Clinical trial NCT00684736: Tryptophan, Serotonin and Kynurenine in Septic Shock
Official title: Tryptophan, Serotonin and Kynurenine in Septic Shock
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Shock, Septic
Keywords: septic shock
shock
serotonin
kynurenine
tryptophan
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2008-05-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who were 18 years of age or older and had been hospitalized in our ICU were prospectively enrolled in the study if they met all eligibility criteria. Inclusion criteria were clinical evidence of infection, evidence of a systemic response to infection, and the onset of shock within the previous 3 hours.

Brief summary: Septic shock is a major cause of mortality and morbidity worldwide. Serotonin (5-HT) is released by activated platelets into the circulation, and is mediator of endothelial dysfunction. 5-HT metabolism is known in immune system via specific 5-HT receptor, also in effects on the peripheral nervous system. Kinetic of 5-HT, tryptophan, kynurenine, MAO activity and IDO activity in human septic shock was never investigated.


Eligibility criteria: Inclusion Criteria:

* Age above or equal to 18 years
* Strong presumption clinical sepsis
* Need for mechanical ventilation
* Body temperature above 38°C or below 36°C
* Heart rate above 90 bpm
* Systolic blood pressure of \<90mm Hg despite adequate fluid replacement or a need for vasopressors less than 3 hours
* Presence of at least one of the following criteria:

  * Ratio of arterial oxygen tension over inspired fraction of oxygen of less than 300 mm Hg
  * Urinary output below 0.5 mL per kg of bodyweight per h or below 30 mL/h (for at least 1 h)
  * Arterial lactate concentration above 2 mmol/L
* Consent signed

Exclusion Criteria:

* Age below 18 years
* Pregnancy
* Underlying disease with a poor prognosis, a life expectancy of less than 24 hours
* Depression or melancholy
* Neuropsychiatric diseases: Seizure, manic psychosis, Migraine, or Drug addiction
* Neuroendocrine tumors
* Obstructive cardiomyopathy or acute myocardial ischaemia
* Pulmonary embolism
* Advanced stage cancer, malignant haemopathy, or AIDS with a decision to withhold or withdraw aggressive therapies
* Inclusion in another clinical trial
* Patient who receive before inclusion one of the following treatment known to modify serotonin level: almotriptan, amitriptyline, amoxapine, citalopram, clomipramine, clozapine, desipramine, dihydroergotamine, dolasetron, dosulepin, doxepin, eletriptan, ergotamine, flunarizine, fluoxetine, fluvoxamine, granisetron, imipramine, indoramin, interferon Alfa, interferon alfacon-1, interferon beta, iproniazid, maprotiline, methysergide, mianserin, Milnacipran, mirtazapine, moclobemide, naratriptan, olanzapine, ondansetron, oxetorone, paroxetine, pizotifen, risperidone, sertraline, sumatriptan, tianeptine, trimipramine, tropisetron, venlafaxine,viloxazine, zolmitriptan.
* No consent

Primary outcomes:
measure: Kinetics of 5-HT, 5-HIAA, kynurenine, tryptophan, HVA, VMA, DOPAC, Oestradiol, Cotinine and vasopressors
timeFrame: Day-1, Day-2, Day-3, Day-7 and Day-14
Secondary outcomes:
measure: Mortality
timeFrame: 28-day
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: CH Versailles - André Mignot Hospital
Study officials:
affiliation: Versailles Hospital
name: Jean-Pierre Bédos, MD, PhD
role: STUDY_CHAIR
affiliation: Versailles Hospital
name: Odile Spreux-Varoquaux, PhD
role: STUDY_DIRECTOR
affiliation: Versailles Hospital
name: Matthieu Henry-Lagarrigue, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Troche G, Henry-Lagarrigue M, Soppelsa F, Legriel S, Yehia A, Bruneel F, Bedos JP, Spreux-Varoquaux O. Tryptophan pathway catabolites (serotonin, 5-hydroxyindolacetic acid, kynurenine) and enzymes (monoamine oxidase and indole amine 2,3 dioxygenase) in patients with septic shock: A prospective observational study versus healthy controls. Medicine (Baltimore). 2020 May;99(19):e19906. doi: 10.1097/MD.0000000000019906.