Neuroactive Steroids in Acute Ischemic Stroke

NCT03242304 | Completed DMC

• 1 other identifier: act No. 393 of Nov 11, 2015
• Study Type: observational
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Ischemic Stroke; Cortisol; Hypersecretion

Outcome Measures

Primary Outcomes (1)

• Neurological déficit

  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

Secondary Outcomes (6)

• Cognition

  Into 24 hours of Acute Ischemic Stroke

• Emotional state

  Into 24 hours of Acute Ischemic Stroke

• Functional dependency of daily life activities

  Into 24 hours of Acute Ischemic Stroke

• Cortisol

  Into 24 hours of Acute Ischemic Stroke

• Quantification of nitrites concentration (NO-2)

  Into 24 hours of Acute Ischemic Stroke

Study Arms (2)

Control group

A control group composed of subjects without physical or psychiatric disease.

Other: Behavioral tests

Acute Ischemic Stroke group

An AIS group composed of subjects within the first 24 hours of the neurovascular event.

Other: Behavioral tests

Interventions

Behavioral tests OTHER

We observed relationship between plasma levels of cortisol and neurological, cognitive, functional and emotional outcomes in patients with acute ischemic stroke.

Also known as: Plasma cortisol levels quantification, Plasma nitrites levels quantification, Plasma Brain Derived Neurotrophic Factor quantification

Acute Ischemic Stroke group; Control group

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Militar Central, Argentina: lead

Related Publications (6)

• 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.

  PMID: 27813048 RESULT

• 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.

  PMID: 25918669 RESULT

• 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.

  PMID: 23561326 RESULT

• 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.

  PMID: 22155686 RESULT

• 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.

  PMID: 21820473 RESULT

• 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.

  PMID: 21689676 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Behavior Rating Scale

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Sebastian M Casas, Ph.D., MD.

  Hospital Militar Central Cir My ¨Dr. Cosme Argerich¨

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D, M.D.

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 8, 2017
• Study Start: April 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 8, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share