Neuroactive Steroids in Acute Ischemic Stroke

NCT02914106 | Completed DMC

• 1 other identifier: (C.I.R.E.C.) Act N ° 308
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Despite several scientific and technological advances, there is no single neuroprotective treatment that can reverse the brain damage after acute ischemic stroke (AIS). Neuroactive steroids are cholesterol-derived hormones that have the ability to modulate the normal and pathologic nervous system employing genomic and non genomic mechanisms. In this work, we first investigated if AIS affects the plasma concentration of five neuroactive steroids (cortisol, estradiol, progesterone, testosterone and 3-alpha androstenediol glucuronide). Second, we studied if levels of circulating steroids associate with neurological, cognitive and functional outcome in a cohort of 60 to 90 year-old male and female patients with AIS. For this purpose, we recruited patients who were hospitalized at the Emergency Room of the Central Military Hospital within the first 24 hours after stroke onset. We designed two experimental groups, each one composed of 30 control subjects and 30 AIS patients, both males and females. The assessment of neurological deficit was performed with the NIHSS and the tests used for the functional and cognitive status were: (1) modified Rankin Scale; (2) Photo test and (3) abbreviated Pfeiffer's mental status questionnaire.

Conditions

Ischemic Stroke

Keywords

Neuroactive steroids; Acute Ischemic Stroke; Patients

Outcome Measures

Primary Outcomes (1)

• Neurological impairment by the Institute of health stroke scale

  The assessment of neurologic status during the AIS was carried out with 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)

• Cognitive impairment by photos Test.

  Into 24 hours of Acute Ischemic Stroke

• Cognitive impairment by Pfeiffer Test

  Into 24 hours of Acute Ischemic Stroke

• Functional dependence for daily activities by Rankin Scale

  Into 24 hours of Acute Ischemic Stroke

• Quantitation of neuroactive steroids in plasma by electrochemiluminescence immunoassay (ECLIA).

  Into 24 hours of Acute Ischemic Stroke

• Quantitation of neuroactive steroids in plasma by an immunoassay chemiluminescent microparticle (CMIA).

  Into 24 hours of Acute Ischemic Stroke

Study Arms (2)

Control group

Sixty-90 year-old subjects were randomly selected and distributed in two experimental groups: 1) a control group, involving subjects without physical or psychiatric illness, and 2) an Acute Ischemic Stroke group (AIS group).

Other: Observational Study

Acute Ischemic Stroke group

Patients with diagnosis of AIS within the 24 hours of their neurovascular event.

Other: Observational Study

Interventions

Observational Study OTHER

Patients were diagnosed for AIS by a certified neurologist at the Emergency Room of the Central Military Hospital. Neurological, cognitive and functional status were determined by NIHSS score, Photo test, Pfeiffer mental status score and by modified Rankin score respectively. A sample of venous blood was withdrawn in the early morning (07 to 09 AM) after assessment of neurological and cognitive status.

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

Sixty-90 year-old subjects were randomly selected and distributed in two experimental groups: 1) a control group, involving subjects without physical or psychiatric illness, and 2) an AIS group, consisting of: patients with diagnosis of AIS within the 24 hours of their neurovascular event. Subjects were distributed between groups so that each group contained 30 patients (15 women and 15 men).

You may qualify if:

• Age between 60 and 90 years.
• Agreeing to participate in the study.
• Fourteen or more points in the Glasgow Coma Scale.
• Female control in menopause.
• Control subjects without cognitive impairment according to certified neurologist.

You may not qualify if:

• Age \<60 or \> 90 years.
• Hormonal replacement therapy.
• Immunossupresive therapy in the last month (Example corticosteroids).
• Acute infection (Example, pneumonia, urinary tract infection).
• Diagnosis of oncologic disease in the last month.
• Diagnosis of endocrinologic disease in the last month.
• Acute or long-term psychiatric illness.
• No agreement to participate in the study
• Thirteen 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.

Sponsors & Collaborators

• Hospital Militar Central, Argentina: lead

Related Publications (5)

• 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 BACKGROUND

• 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

• 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

• 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

• 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

Observation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Sebastian Casas, PhD

  Central Military Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 26, 2016
• Study Start: June 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 26, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share