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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Infarction
• Intervention / Treatment: Other: Usual care patients in neurology department; Biological: blood and urines sampling; Procedure: Psychiatric evaluation

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Le Chesnay, France, 78150
    • Centre Hospitalier De Versailles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients presenting cerebral infarction; no intervention of health product administration,	Other: Usual care patients in neurology department; patients characteristics, history, clinical signs chronology and usual medical care by the emergency units, cerebral infarction area; Biological: blood and urines sampling; Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations; Procedure: Psychiatric evaluation; depression scale, impulsivity scale, hostility scale , tobacco consumption questioning
Other: Historical controls; no intervention of health product administration, patients characteristics, history, matched with patients for age, gender, tobacco consumption and season of inclusion, free of neurologic or psychiatric disease or psychotropic medications or medications known to impact on serotonin	Biological: blood and urines sampling; Collection samples for biochemical determinations of serotonin pathway and kynurenine pathway parameters determinations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of serotonin pathway parameters concentrations in blood and urine samples	platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods.	Day 1
Measure of serotonin pathway parameters in blood samples	Blood 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)	Day 1
Measure of serotonin pathway parameters in blood and urine samples	platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods	Day 2
Measure of serotonin pathway parameters in blood and urine samples	platelet serotonin (nM), plasma serotonin (nM), urine serotonin (nM) , plasma 5-HIAA (nM) , urine 5-HIAA (nM) concentrations using three different HPLC systems and methods	Month 3
Measure of kynurenin pathway parameters in blood samples	The 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 .	Day 1
Measure of kynurenin pathway parameters in blood samples	The 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 .	Day 2
Measure of kynurenin pathway parameters in blood samples	The 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 .	Month 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient characteristics, history, clinical signs chronology	For 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.	Day 1
Patient characteristics, clinical signs	patients characteristics, clinical signs and medical care by hospital neurology intensive care.	Day 2
Patient characteristics, clinical signs	Patients characteristics, clinical signs and medical care. .	Month 3
Depression scale	Interview 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	Day 2
Impulsivity scale	Interview with the patient, or a patient closely related, or a physician. Scale for impulsivity scores ( Barratt Impulsiveness scale), concerning the 2 weeks before stroke	Day 2

Collaborators and Investigators

• Sponsor: Versailles Hospital
• Investigators: Principal Investigator: Odile SPREUX-VAROQUAUX, PhD, Pharmacology, Versailles Hospital and Versailles University; Study Director: Fernando PICO, Neurology Department head, Versailles Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 16, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 15, 2016

Study Record Updates

• Last Update Posted (Estimate): November 17, 2016
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Brain Infarction; Infarction; Cerebral Infarction
• Other Study ID Numbers: P11/25_AVC-TSK