Clinical trial NCT04884555: SH-SS and GSH-GSSG Homeostasis in Post-stroke Patients
Official title: Association of Extracellular Thiol-disulfide and Intracellular Oxidized-reduced Glutathione Homeostasis With Severity and Clinical Prognosis of Post-stroke Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Keywords: stroke
Thiol
Disulphide
Glutathione
Lead sponsor: Abant Izzet Baysal University
Sponsor class: OTHER
First posted: 2021-05-13
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Post-stroke patients group admitted to hospital to take rehablititation and physiotherapy within 1 to 6 months of stroke onset.

Healthy adult volunteers (control) group (\> 18 years of age) with no known disease and no findings on physical examination

Brief summary: In patients undergoing physical therapy after stroke, extracellular thiol-disulfide balance and intracellular oxidized-reduced glutathione balance levels will be monitored. The main objectives of this study are; (1) to determine the differences between thiol-disulfide and GSH-GSSG balances in stroke patients compared to healthy volunteers, (2) to evaluate the relationship of these balances with the severity of stroke, (3) to determine the predictive value of the levels of these balances on clinical prognosis and functional recovery outcomes, and (4) to investigate and to examine the effects of the physical therapy process on these parameters and functional recovery and their relationship with each other.

Detailed description: Stroke is among the most common causes of all deaths and Disability-Adjusted Life Years (DALYs) in the world. There is a close relationship between stroke pathophysiology and post-stroke clinic with oxidative stress. Thiol-disulfide homeostasis systems, which is one of the important extracellular and intracellular oxidative stress markers, showing antioxidant capacity with SH form, and oxidative status with disulfide (SS) form. In this study, we aimed to evaluate the relationship between the clinical outcome of subacute stroke patients and extracellular thiol-disulfide (SH-SS) and intracellular oxidized-reduced glutathione (GSSG-GSH) homeostasis and the comparison of these with healthy volunteers. In addition, the effect of the rehabilitation program on these oxidative stress markers and clinical scores and the predictive value of these oxidative stress parameters on prognosis were also evaluated. The main objectives of this study are; (1) to determine the differences between thiol-disulfide and GSH-GSSG balances in stroke patients compared to healthy volunteers, (2) to evaluate the relationship of these balances with the severity of stroke, (3) to determine the predictive value of the levels of these balances on clinical prognosis and functional recovery outcomes, and (4) to investigate and to examine the effects of the physical therapy process on these parameters and functional recovery and their relationship with each other.

In this study, which is designed as a prospective observational study, patients with subacute stroke who have a stroke for the first time and are admitted to the hospital for the first rehabilitation treatment and healthy volunteers (control group) will be included. The clinical conditions of the patients will be evaluated at the beginning and after the 4-week rehabilitation program at the time of discharge by National Institutes of Health Stroke Scale Scores (NIHSS), modified Rankin Scale (mRS) and Barthel Daily Living Activities Index (BI). Serum and whole blood samples will be obtained from the patient group at the beginning and at discharge, and from the control group. The SH-SS homeostasis parameters (SH, Total SH, SS and SS / SH percent ratio) from serum samples and GSSG-GSH homeostasis parameters (GSH, Total GSH, GSSG and GSSG / GSH percentage ratio) from whole blood samples will be determined. Age, gender, hemiplegic side, type of stroke will be noted. Later, statistical analysis will be conducted.

Eligibility criteria: Inclusion Criteria:

* diagnosis of a first-ever stroke verified by computed tomography (CT) or magnetic resonance imaging (MRI) reports
* admitted to the hospital for standard neurorehabilitation within 1 to 6 months of stroke onset
* healthy individuals (for control group)

Exclusion Criteria:

* significant acute medical illness (e.g., autoimmune disease, infection, tumor, heart failure, renal or liver dysfunction)
* significant acute neurological illness other than stroke (e.g., head trauma, brain abscess, brain tumor, migraine attack, seizure)
* cannot adapt to work
* previous history of neurorehabilitation therapy
* taking the antioxidant supplements

Primary outcomes:
measure: NIHSS Scores
timeFrame: at baseline (pre-treatment)
measure: NIHSS Scores
timeFrame: after 4 weeks of treatment (post-treatment)
measure: mRS
timeFrame: at baseline (pre-treatment)
measure: mRS
timeFrame: after 4 weeks of treatment (post-treatment)
measure: BI
timeFrame: at baseline (pre-treatment)
measure: BI
timeFrame: after 4 weeks of treatment (post-treatment)
Secondary outcomes:
Other outcomes:
Locations:
city: Bolu
country: Turkey
facility: Bolu Abant Izzet Baysal University
Study officials:
affiliation: Abant Izzet Baysal University
name: Tugba Alisik, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989 Jul;20(7):864-70. doi: 10.1161/01.str.20.7.864.
citation: Kucukdeveci AA, Yavuzer G, Tennant A, Suldur N, Sonel B, Arasil T. Adaptation of the modified Barthel Index for use in physical medicine and rehabilitation in Turkey. Scand J Rehabil Med. 2000 Jun;32(2):87-92.
citation: Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials. Stroke. 2017 Jul;48(7):2007-2012. doi: 10.1161/STROKEAHA.117.017866. Epub 2017 Jun 16. No abstract available.
citation: Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014 Dec;47(18):326-32. doi: 10.1016/j.clinbiochem.2014.09.026. Epub 2014 Oct 7.
citation: Alisik, M., Neselioglu, S., & Erel, O. (2019). A colorimetric method to measure oxidized, reduced and total glutathione levels in erythrocytes, Journal of Laboratory Medicine, 43(5), 269-277