An interventional study of Intrinsically labelled protein in Inflammatory Bowel Diseases, Sarcopenia and Digestive System Disease, sponsored by University of Nottingham. Status unknown at 1 site in United Kingdom. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-12-08.
Sponsored by University of Nottingham · Not applicable, Interventional, and Basic science
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.
1,487 studies on the registry are indexed under Inflammatory Bowel Diseases; 434 are open to participants now.
This study's planned enrollment of 35 is below the median of 70 across 783 interventional studies indexed under Inflammatory Bowel Diseases.
Browse Inflammatory Bowel Diseases studies →University of Nottingham is the lead sponsor of 463 studies on the registry; 78 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria for Healthy group
Inclusion Criteria for Crohn's group:
Exclusion Criteria for Healthy group
Exclusion Criteria for Crohn's group
This group will include healthy participants matching Crohn's group
Dietary Supplement: Intrinsically labelled protein
This group will include patients with Crohn's disease.
Dietary Supplement: Intrinsically labelled protein
It is a protein drink that includes Intrinsically labelled Casein ( from Arla Foods), 13C/2H-labelled Spirulina (from CK Isotopes), and 13C/2H-labelled amino acids (from CK Isotopes)
Also known as: Intrinsically labelled Casein
Postprandial muscle protein synthesis.
Postprandial muscle bound \[ring-D5\]-Phenylalanine, \[5,5,5-D3\]-Leucine as measured through mass spectrometry
Time frame: Change from baseline 4 hours (Two time points)
Appearance/ digestibility of plasma Amino Acid in blood.
Postprandial plasma \[ring-D5\]-Phenylalanine, \[5,5,5-D3\]-Leucine as measured through mass spectrometry
Time frame: blood samples will be taken at regular intervals up to 240 minutes (max 120ml total blood draw post protein drink). 12-time points
Muscle mRNA expression of anabolic and catabolic
The mRNA expression of transcripts involved anabolic and catabolic signalling pathways as measured through RT-qPCR (Applied Biosystems).
Time frame: Change from baseline at 4 hours (Two time points).
Muscle protein expression of anabolic and catabolic pathway.
Muscle protein expression of anabolic and catabolic pathway signalling proteins
Time frame: Change from baseline at 4 hours (Two time points).
Serum Cytokines levels of IL-1
As measured using ELISAs
Time frame: Only at baseline.
Serum Cytokines levels of IL-6
As measured using ELISAs
Time frame: Only at baseline.
Serum Cytokines levels of IL-10
As measured using ELISAs
Time frame: Only at baseline.
Serum Cytokines levels of CRP
As measured using ELISAs (IBDQ)
Time frame: Only at baseline.
Serum Cytokines levels of TNF
Daily energy intake and dietary macronutrient composition
Time frame: Only at baseline.
Appendicular Lean Mass (ALM) to Height Ratio (Kg/Height2) through DEXA scan
\- 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.
Time frame: Only at baseline
Appendicular skeletal muscle index (ASMI; kg/m2) through DEXA scan.
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
Time frame: Only at baseline
Skeletal muscle index (SMI; kg/m2) through DEXA scan.
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.
Time frame: Only at baseline
Skeletal Muscle Mass Percentage (SMM; %) through DEXA scan.
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.
Time frame: Only at baseline
Total Body Fat Percentage (BF; %) through DEXA scan.
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.
Time frame: Only at baseline
Fat Mass Index (FMI; kg/m2) through DEXA scan.
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.
Time frame: Only at baseline
Resting Metabolic Rate (RMR) through DEXA scan.
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.
Time frame: Only at baseline
Muscle Strength through Handgrip
Handgrip Dynamometers are instruments for measuring the maximum isometric strength of the hand and forearm muscles
Time frame: Only at baseline
Muscle Strength through Cybex Dynamometer
A CYBEX Isokinetic Test is used to measure the maximum strength of a joint throughout its available range-of-motion (ROM).
Time frame: Only at baseline
Daily physical activity
Physical activity as measured with IPAQ
Time frame: Only at baseline
Quality of life for Crohn's disease patients
measured through the Short Quality of Life Questionnaire for Inflammatory Bowel Disease
Time frame: Only at baseline
Dietary intake of one day before the experiment day.
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.
Time frame: Only at baseline
Plan to share: Undecided
Started Apr 2022 (actual). Primary completion is estimated for Jun 2023, 13 months after the start.
Of 286 non-industry interventional studies with no phase under Inflammatory Bowel Diseases, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 51. This study's planned 13 months is below that.
Counting every sponsor, half of 299 studies reached it within 28 months; a quarter within 14 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.