Clinical trial NCT05572203: Phenotyping of Adult Crohn's Focusing on Sarcopenia
Official title: Deep Nutritional Phenotyping of Adult Crohn's Disease Patients: a Focus on Protein Intake and Sarcopenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Inflammatory Bowel Diseases
Sarcopenia
Digestive System Disease
Nutrition, Healthy
Protein Malabsorption
Crohn Disease
Keywords: Labelled protein
protein
muscle protein synthesis
muscle mass
sarcopenia
Inflammatory bowel disease
Crohn's disease
nutrition
DEXA
13C/2H-labelled amino acids
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2022-10-07
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria for Healthy group

1. Aged 18 years or older
2. BMI \<30 kg/m2/
3. No previous known bowel disease
4. Be able to provide written informed consent \& participate fully in all aspects of the study.

Inclusion Criteria for Crohn's group:

1. Aged 18 years or older.
2. BMI \<30 kg/m2
3. Documented diagnosis of CD previously confirmed by endoscopy and histology at least 2 years prior to enrolment.
4. Active CD defined as HBI \>4 and CRP \>5g/l or FCP \>250ug/g or as deemed through endoscopy or cross sectional imaging.
5. Previous biologic or immunosuppressant exposure
6. Previous CD-related intestinal surgery
7. Able to participate fully in all aspects of the study
8. Written informed consent obtained and documented

Exclusion Criteria for Healthy group

1. Aged 18 years or older
2. BMI \<30 kg/m2/
3. No previous known bowel disease
4. Be able to provide written informed consent \& participate fully in all aspects of the study.

Exclusion Criteria for Crohn's group

1. A current diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, or diverticular disease-associated colitis
2. A diagnosis of short-bowel syndrome
3. Use of systemic corticosteroids for CD (2 continuous weeks or more) within 3 months prior to enrolment, or use of any medications for HVs and CD, in the opinion of the investigator, may interfere with the subject's ability to participate fully in the study.
4. 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.
5. History of active alcohol or drug abuse that, in the opinion of the investigator, may interfere with the subject's ability to comply with the study procedures.
6. Pregnancy or breastfeeding.
7. Contraindications for DEXAscanning e.g. x-ray within last 7 days.
8. Allergy to milk, , or casein

Primary outcomes:
measure: Postprandial muscle protein synthesis.
timeFrame: Change from baseline 4 hours (Two time points)
Secondary outcomes:
measure: Appearance/ digestibility of plasma Amino Acid in blood.
timeFrame: blood samples will be taken at regular intervals up to 240 minutes (max 120ml total blood draw post protein drink). 12-time points
measure: Muscle mRNA expression of anabolic and catabolic
timeFrame: Change from baseline at 4 hours (Two time points).
measure: Muscle protein expression of anabolic and catabolic pathway.
timeFrame: Change from baseline at 4 hours (Two time points).
measure: Serum Cytokines levels of IL-1
timeFrame: Only at baseline.
measure: Serum Cytokines levels of IL-6
timeFrame: Only at baseline.
measure: Serum Cytokines levels of IL-10
timeFrame: Only at baseline.
measure: Serum Cytokines levels of CRP
timeFrame: Only at baseline.
measure: Serum Cytokines levels of TNF
timeFrame: Only at baseline.
measure: Appendicular Lean Mass (ALM) to Height Ratio (Kg/Height2) through DEXA scan
timeFrame: Only at baseline
measure: Appendicular skeletal muscle index (ASMI; kg/m2) through DEXA scan.
timeFrame: Only at baseline
measure: Skeletal muscle index (SMI; kg/m2) through DEXA scan.
timeFrame: Only at baseline
measure: Skeletal Muscle Mass Percentage (SMM; %) through DEXA scan.
timeFrame: Only at baseline
measure: Total Body Fat Percentage (BF; %) through DEXA scan.
timeFrame: Only at baseline
measure: Fat Mass Index (FMI; kg/m2) through DEXA scan.
timeFrame: Only at baseline
measure: Resting Metabolic Rate (RMR) through DEXA scan.
timeFrame: Only at baseline
measure: Muscle Strength through Handgrip
timeFrame: Only at baseline
measure: Muscle Strength through Cybex Dynamometer
timeFrame: Only at baseline
measure: Daily physical activity
timeFrame: Only at baseline
measure: Quality of life for Crohn's disease patients
timeFrame: Only at baseline
measure: Dietary intake of one day before the experiment day.
timeFrame: Only at baseline
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
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