Effect of Citrulline on the Clinical and Biochemical Evolution of Patients With Sepsis.

Phase 1

• Conditions: Sepsis
• Interventions: Dietary Supplement: Citrulline malate

• Registration Number: NCT02370030
• Lead Sponsor: Instituto Mexicano del Seguro Social

Brief Summary

Triple blind placebo-controlled study to determine if administering citrulline in patients with sepsis and severe sepsis slows progression to multiple organ failure and death, measuring biomarkers of endothelial dysfunction. Patients are divided into placebo or citrulline and followed up for 1 month.

Detailed Description

Consecutive patients with sepsis are being recited from intensive care unite of IMSS at the CMN Siglo XXI and CMN La Raza over the period of november 2015 through june 2016. After signing an informed consent they will be randomized into 80 for intervention arm and 80 for the placebo arm. All patients will receive usual medical treatment; and during seven days citurlline arm subjects will receive supplementation with oral or nasogastric citrulline (10 g/day), while other group patients will receive during seven days oral or nasogastric placebo (10 g/day) with no visible difference between these. Microalbuminuria and interleukines 1, 6, and 10 will be measured at randomization and at day 7. All subjects will be followed for 28 days, and after the follow-up period results will be analyzed to determine de efficacy and safety of citrulline, primary outcome are the incidence of multiple organic failure and death, also microalbuminuria levels 1,6,10-interleukines. We will use Student-t and Chi2 for statistical analysis.

Study Timeline

• Study Start: 2014-11
• Study First Submitted: 2015-02-18
• Study First Submitted QC: 2015-02-23
• Study First Posted: 2015-02-24
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-26
• Last Update Posted: 2015-08-28
• Primary Completion: 2016-06
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

• Sepsis
• Severe sepsis
• Diagnosis of sepsis in the first 36 hours of hospitalization.
• Informed Consent
• Intestinal tract intact

Exclusion Criteria

• Terminal cancer
• Acute and chronic liver diseases
• Chronic renal failure.
• Acute renal failure AKIN III.
• Pregnant and postpartum women
• Dying patients.
• Patients with cardiac arrest.
• Active gastrointestinal bleeding.
• Steroids or immunosuppressants.
• Enrolled in another study intervention.
• Citrulline allergy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Citrulline malate	Oral or nasogastric administration of 10 g citrulline malate daily. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA
Placebo	Citrulline malate	10 g of maltodextrin will be substituted for the citrulline. Blood and urine samples to determine biomarkers of endothelial damage (IL 6, IL 10 , nitric oxide and microalbuminuria), with a second sampling after 7 days of intervention. Disease severity will be measure with various scales, including APACHE II, SOFA

Primary Outcome Measures

Name	Time	Method
Multiple organ failure	1 month	Progression to multiple organ failure ending in death

Trial Locations

Locations (2)

CME La Raza; 🇲🇽 Mexico City, DF, Mexico

CME Centro Mèdico Siglo XXI; 🇲🇽 Mexico City, DF, Mexico