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Neuroactive Steroids in Acute Ischemic Stroke (Cortisol)

7 augustus 2017 bijgewerkt door: Sebastian Casas, Hospital Militar Central, Argentina

Changes in Plasma Cortisol, Brain-derived Neurotrophic Factor, and Nitrites in Patients With Acute Ischemic Stroke

Acute ischemic stroke (AIS) represents an economical challenge for health systems all over the globe. Despite increasing knowledge of the pathophysiology of AIS, there is no satisfactory treatment to revert the resulting brain damage. Changes of neuroactive steroids have been found in different neurological diseases. In this regard, the investigators have previously demonstrated that old patients with AIS show changes of plasma cortisol and estradiol concentrations, in that increased steroid levels are associated with a deterioration of neurological status and a worse cognitive decline. The present study assessed in patients with AIS if changes of behavior, brain-derived neurotrophic factor (BDNF) and nitrites (NO-2) (nitric oxide soluble metabolite) bear a relationship with the degree of hypercortisolism. To this purpose, the investigators recruited patients hospitalized at the Central Military Hospital emergency room within the first 24 hours of AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40 AIS patients, including men and women. The neurological condition was assessed using the NIHSS and the cognitive status with the Montreal Cognitive Assessment (MoCA test). The emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively.

Studie Overzicht

Toestand

Voltooid

Interventie / Behandeling

Gedetailleerde beschrijving

Acute Ischemic Stroke (AIS) is one of the main causes of functional deterioration all over the world. Thus, 26% of patients older than 65 years still show limitations of daily activities 6 months after AIS, and 46% of these patients present cognitive deficiency of variable severity. AIS impose a burden on the way of living of patients and their families' in which depression emerges as a frequent neuropsychiatric disorder after the ischemic event. However, the occurrence of depression and other functional abnormalities on the first day following AIS is largely unknown. Neuroactive steroids have the capability to modulate in a positive or negative way the function of the nervous system. Changes in neuroactive steroid concentrations in plasma and nervous system have been described in degenerative diseases (Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis), autoimmune diseases (multiple sclerosis), epilepsy, and psychiatric disorders (depression and schizophrenia). In vulnerable regions such as the hippocampus and prefrontal cortex, high cortisol exposure damages the pyramidal neurons, decreases neurogenesis and impairs memory and learning. In a previous report, the investigators have demonstrated that old patients with AIS show changes in the plasma levels of cortisol and estradiol, which associate with low cognition, worse neurological status, and poor functional performance. The present report investigated changes of cortisol, brain-derived neurotrophic factor (BDNF) and nitrites (NO-2, nitric oxide soluble metabolites) after AIS. BDNF is a neurotrophin classically associated with learning and memory and negatively modulated by glucocorticoids, old age, and neurodegenerative diseases. In plasma, platelets are the major source of peripheral BDNF and levels of this neurotrophin are decreased in Alzheimer´s disease and depression. These disorders also show hypercortisolism and changes of cortisol dynamics suggesting that steroids, neurotrophins, and behavioral deficits may be functionally related. Regarding nitrites, cortisol treatment of human subjects significantly reduced plasma nitrate/nitrite concentrations. Therefore, considering that opposite changes occur in cortisol vs. BDNF and nitrites, the investigators aimed to determine in acute AIS patients (a) changes in plasma cortisol; (b) development of clinical, behavioral and functional deficits; (c) changes in plasma BDNF and nitrites, which may predict a neurotoxic effect of the excess cortisol in the ischemic nervous system.

Studietype

Observationeel

Inschrijving (Werkelijk)

40

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

60 jaar tot 90 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

The subjects were between 60 and 90 years old, and were recruited randomly and distributed in two experimental groups: 1) a control group composed of subjects without physical or psychiatric disease, 2) an AIS group composed of subjects within the first 24 hours of the neurovascular event. The individuals were distributed in such a way that each experimental group contained 10 men and 10 women. Table 1 show the inclusion and exclusion criteria used for the AIS group.

Beschrijving

Inclusion Criteria:

  • Age between 60 and 90 years.
  • Agreeing to participate in the study.
  • Acute Ischemic Stroke of anterior vascular territory and/or posterior vascular territory whithin 24 hours of onset.
  • Nine or more points in the Glasgow Coma Scale.
  • Female patients in menopause.
  • Patients without cognitive impairment before AIS according to family reference.
  • Acceptance of the next of kin proxy in case the participant has sensory impairment.

Exclusion Criteria:

  • Age <60 or > 90 years.
  • Hemorrhagic Stroke.
  • Transient ischemic attack (TIA).
  • Acute Ischemic Stroke after 24 hours of onset.
  • Hormonal replacement therapy.
  • Immunosuppressive therapy in the last month before AIS (example corticosteroids).
  • Acute infection (Example, pneumonia, urinary tract infection).
  • Diagnosis of oncologic disease in the last month before AIS.
  • Diagnosis of endocrinologic disease in the last month before AIS.
  • Acute or long-term psychiatric illness.
  • No agreement to participate in the study.
  • Eight or less points in the Glasgow Coma Scale.
  • Female patients with menstrual cycle or in the perimenopause.
  • Patients with kidney or hepatic illness.
  • Patients with cognitive impairment before AIS.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Observatiemodellen: Case-control
  • Tijdsperspectieven: Prospectief

Cohorten en interventies

Groep / Cohort
Interventie / Behandeling
Control group
A control group composed of subjects without physical or psychiatric disease.
We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.
Andere namen:
  • Plasma cortisol levels quantification
  • Plasma nitrites levels quantification
  • Plasma Brain Derived Neurotrophic Factor quantification
Acute Ischemic Stroke group
An AIS group composed of subjects within the first 24 hours of the neurovascular event.
We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.
Andere namen:
  • Plasma cortisol levels quantification
  • Plasma nitrites levels quantification
  • Plasma Brain Derived Neurotrophic Factor quantification

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Neurological déficit
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
The neurological state during AIS was quantified by the National Institute of Health stroke scale at the time of hospitalization (NIHSS,available at http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf
Into 24 hours of Acute Ischemic Stroke

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Cognition
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
The cognitive test used was the Montreal Cognitive Assessment (MoCA test).
Into 24 hours of Acute Ischemic Stroke
Emotional state
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
Patients with AIS were evaluated on the Montgomery-Asberg depression scale (MADRS)
Into 24 hours of Acute Ischemic Stroke
Functional dependency of daily life activities
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
The functional state of the AIS patients was assessed by the modified Rankin scale at the time of entering the admission floor.
Into 24 hours of Acute Ischemic Stroke
Cortisol
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
Plasma cortisol concentration was determined by chemiluminescent microparticle immunoassay (CMIA), using Team Architect i1000, Abbott Laboratories, Middletown, USA.
Into 24 hours of Acute Ischemic Stroke
Quantification of nitrites concentration (NO-2)
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
Levels of NO-2, nitric oxide soluble metabolite (ON.) in water, were measured spectrophotometrically at 543 nm absorbance by the Griess reactio
Into 24 hours of Acute Ischemic Stroke
BDNF quantification in plasma
Tijdsspanne: Into 24 hours of Acute Ischemic Stroke
Plasma BDNF concentration was measured by enzyme-linked immunosorbent assay (ELISA)
Into 24 hours of Acute Ischemic Stroke

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Hoofdonderzoeker: Sebastian M Casas, Ph.D., MD., Hospital Militar Central Cir My ¨Dr. Cosme Argerich¨

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 april 2016

Primaire voltooiing (Werkelijk)

1 december 2016

Studie voltooiing (Werkelijk)

1 december 2016

Studieregistratiedata

Eerst ingediend

2 augustus 2017

Eerst ingediend dat voldeed aan de QC-criteria

7 augustus 2017

Eerst geplaatst (Werkelijk)

8 augustus 2017

Updates van studierecords

Laatste update geplaatst (Werkelijk)

8 augustus 2017

Laatste update ingediend die voldeed aan QC-criteria

7 augustus 2017

Laatst geverifieerd

1 augustus 2017

Meer informatie

Termen gerelateerd aan deze studie

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

Nee

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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