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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| paediatric Crohn's disease | Experimental | CD young population (ages 12-17 years) - N=20 |
|
| Healthy volunteers | Active Comparator | Age-, BMI- and gender-matched healthy volunteers (HV) - N=20 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Protein nutrition in paediatric Crohn's disease | Behavioral | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Assess protein intake | Detailed 3-days protein intake via Intake24 online questionnaire | 15 minutes/ history diary intake |
| Measure | Description | Time Frame |
|---|---|---|
| Assess calories, carbohydrate, fat and micronutrient intake | Detailed 3-day calorie, carbohydrate, fat and micronutrient intake via Intake24 online questionnaire | 15 minutes/ history diary intake |
| Assess eating behaviour |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bayan Aljilani, MSc | Contact | 07866010685 | mzxba1@exmail.nottingham.ac.uk | |
| Gordon Moran, PhD | Contact | 0115 9249924 | mszgwm@exmail.nottingham.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Gordon Moran, PhD | University of Nottingham | Principal Investigator |
| Kostas Tsintzas, PhD | University of Nottingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| David Greenfield Human Physiology Unit, B Floor, Medical school, Queens Medical centre | Recruiting | Nottingham | Nottinghamshire | NG7 2UH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18478564 | Background | Schneider SM, Al-Jaouni R, Filippi J, Wiroth JB, Zeanandin G, Arab K, Hebuterne X. Sarcopenia is prevalent in patients with Crohn's disease in clinical remission. Inflamm Bowel Dis. 2008 Nov;14(11):1562-8. doi: 10.1002/ibd.20504. | |
| 24332699 | Background | van Langenberg DR, Della Gatta P, Hill B, Zacharewicz E, Gibson PR, Russell AP. Delving into disability in Crohn's disease: dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease. J Crohns Colitis. 2014 Jul;8(7):626-34. doi: 10.1016/j.crohns.2013.11.024. Epub 2013 Dec 13. |
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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
7 years
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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|
Child Eating Behaviour, (CEBQ) questionnaire
| 10 minutes |
| Assess eating behaviour | Child Tree-Factor Eating Questionnaire (CTFEQr17) questionnaire | 10 minutes |
| Post-prandial protein digestibility | Postprandial plasma AA appearance/digestibility via collection of blood sample | 360 minutes |
| Assess body composition | Whole-body muscle mass using 3T | 30 minutes |
| Assess body composition | Whole-body muscle mass using 3T | Assess body composition |
| Measure serum inflammatory cytokines | Serum key cytokines and hormones: IL-1, IL-6, IL-10, IL-15, TNF, GH, IGF-1, testosterone | 15 minutes |
| Quantify muscle strength | Muscle strength will be assessed via maximal forearm contractions using a handgrip dynamometer | 30 minutes |
| Assess body composition | Intra-myocellular and extra-myocellular lipid content using 3T | 30 minutes |
| 11706295 | Background | Gassull MA, Cabre E. Nutrition in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):561-9. doi: 10.1097/00075197-200111000-00018. |
| 16534419 | Background | Filippi J, Al-Jaouni R, Wiroth JB, Hebuterne X, Schneider SM. Nutritional deficiencies in patients with Crohn's disease in remission. Inflamm Bowel Dis. 2006 Mar;12(3):185-91. doi: 10.1097/01.MIB.0000206541.15963.c3. |
| 16698129 | Background | Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schutz T, van Gemert W, van Gossum A, Valentini L; DGEM (German Society for Nutritional Medicine); Lubke H, Bischoff S, Engelmann N, Thul P; ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN Guidelines on Enteral Nutrition: Gastroenterology. Clin Nutr. 2006 Apr;25(2):260-74. doi: 10.1016/j.clnu.2006.01.007. Epub 2006 May 15. |
| 29617753 | Background | Wardle RA, Thapaliya G, Nowak A, Radford S, Dalton M, Finlayson G, Moran GW. An Examination of Appetite and Disordered Eating in Active Crohn's Disease. J Crohns Colitis. 2018 Jun 28;12(7):819-825. doi: 10.1093/ecco-jcc/jjy041. |
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| 31529051 | Background | Moughan PJ, Wolfe RR. Determination of Dietary Amino Acid Digestibility in Humans. J Nutr. 2019 Dec 1;149(12):2101-2109. doi: 10.1093/jn/nxz211. |
| 19625697 | Background | Koopman R, Walrand S, Beelen M, Gijsen AP, Kies AK, Boirie Y, Saris WH, van Loon LJ. Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men. J Nutr. 2009 Sep;139(9):1707-13. doi: 10.3945/jn.109.109173. Epub 2009 Jul 22. |
| 31910028 | Background | Tsintzas K, Jones R, Pabla P, Mallinson J, Barrett DA, Kim DH, Cooper S, Davies A, Taylor T, Chee C, Gaffney C, van Loon LJC, Stephens FB. Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men. Am J Physiol Endocrinol Metab. 2020 Mar 1;318(3):E417-E429. doi: 10.1152/ajpendo.00344.2019. Epub 2020 Jan 7. |
| 19474134 | Background | Koopman R, Crombach N, Gijsen AP, Walrand S, Fauquant J, Kies AK, Lemosquet S, Saris WH, Boirie Y, van Loon LJ. Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. Am J Clin Nutr. 2009 Jul;90(1):106-15. doi: 10.3945/ajcn.2009.27474. Epub 2009 May 27. |
| 7815181 | Background | Boirie Y, Fauquant J, Rulquin H, Maubois JL, Beaufrere B. Production of large amounts of [13C]leucine-enriched milk proteins by lactating cows. J Nutr. 1995 Jan;125(1):92-8. doi: 10.1093/jn/125.1.92. |
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| D007410 | Intestinal Diseases |