NCT02370030

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
160

participants targeted

Target at P75+ for phase_1 sepsis

Timeline
Completed

Started Nov 2014

Typical duration for phase_1 sepsis

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2014

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

February 18, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 24, 2015

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

August 28, 2015

Status Verified

August 1, 2015

Enrollment Period

1.6 years

First QC Date

February 18, 2015

Last Update Submit

August 26, 2015

Conditions

Sepsis

Keywords

sepsiscitrullineendothelialtoxemiaendothelial determination of progressionwith vs without citrulline

Outcome Measures

Primary Outcomes (1)

  • Multiple organ failure

    Progression to multiple organ failure ending in death

    1 month

Study Arms (2)

Intervention

ACTIVE COMPARATOR

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

Dietary Supplement: Citrulline malate

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Citrulline malate

Interventions

Citrulline malateDIETARY_SUPPLEMENT

Active comparator: 10 g/day citrulline malate during 7 days

Also known as: Citrulline
InterventionPlacebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

CME Centro Mèdico Siglo XXI

Mexico City, Mexico City, 06720, Mexico

RECRUITING

CME La Raza

Mexico City, Mexico City, Mexico

RECRUITING

Related Publications (9)

  • Kao CC, Bandi V, Guntupalli KK, Wu M, Castillo L, Jahoor F. Arginine, citrulline and nitric oxide metabolism in sepsis. Clin Sci (Lond). 2009 Jun 2;117(1):23-30. doi: 10.1042/CS20080444.

    PMID: 19105791RESULT

  • Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.

    PMID: 17662768RESULT

  • Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC, Carbonnel F, Capellier G. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med. 2010 Apr;36(4):702-6. doi: 10.1007/s00134-010-1751-6.

    PMID: 20084502RESULT

  • Piton G, Belon F, Cypriani B, Regnard J, Puyraveau M, Manzon C, Navellou JC, Capellier G. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med. 2013 Sep;41(9):2169-76. doi: 10.1097/CCM.0b013e31828c26b5.

    PMID: 23782971RESULT

  • Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009 Jan;89(1):142-52. doi: 10.3945/ajcn.2007.25765. Epub 2008 Dec 3.

    PMID: 19056593RESULT

  • Kao C, Hsu J, Bandi V, Jahoor F. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1359-64. doi: 10.1152/ajpendo.00628.2012. Epub 2013 Apr 23.

    PMID: 23612995RESULT

  • Wijnands KA, Vink H, Briede JJ, van Faassen EE, Lamers WH, Buurman WA, Poeze M. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5):e37439. doi: 10.1371/journal.pone.0037439. Epub 2012 May 29.

    PMID: 22666356RESULT

  • Ware LB, Magarik JA, Wickersham N, Cunningham G, Rice TW, Christman BW, Wheeler AP, Bernard GR, Summar ML. Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis. Crit Care. 2013 Jan 17;17(1):R10. doi: 10.1186/cc11934.

    PMID: 23327349RESULT

  • Cynober L. Citrulline: just a biomarker or a conditionally essential amino acid and a pharmaconutrient in critically ill patients? Crit Care. 2013 Mar 11;17(2):122. doi: 10.1186/cc12534.

    PMID: 23509945RESULT

MeSH Terms

Conditions

SepsisToxemia

Interventions

citrulline malateCitrulline

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, DiaminoAmino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Eduardo Almeida Gutierrez, MSc

    Coordinación de Investigación en Salud, México.

    STUDY DIRECTOR

Central Study Contacts

Eduardo Almeida Gutierrez, MSc

CONTACT

+52-55-5627-6900almeida_90210@yahoo.com.mx

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head Researcher

Study Record Dates

First Submitted

February 18, 2015

First Posted

February 24, 2015

Study Start

November 1, 2014

Primary Completion

June 1, 2016

Study Completion

December 1, 2016

Last Updated

August 28, 2015

Record last verified: 2015-08

Locations

ME(2)