- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT03242304
Neuroactive Steroids in Acute Ischemic Stroke (Cortisol)
7 de agosto de 2017 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
De observación
Inscripción (Actual)
40
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
60 años a 90 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra de probabilidad
Población de estudio
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.
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: Control de caso
- Perspectivas temporales: Futuro
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
---|---|
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.
Otros nombres:
|
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.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Neurological déficit
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Cognition
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Sebastian M Casas, Ph.D., MD., Hospital Militar Central Cir My ¨Dr. Cosme Argerich¨
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Casas S, Giuliani F, Cremaschi F, Yunes R, Cabrera R. Neuromodulatory effect of progesterone on the dopaminergic, glutamatergic, and GABAergic activities in a male rat model of Parkinson's disease. Neurol Res. 2013 Sep;35(7):719-25. doi: 10.1179/1743132812Y.0000000142. Epub 2013 Mar 5.
- Yunes R, Casas S, Gaglio E, Cabrera R. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3 alpha -Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of GABAA Receptors Involvement. Parkinsons Dis. 2015;2015:431690. doi: 10.1155/2015/431690. Epub 2015 Mar 31.
- Escudero C, Casas S, Giuliani F, Bazzocchini V, Garcia S, Yunes R, Cabrera R. Allopregnanolone prevents memory impairment: effect on mRNA expression and enzymatic activity of hippocampal 3-alpha hydroxysteroid oxide-reductase. Brain Res Bull. 2012 Feb 10;87(2-3):280-5. doi: 10.1016/j.brainresbull.2011.11.019. Epub 2011 Dec 6. Erratum In: Brain Res Bull. 2012 Nov 1;89(3-4):150.
- Casas S, Garcia S, Cabrera R, Nanfaro F, Escudero C, Yunes R. Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats. Pharmacol Biochem Behav. 2011 Oct;99(4):614-8. doi: 10.1016/j.pbb.2011.06.012. Epub 2011 Jun 15.
- Casas S, Gonzalez Deniselle MC, Gargiulo-Monachelli GM, Perez AF, Tourreilles M, Mattiazzi M, Ojeda C, Lotero Polesel D, De Nicola AF. Neuroactive Steroids in Acute Ischemic Stroke: Association with Cognitive, Functional, and Neurological Outcomes. Horm Metab Res. 2017 Jan;49(1):16-22. doi: 10.1055/s-0042-119201. Epub 2016 Nov 3.
- Ghersi MS, Casas SM, Escudero C, Carlini VP, Buteler F, Cabrera RJ, Schioth HB, de Barioglio SR. Ghrelin inhibited serotonin release from hippocampal slices. Peptides. 2011 Nov;32(11):2367-71. doi: 10.1016/j.peptides.2011.07.015. Epub 2011 Jul 27.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de abril de 2016
Finalización primaria (Actual)
1 de diciembre de 2016
Finalización del estudio (Actual)
1 de diciembre de 2016
Fechas de registro del estudio
Enviado por primera vez
2 de agosto de 2017
Primero enviado que cumplió con los criterios de control de calidad
7 de agosto de 2017
Publicado por primera vez (Actual)
8 de agosto de 2017
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
8 de agosto de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
7 de agosto de 2017
Última verificación
1 de agosto de 2017
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Necrosis
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Trastornos cerebrovasculares
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Isquemia cerebral
- Infarto
- Infarto cerebral
- Carrera
- Accidente cerebrovascular isquémico
- Isquemia
- Infarto cerebral
- Agentes antiinflamatorios
- Hidrocortisona
Otros números de identificación del estudio
- act No. 393 of Nov 11, 2015
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
No
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Behavioral tests
-
Bernadetta IzydorczykJagiellonian UniversityTerminadoEstrés Psicológico | Estrés mental | Problema de salud mental | Problema relacionado con el estrés | Bienestar psicológico | Trauma acumulativoPolonia
-
University of OxfordOxford University Hospitals NHS TrustDesconocidoSíntomas de comportamientoReino Unido
-
Centre Hospitalier Universitaire de BesanconUniversity of Franche-ComtéReclutamiento
-
Assistance Publique - Hôpitaux de ParisAún no reclutandoPérdida de la audición | Función cognitiva | Función ejecutiva | Función vestibularFrancia
-
University of LiegeReclutamientoCirugía | Hombro | Volver al deporteBélgica
-
Square2 Systems, Inc.National Institute on Drug Abuse (NIDA)ReclutamientoTrastornos relacionados con sustancias | Trastornos por uso de sustanciasEstados Unidos
-
Virginia Polytechnic Institute and State UniversityCarilion Clinic; Thomas Jefferson University; Drexel University; Mazzoni Health Center y otros colaboradoresActivo, no reclutandoSuicidio | Compromiso, PacienteEstados Unidos
-
Network for Engineering and Economics Research...TerminadoAnticoncepción | Anemia por deficiencia de hierro del embarazo | Cuidado prenatal | Atención posnatalIndia