Phenotyping of Adult Crohn's Focusing on Sarcopenia
- Conditions
- Digestive System DiseaseCrohn DiseaseInflammatory Bowel DiseasesSarcopeniaNutrition, HealthyProtein Malabsorption
- Interventions
- Dietary Supplement: Intrinsically labelled protein
- Registration Number
- NCT05572203
- Lead Sponsor
- University of Nottingham
- Brief Summary
Inflammatory bowel disease (IBD) includes two idiopathic chronic relapsing and remitting inflammatory conditions affecting the gastrointestinal (GI) tract: Crohn's disease (CD) and ulcerative colitis (UC)Malnutrition and significant alteration of body composition are common in inflammatory bowel disease patients, whereby the prevalence of malnutrition may be up to 82.8% in CD patients with active disease, and up to 38.9% in CD patients in remission. Many CD patients have low muscle mass and function (sarcopenia) with drivers of such pathophysiology unknown. 41.6% of CD patients with sarcopenia require surgery, with the surgical trauma and resulting inactivity leading to further muscle mass loss such that the chronic inflammatory insult associated with refractory disease may be linked to advanced muscle mass depletion. The majority of adult CD patients have low muscle mass even in clinical remission indicating the poorly reversible nature of this phenomenon. Chronic disease burden may therefore be important in the accentuation of muscle loss.
Muscle mass is maintained through the daily balance of 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. Patients with active CD show a significant decrease in the expression of proteins in hypertrophic signalling pathways (Akt, P70S6K1) with no change in the expression of atrophic signalling (MAFbx, MuRF1). Also, adult CD patients with established disease consume less protein compared to matched healthy volunteers (HV). Furthermore, the intestinal motility, measured using cine-MRI, is reduced in active CD, possibly further decreasing intestinal digestion and absorption of dietary peptides. In general, the malabsorption is a major contributing factor to malnourishment in CD. It has been shown that in male paediatric patients with long-term CD, muscle metabolism is perturbed by a negative branched-chain amino acid balance in the forearm, with this variable linked to lower appendicular muscle mass, higher muscle fatigue and reduced protein intake, CD may have a significant effect on protein digestion and absorption, and blunt the MPS response to feeding, leading to a chronic muscle mass reduction that may persist even when in remission.
The EAA components of a protein meal are crucial for the stimulation of muscle protein synthesis (MPS), and all the EAA/leucine play a key role in driving MPS. Low serum levels EAA/leucine have been reported in CD but their role in the aetiology of sarcopenia in CD is unknown.
Further, how CD affects the protein digestion/absorption and how this contributes to low EAA/leucine unclear. Recent advances in stable isotope tracer techniques using a dual tracer methodology 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. Further, by collecting a muscle biopsy postprandially, the direct incorporation of AA from the digested protein into the muscle can be determined- providing a gold standard method for investigating anabolic resistance.
Project aim is to use an intrinsically labelled casein to investigate protein digestion, absorption and MPS responses in CD patients.
To achieve this, investigators will investigate protein digestion, absorption and muscle protein synthesis responses in Crohn's disease patients and healthy volunteers by utilising intrinsically labelled protein.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Crohn's group or patients group Intrinsically labelled protein This group will include patients with Crohn's disease. Healthy group (Control group ) Intrinsically labelled protein This group will include healthy participants matching Crohn's group
- Primary Outcome Measures
Name Time Method Postprandial muscle protein synthesis. Change from baseline 4 hours (Two time points) Postprandial muscle bound \[ring-D5\]-Phenylalanine, \[5,5,5-D3\]-Leucine as measured through mass spectrometry
- Secondary Outcome Measures
Name Time Method Serum Cytokines levels of IL-10 Only at baseline. As measured using ELISAs
Appendicular Lean Mass (ALM) to Height Ratio (Kg/Height2) through DEXA scan Only at baseline - It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scan will be a whole-body scan for total body composition measurement including ALM to height. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Skeletal muscle index (SMI; kg/m2) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scan will be a whole-body scan for total body composition measurement including SMI. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Muscle protein expression of anabolic and catabolic pathway. Change from baseline at 4 hours (Two time points). Muscle protein expression of anabolic and catabolic pathway signalling proteins
Appendicular skeletal muscle index (ASMI; kg/m2) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scan will be a whole-body scan for total body composition measurement including ASMI. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software
Total Body Fat Percentage (BF; %) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Resting Metabolic Rate (RMR) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Serum Cytokines levels of IL-6 Only at baseline. As measured using ELISAs
Serum Cytokines levels of TNF Only at baseline. Daily energy intake and dietary macronutrient composition
Muscle Strength through Handgrip Only at baseline Handgrip Dynamometers are instruments for measuring the maximum isometric strength of the hand and forearm muscles
Quality of life for Crohn's disease patients Only at baseline measured through the Short Quality of Life Questionnaire for Inflammatory Bowel Disease
Appearance/ digestibility of plasma Amino Acid in blood. blood samples will be taken at regular intervals up to 240 minutes (max 120ml total blood draw post protein drink). 12-time points Postprandial plasma \[ring-D5\]-Phenylalanine, \[5,5,5-D3\]-Leucine as measured through mass spectrometry
Muscle mRNA expression of anabolic and catabolic Change from baseline at 4 hours (Two time points). The mRNA expression of transcripts involved anabolic and catabolic signalling pathways as measured through RT-qPCR (Applied Biosystems).
Serum Cytokines levels of IL-1 Only at baseline. As measured using ELISAs
Serum Cytokines levels of CRP Only at baseline. As measured using ELISAs (IBDQ)
Daily physical activity Only at baseline Physical activity as measured with IPAQ
Skeletal Muscle Mass Percentage (SMM; %) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Fat Mass Index (FMI; kg/m2) through DEXA scan. Only at baseline It will be assessed via DEXA scan using a GE Lunar Prodigy DEXA scanner housed in the University of Nottingham's David Greenfield unit. The scans will be analysed using the scanners inbuilt Corescan software. Regional measurements will be taken post scan using custom analysis functions within the Corescan software.
Muscle Strength through Cybex Dynamometer Only at baseline A CYBEX Isokinetic Test is used to measure the maximum strength of a joint throughout its available range-of-motion (ROM).
Dietary intake of one day before the experiment day. Only at baseline As analysed by using intake24 website; https://intake24.co.uk/info/output . The participant will be received email included the link to fill it by what they intake on this day.
Trial Locations
- Locations (1)
University of Nottingham
🇬🇧Nottingham, United Kingdom