Clinical trial NCT00816842: Plasma Citrulline Concentration in Tropical Enteropathy
Official title: Plasma Citrulline as Quantitative Biomarker of HIV Associate Villous Atrophy in a Tropical Enteropathy Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malabsorption Syndromes
Granulomatous Enteritis
Enteritis
HIV Enteropathy
Ileal Diseases
Keywords: citrulline
malabsorption
Villous atrophy
enteropathy
Lead sponsor: Azienda Ospedaliero-Universitaria di Parma
Sponsor class: OTHER
First posted: 2009-01-05
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Tropical enteropathy with mixed HIV status

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 stream. The investigators have designed a study looking at the value of measuring plasma citrulline concentration in patients with tropical enteropathy of mixed HIV status. The focus will be on the ability of the intestine to sustain the individual concerned from a nutritional standpoint. The investigators hypothesise that plasma citrulline concentration is a marker of small bowel absorptive integrity and an appropriate surrogate for HIV related enteropathy.

Detailed description: 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±13µmol/L)than in healthy subjects (40±10µmol/L)and patients with anorexia nervosa (39±9µmol/L).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 and viral infections. The plasma citrulline was shown to be a simple, non invasive and sensitive essay to monitor and quantify radiation and/or chemotherapy 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 consistent data for specific conditions as for HIV enteropathy are missing.We hypothesise that plasma citrulline concentration is a marker of small bowel absorptive integrity and an appropriate surrogate for HIV related enteropathy.

Eligibility criteria: Inclusion Criteria:

* histologically ascertained Tropical enteropathy
* Mixed HIV status
* Body mass index within normal range

Exclusion Criteria:

* Patients with surgical resection of stomach, duodenum or pancreas; or (UGI) bypass.
* 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
* Patients experiencing diarrhoea within one month since enrolment date
* Use of glucagon-like peptide 2 (GLP2), growth hormone (GH) or glutamine or triglycerides
* Coeliac Disease, Crohn's disease or infectious intestinal disease
* Patients on steroids or FANS
* Oral feeding\>1.0-fold the estimated basal metabolic rate as assessed using Harris and Benedict equation

Primary outcomes:
measure: postabsorptive plasma citrulline concentration
timeFrame: within two years since enrolment date
Secondary outcomes:
measure: intestinal permeability ratio
timeFrame: within two years since enrolment date
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Department of Medicine, University of Zambia School of Medicine, University Teaching Hospital
state: Lusaka province
Study officials:
affiliation: Azienda Ospedaliero-Universitaria di Parma
name: Cinzia Papadia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University College London Hospitals
name: Alastair Forbes, BSc MD FRCP ILTM
role: STUDY_CHAIR
affiliation: University of Pavia
name: Antonio Di Sabatino, MD
role: STUDY_DIRECTOR
References: