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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02963545
First Posted: November 15, 2016
Last Update Posted: November 17, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Odile VAROQUAUX, Versailles Hospital
  Purpose

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.


Condition Intervention
Cerebral Infarction Other: Usual care patients in neurology department Biological: blood and urines sampling Procedure: Psychiatric evaluation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Odile VAROQUAUX, Versailles Hospital:

Primary Outcome Measures:
  • Measure of serotonin pathway parameters concentrations in blood and urine samples [ Time Frame: Day 1 ]
    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.

  • Measure of serotonin pathway parameters in blood samples [ Time Frame: Day 1 ]
    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)

  • Measure of serotonin pathway parameters in blood and urine samples [ Time Frame: Day 2 ]
    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

  • Measure of serotonin pathway parameters in blood and urine samples [ Time Frame: Month 3 ]
    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

  • Measure of kynurenin pathway parameters in blood samples [ Time Frame: Day 1 ]
    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 .

  • Measure of kynurenin pathway parameters in blood samples [ Time Frame: Day 2 ]
    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 .

  • Measure of kynurenin pathway parameters in blood samples [ Time Frame: Month 3 ]
    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 .


Other Outcome Measures:
  • Patient characteristics, history, clinical signs chronology [ Time Frame: Day 1 ]

    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.


  • Patient characteristics, clinical signs [ Time Frame: Day 2 ]
    patients characteristics, clinical signs and medical care by hospital neurology intensive care.

  • Patient characteristics, clinical signs [ Time Frame: Month 3 ]

    Patients characteristics, clinical signs and medical care.


  • Depression scale [ Time Frame: Day 2 ]
    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

  • Impulsivity scale [ Time Frame: Day 2 ]
    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


Enrollment: 28
Study Start Date: October 2012
Study Completion Date: May 2016
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02963545


Locations
France
Centre Hospitalier de Versailles
Le Chesnay, France, 78150
Sponsors and Collaborators
Versailles Hospital
Investigators
Principal Investigator: Odile SPREUX-VAROQUAUX, PhD Pharmacology, Versailles Hospital and Versailles University
Study Director: Fernando PICO, Neurology Department head Versailles Hospital
  More Information

Responsible Party: Odile VAROQUAUX, Investigator coordinator, Versailles Hospital
ClinicalTrials.gov Identifier: NCT02963545     History of Changes
Other Study ID Numbers: P11/25_AVC-TSK
First Submitted: September 16, 2016
First Posted: November 15, 2016
Last Update Posted: November 17, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Infarction
Cerebral Infarction
Ischemia
Pathologic Processes
Necrosis
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Stroke
Vascular Diseases
Cardiovascular Diseases
Serotonin
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs