Crohn's Disease Clinical Trial
Official title:
Plasma Citrulline Level: A Simple, Sensitive Method to Assess and Monitor Small Bowel Absorptive Function in Patients With Crohn's Disease?
Citrulline is an amino acid produced in the intestine and in the liver, but the liver does
not contribute significantly to circulating citrulline concentrations. The intestine is thus
the only organ that normally releases significant amounts of citrulline into the blood. The
investigators have designed a study looking at the value of measuring plasma citrulline
concentration in patients with Crohn’s disease and short bowel or normal intestinal length.
Measuring the plasma citrulline concentration in short bowel patients may help to
distinguish between patients who need permanent parenteral feeding from patients with just
transient intestinal dysfunction. It may also help the investigators in understanding the
small bowel intestinal length remaining and the absorptive integrity. In patients with
normal intestinal length and Crohn’s disease, it may be a reliable marker of small bowel
damage and could be applied to establish therapeutic improvements. It has been demonstrated
to strongly correlate (inversely) with severity on intestinal biopsies.
The investigators hypothesise that the plasma citrulline concentration is a marker for small
bowel absorptive integrity and an appropriate surrogate for functional length of the small
intestine.
Controlled data do not yet exist to establish the place of plasma citrulline in the
assessment of small bowel function in man.
Preliminary studies reported that plasma citrulline concentrations may be a reliable
biochemical marker for intestinal dysfunction and absorptive enterocyte mass. The
relationship between citrulline concentration and intestinal function has been supported in
other studies including those examining rejection in small bowel allografts. Concentrations
of citrulline are dramatically reduced in cases of mucosal damage (e.g. moderate graft
rejection or viral enteritis) and strongly correlate (inversely) with severity on biopsy.
Plasma citrulline concentration is lower also in patients with villous atrophy (24±13
μmol/L) than in healthy subjects (40±10 μmol/L) and patients with anorexia nervosa (39±9).
A citrulline threshold of 20 µmol/L apparently permitted the classification of short bowel
syndrome patients into either transient or permanent intestinal failure categories, with 92%
sensitivity, 90% specificity, and 95% positive and 86% negative predictive values,
respectively. Experimental studies have been carried out also in assessing the value of
citrulline as a marker for severity of small bowel epithelial damage from radiation. The
plasma citrulline was shown to be a simple, non-invasive and sensitive assay to monitor and
quantify radiation-induced small bowel damage in mice and humans. Otherwise, the literature
on citrulline as a potential marker of intestinal and nutritional integrity is young and
data for specific conditions come only from single centres; there are limited data on normal
ranges. More crucially, however, there has been no attempt to clarify the effect of
inflammation on citrulline homeostasis. To date there is no information in respect of
patients with intestinal failure in whom there has been no resection.
We hypothesise that plasma citrulline concentration reflects small bowel absorptive capacity
and correlates to the functional intestinal length independently from inflammation.
Comparisons: To exclude the possibility that citrulline merely reflects inflammation,
control groups (six subjects each) with short bowel syndrome without inflammation
(mesenteric infarct) (negative control); and those with inflammation but no anatomical loss
(active coeliac disease) (positive controls); will be studied as well as healthy volunteers.
The study is designed to utilise patients from the positive and negative control groups to
permit a correlation of plasma citrulline with intestinal length and with a “gold standard”
assessment of intestinal function as judged from the patients need for nutritional
intervention (from normal diet to dependence on home parenteral nutrition).
Plasma citrulline will be determined by Reverse-phase High Performance Liquid Chromatography
(RF-HPLC) after an overnight fast. Albumin and Routine biochemical assessment will also be
performed. Gastrointestinal permeability will be determined from the double sugar test using
rhamnose and lactulose, and functional absorptive capacity will be estimated by D-Xylose
absorption rate.
Analysis will allow for paired comparison between patients and between groups. Differences
in the clinical performance of the various parameters will be determined. The study has
adequate statistical power.
;
Observational Model: Case Control, Time Perspective: Longitudinal
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03815851 -
Relationship Between Prophylactic Drainage and Postoperative Complications (PPOI) in Crohn's Patients After Surgery
|
N/A | |
Not yet recruiting |
NCT06100289 -
A Study of Vedolizumab in Children and Teenagers With Ulcerative Colitis or Crohn's Disease
|
Phase 3 | |
Completed |
NCT02883452 -
A Phase I Study to Evaluate Pharmacokinetics, Efficacy and Safety of CT-P13 Subcutaneous in Patients With Active Crohn's Disease and Ulcerative Colitis
|
Phase 1 | |
Recruiting |
NCT04777656 -
Use of Crohn's Disease Exclusion Diet on Top of Standard Therapy Versus Standard Therapy Alone in Unstable Pediatric Crohn's Disease Patients.
|
Phase 3 | |
Terminated |
NCT03017014 -
A Study to Assess Safety and Effectiveness of Adalimumab for Treating Children and Adolescents With Crohn's Disease in Real Life Conditions
|
||
Recruiting |
NCT06053424 -
Positron Emission Tomography Study of Changes in [11C]AZ14132516 Uptake Following Administration of AZD7798 to Healthy Participants and Patients With Crohn's Disease
|
Phase 1 | |
Recruiting |
NCT05428345 -
A Study of Vedolizumab SC Given to Adults With Moderate to Severe Ulcerative Colitis or Crohn's Disease in South Korea
|
||
Completed |
NCT02508012 -
Medico-economic Evaluation of the Therapeutic Drug Monitoring of Anti-TNF-α Agents in Inflammatory Bowel Diseases
|
N/A | |
Not yet recruiting |
NCT02858557 -
The Effect of Diet on Microbial Profile and Disease Outcomes in Patients With Inflammatory Bowel Diseases
|
N/A | |
Terminated |
NCT02882841 -
MOlecular BIomarkers and Adherent and Invasive Escherichia Coli (AIEC) Detection Study In Crohn's Disease Patients
|
N/A | |
Completed |
NCT03010787 -
A First Time in Human Study in Healthy Volunteers and Patients
|
Phase 1 | |
Completed |
NCT02542917 -
Home Versus Postal Testing for Faecal Calprotectin: a Feasibility Study
|
||
Terminated |
NCT02417974 -
Prevention of Recurrence of Crohn's Disease by Fecal Microbiota Therapy (FMT)
|
Phase 2 | |
Active, not recruiting |
NCT02316678 -
Patient Attitudes and Preferences for Outcomes of Inflammatory Bowel Disease Therapeutics
|
N/A | |
Completed |
NCT02154425 -
A Multicenter, Postmarketing Study Evaluating the Concentration of Cimzia® in Mature Breast Milk of Lactating Mothers
|
Phase 1 | |
Completed |
NCT02265588 -
Healthy Approach to Physical and Psychological Problems in Youngsters With IBD (HAPPY-IBD).
|
N/A | |
Completed |
NCT02197780 -
Head-to-head Comparison of Two Fecal Biomarkers to Screen Children for IBD
|
N/A | |
Completed |
NCT02193048 -
Prospective Evaluation of a Scoring System in Patients Newly Diagnosed With Crohn's Disease
|
||
Recruiting |
NCT02395354 -
Comparative Prospective Multicenter Randomized Study of Endoscopic Treatment of Stenosis in Crohn´s Disease
|
N/A | |
Completed |
NCT01951326 -
Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease
|
Phase 3 |