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

Cerebral Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02963545
• Other study ID #: P11/25_AVC-TSK
• Status: Completed
• Phase: N/A
• First received: September 16, 2016
• Last updated: November 16, 2016
• Start date: October 2012
• Est. completion date: May 2016

Study information

• Verified date: November 2016
• Source: Versailles Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: May 2016
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cerebral Infarction
• Infarction

Intervention

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

Locations

Country	Name	City	State
France	Centre Hospitalier de Versailles	Le Chesnay

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Other	Patient characteristics, clinical signs	patients characteristics, clinical signs and medical care by hospital neurology intensive care.	Day 2	Yes
Other	Patient characteristics, clinical signs	Patients characteristics, clinical signs and medical care.	Month 3	Yes
Other	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	Yes
Other	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes