Citrulline: A Plasmatic Marker to Assess and Monitor Small Bowel Crohn's Disease Patients

NCT00138879 | Completed

• 1 other identifier: EC3155
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Crohn's Disease; Short Bowel Syndrome; Malabsorption Syndromes; Celiac Disease

Keywords

Citrulline; Parenteral Nutrition; functioning intestinal mass; small bowel permeability and absorption; Granulomatous Enteritis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Crohn's disease (CD) with massive small bowel resection at least 24 months previously (\< 50cm remaining)
• Crohn's disease with small bowel resection at least 24 months previously (50-150cm remaining)
• CD with no resection
• Mesenteric infarction with massive resection \> 24 months previously (\< 50cm remaining)
• Mesenteric infarction with massive resection \> 24 months previously (50-150cm remaining); coeliac disease.
• Healthy volunteers.
• Body mass index within the normal range

You may not qualify if:

• Patients with surgical resection of stomach, duodenum or pancreas; or upper gastrointestinal (UGI) bypass.
• Oral feeding \> 1.0-fold the estimated basal metabolic rate as assessed using Harris and Benedict equations.
• Patients with fistulating Crohn's disease
• Patients on steroids
• Patients with other important disease, which may interfere with the study (especially diabetes and renal impairment). Alcoholism, drug abuse or any other circumstances, which may compromise the patient's ability to comply with the study requirements.
• Pregnancy.
• Corticosteroid use or octreotide during, or in, the month before the study.
• Use of glucagon-like peptide 2 (GLP2), growth hormone (GH) or glutamine or triglycerides.

Sponsors & Collaborators

• St Mark's Hospital Foundation: lead

Study Sites (1)

St Mark's Hospital

London, Middlesex, HA1 3JX, United Kingdom

Location

Related Publications (15)

• Blijlevens NM, Lutgens LC, Schattenberg AV, Donnelly JP. Citrulline: a potentially simple quantitative marker of intestinal epithelial damage following myeloablative therapy. Bone Marrow Transplant. 2004 Aug;34(3):193-6. doi: 10.1038/sj.bmt.1704563.

  PMID: 15170165 BACKGROUND

• Lutgens LC, Deutz NE, Gueulette J, Cleutjens JP, Berger MP, Wouters BG, von Meyenfeldt MF, Lambin P. Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage. Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):1067-74. doi: 10.1016/s0360-3016(03)00781-8.

  PMID: 14575838 BACKGROUND

• Pappas PA, Tzakis AG, Saudubray JM, Gaynor JJ, Carreno MR, Huijing F, Kleiner G, Rabier D, Kato T, Levi DM, Nishida S, Gelman B, Thompson JF, Mittal N, Ruiz P. Trends in serum citrulline and acute rejection among recipients of small bowel transplants. Transplant Proc. 2004 Mar;36(2):345-7. doi: 10.1016/j.transproceed.2003.12.007.

  PMID: 15050154 BACKGROUND

• Selvaggi G, Weppler D, Tzakis A. Liver and gastrointestinal transplantation at the University of Miami. Clin Transpl. 2003:255-66.

  PMID: 15387117 BACKGROUND

• Pappas PA, G Tzakis A, Gaynor JJ, Carreno MR, Ruiz P, Huijing F, Kleiner G, Rabier D, Kato T, Levi DM, Nishida S, Gelman B, Thompson JF, Mittal N, Saudubray JM. An analysis of the association between serum citrulline and acute rejection among 26 recipients of intestinal transplant. Am J Transplant. 2004 Jul;4(7):1124-32. doi: 10.1111/j.1600-6143.2004.00469.x.

  PMID: 15196071 BACKGROUND

• Pappas PA, Saudubray JM, Tzakis AG, Rabier D, Carreno MR, Gomez-Marin O, Huijing F, Gelman B, Levi DM, Nery JR, Kato T, Mittal N, Nishida S, Thompson JF, Ruiz P. Serum citrulline as a marker of acute cellular rejection for intestinal transplantation. Transplant Proc. 2002 May;34(3):915-7. doi: 10.1016/s0041-1345(02)02668-4. No abstract available.

  PMID: 12034237 BACKGROUND

• Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B. Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003 May;124(5):1210-9. doi: 10.1016/s0016-5085(03)00170-7.

  PMID: 12730862 BACKGROUND

• Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505. doi: 10.1053/gast.2000.20227.

  PMID: 11113071 BACKGROUND

• Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol. 1981 Dec;241(6):E473-80. doi: 10.1152/ajpendo.1981.241.6.E473.

  PMID: 7325229 BACKGROUND

• Nightingale JM, Bartram CI, Lennard-Jones JE. Length of residual small bowel after partial resection: correlation between radiographic and surgical measurements. Gastrointest Radiol. 1991 Fall;16(4):305-6. doi: 10.1007/BF01887374.

  PMID: 1936771 BACKGROUND

• D'Antiga L, Dhawan A, Davenport M, Mieli-Vergani G, Bjarnason I. Intestinal absorption and permeability in paediatric short-bowel syndrome: a pilot study. J Pediatr Gastroenterol Nutr. 1999 Nov;29(5):588-93. doi: 10.1097/00005176-199911000-00021.

  PMID: 10554128 BACKGROUND

• Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker S, Mendelson RA, Jeejeebhoy KN. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987 Jan-Feb;11(1):8-13. doi: 10.1177/014860718701100108.

  PMID: 3820522 BACKGROUND

• Zhang WZ, Kaye DM. Simultaneous determination of arginine and seven metabolites in plasma by reversed-phase liquid chromatography with a time-controlled ortho-phthaldialdehyde precolumn derivatization. Anal Biochem. 2004 Mar 1;326(1):87-92. doi: 10.1016/j.ab.2003.11.006.

  PMID: 14769339 BACKGROUND

• Sherwood RA. Amino acid measurement by high-performance liquid chromatography using electrochemical detection. J Neurosci Methods. 1990 Sep;34(1-3):17-22. doi: 10.1016/0165-0270(90)90037-g.

  PMID: 2259239 BACKGROUND

• Sherwood RA, Titheradge AC, Richards DA. Measurement of plasma and urine amino acids by high-performance liquid chromatography with electrochemical detection using phenylisothiocyanate derivatization. J Chromatogr. 1990 Jun 29;528(2):293-303. doi: 10.1016/s0378-4347(00)82388-9.

  PMID: 2384569 BACKGROUND

MeSH Terms

Conditions

Crohn Disease; Short Bowel Syndrome; Malabsorption Syndromes; Celiac Disease; Hyperphagia

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms

Study Officials

• Alastair Forbes, Medicine

  University College, London

  STUDY CHAIR

• Roy A. Sherwood, Biochemistry

  King's College Hospital NHS Trust

  STUDY DIRECTOR

• Cinzia Papadia, Medicine

  Imperial College University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: August 30, 2005
• Study Start: May 1, 2003
• Study Completion: June 1, 2005
• Last Updated: December 15, 2005

Record last verified: 2005-08

Locations

GB (1)