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TSK (Tryptophan - Serotonin - Kynurenine) Biomarkers Assessment in Stroke

Simultaneous Assessments of Serotonin and Kynurenine Pathways Parameters in Patients Shortly (Less Than 4 Hours and a Half) After the Onset of a Cerebral Infarction

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02963545
Enrollment
28
Registered
2016-11-15
Start date
2012-10-31
Completion date
2016-05-31
Last updated
2016-11-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cerebral Infarction

Brief summary

Single-center, prospective, descriptive and biomedical research with controls, without health product. Depression is the second risk factor for stroke as tobacco smoking following hypertension. Peripheral abnormalities in serotonin parameters were described in depression and tobacco smoking. The investigators hypothesized dysregulations in pathways of serotonin (5-HT), which has notably complex vasomotor effects and of kynurenine which could have cognitive dysfunction effects. The aim of this study is to evaluate simultaneously the involvement of serotonin and kynurenine pathways parameters in patients suffering from a cerebral infarction shortly after the onset (less than 4 hours and a half), within a 2 days follow-up (Day 1 and Day 2) and 3 months after the cerebral infarction.

Detailed description

Tryptophan (TRP), an essential aminoacid, is metabolized in the serotonin (5-HT) or in the kynurenine (KYN) pathway. Serotonin is catabolized to 5-HIAA (5-hydroxyindole amino acid) by monoamine oxidase A (MAOA). The TRP to KYN transformation is regulated by indoleamine 2,3-dioxygenase (IDO). The primary objective was the measurements of serotonin and kynurenine pathways parameters which were performed in blood and urine samples using different HPLC techniques and of serotonin transporters and receptors which were determined in blood platelets. The results in patients were compared to those measured in controls matched for age, gender, tobacco consumption and season of inclusion. The secondary objective was to evaluate the potential relationships between these 5-HT and Kyn pathways biomarkers concentrations, MAOA and IDO enzymatic activations and clinical outcome and criteria.

Interventions

OTHERUsual care patients in neurology department

patients characteristics, history, clinical signs chronology and usual medical care by the emergency units, cerebral infarction area

BIOLOGICALblood and urines sampling

Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations

depression scale, impulsivity scale, hostility scale , tobacco consumption questioning

Sponsors

Versailles Hospital
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

Study population : patients who had positive MRI diagnosis of cerebral infarction less than 4.30 hours after the clinical onset. Experimental group : Inclusion Criteria: * Age ≥ 18 ans * Cerebral infarction with a medical care to emergencies less than 4.30 hours after the symptoms onset. * Written informed consent signed by the patient, or by a trusted person then by the patient himself if permitted by his condition.

Exclusion criteria

* Cerebral infarction with a medical care to emergencies more than 4.30 hours after the symptoms onset. * Patient with subarachnoid haemorrhage, cerebral hematoma. * Pregnant woman * Patient under guardianship or trusteeship, or safeguard justice. Control group : * Matching criteria for age, gender, tobacco smoking, inclusion season

Design outcomes

Primary

MeasureTime frameDescription
Measure of kynurenin pathway parameters in blood samplesDay 1The first and regulatory enzyme of the kynurenine pathway is the indoleamine-2,3-dioxygenase (IDO). Plasma tryptophan (µM) and plasma kynurenine (µM) concentrations \[Trp\] and \[Kyn\] were quantified with HPLC method. \[Trp\] / \[Kyn\] ratio (in AU, Arbitrary Units) was used as index for IDO activity .
Measure of serotonin pathway parameters concentrations in blood and urine samplesDay 1platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods.
Measure of serotonin pathway parameters in blood samplesDay 1Blood platelets assessements of serotonin (5-HT) transporters using \[3H\]paroxetine ligand ( fmol/mg proteins) and 5-HT2A receptors using \[3H\]MDL-100,907 ligand ( fmol/mg proteins)
Measure of serotonin pathway parameters in blood and urine samplesDay 2platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods

Other

MeasureTime frameDescription
Patient characteristics, history, clinical signs chronologyDay 1For patients: patient characteristics, history, clinical signs chronology and medical care by pre-hospital then hospital neurology intensive care, MRI diagnosis validation, cerebral infarction area. For controls : patient characteristics, history.
Patient characteristics, clinical signsDay 2patients characteristics, clinical signs and medical care by hospital neurology intensive care.
Depression scaleDay 2Interview with the patient, or a patient closely related, or a physician. Scale for depression scores (simplified depression scale from Whooley 2006), concerning the 2 weeks before stroke
Impulsivity scaleDay 2Interview with the patient, or a patient closely related, or a physician. Scale for impulsivity scores ( Barratt Impulsiveness scale), concerning the 2 weeks before stroke

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026