protein intake and fasting plasma EAA and non-EAA in paediatric CD. The investigators will use an intrinsically labelled protein milk to investigate protein digestion and absorption and link these findings to whole body muscle mass as measured through MRI.

Crohn's Disease (CD), Muscle Protein Synthesis, Muscle Protein Breakdown, Magnetic Resonance Imaging (MRI), Amino Acids (AAs), Essential Amino Acid (EAA)

All participants (N = 40) will undergo the same study procedures: Eating behaviour questionnaire(s) completion Duration: 5 minutes Frequency 2 Dietary intake data via online computerised recall Duration: 60 minutes Frequency: 3 Collection of blood sample via venepuncture Duration: 15 minutes Frequency 1 Strength Tests Duration: 30 minutes Frequency: 1 Half the participants (N = 20) will return for two more visits and will undergo the following procedures: MRI Scan Duration: 30 minutes Frequency: 1 Consumption of intrinsically labelled protein Duration: 15 minutes Frequency: 1 Insertion of cannulae into hand Duration: 15 minutes Frequency: 1 Collection of blood sample via cannulae (for protein digestion and inflammatory markers and study endpoints outlined below) Duration: 1 minute Frequency: 17

Inclusion Criteria: Age 12-17 years BMI <30 kg/m2 (all) **Documented diagnosis of CD previously confirmed by endoscopy and histology at least 6 months prior to enrolment (CD group only) **Stable CD defined as no change in medication in the last 3 months (including corticosteroids) and no CD-related surgical intervention in the last 6 months (CD group only) Able to participate fully in all aspects of the clinical trial (all) Written informed consent obtained and documented (all) **n/a to HV's Exclusion Criteria: A current diagnosis of UC, indeterminate colitis or microscopic colitis A diagnosis of short-bowel syndrome Serious underlying disease other than **CD that, in the opinion of the investigator, may interfere with the subject's ability to participate fully in the study Contraindications for MRI scanning e.g. pacemaker Dairy intolerance/milk protein allergy Non-English speakers **n/a to HV's

The samples provided by my child and the information gathered about my child can be stored by the University of Nottingham at the Research Tissue Bank (DI William Dunn-Licence Number 12265), for possible use in future studies

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