Iron, Alpha-Synuclein, and Lymphocyte-activation Gene-3 in Ischemic Stroke

• Sponsor: Aswan University Hospital (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05748587
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Anticipated Duration (Months): 12
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This observational study aims to detect levels of iron, alpha-synuclein, and soluble lymphocyte activation gene 3 in acute ischemic stroke patients. And to see expressions of iron, alpha-synuclein, and lymphocyte activation gene 3 in the brain tissue of ischemic rats.

The main questions it aims to answer are:

• Is there an association between iron and alpha-synuclein accumulation in ischemic stroke?

• Is there any change in soluble lymphocyte activation gene levels in ischemic stroke and if these levels are related to stroke severity and infarction size? . Can soluble lymphocyte activation gene levels be used as an early biomarker to diagnose ischemic stroke?

Condition or Disease	Intervention/Treatment	Phase
Brain Ischemia	Diagnostic Test: Serum Iron; Diagnostic Test: RBCs Alpha-synuclein; Diagnostic Test: Serum Soluble lymphocyte activation gene; Radiation: Brain computed tomography; Diagnostic Test: Brain Iron; Diagnostic Test: Brain Alpha-synuclein; Diagnostic Test: Brain lymphocyte activation gene; Drug: Deferoxamine

Study Design

• Study Type: Observational
• Anticipated Enrollment: 48 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Role of Iron, Alpha-Synuclein, and Lymphocyte-activation Gene-3 in the Pathophysiology of Ischemic Stroke in Human and Albino Rats
• Anticipated Study Start Date: Apr 1, 2023
• Anticipated Primary Completion Date: Mar 1, 2024
• Anticipated Study Completion Date: Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Control 24 healthy age and sex-matched controls	Diagnostic Test: Serum Iron; Serum iron levels in study groups; Diagnostic Test: RBCs Alpha-synuclein; α-syn levels in RBCs; Other Names: α-syn ; Diagnostic Test: Serum Soluble lymphocyte activation gene; sLAG-3 in the serum of study groups; Other Names: sLAG-3 ; Radiation: Brain computed tomography; Brain CT of patients after admission; Other Names: CT
Patients with acute Ischemic stroke 24 patients between 50-70 years having neurological symptoms of acute ischemic stroke will be included. Patients with acute hemorrhagic stroke, Parkinson's disease, dementia, Alzheimer's disease, malignancy, and central nervous system infection will be excluded.	Diagnostic Test: Serum Iron; Serum iron levels in study groups; Diagnostic Test: RBCs Alpha-synuclein; α-syn levels in RBCs; Other Names: α-syn ; Diagnostic Test: Serum Soluble lymphocyte activation gene; sLAG-3 in the serum of study groups; Other Names: sLAG-3 ; Radiation: Brain computed tomography; Brain CT of patients after admission; Other Names: CT
Control rats 8 rats will be subjected to a Sham operation and will be injected intramuscularly immediately after the operation with an equivalent 0.9% saline solution. After 24 hours they will be sacrificed.	Diagnostic Test: Brain Iron; Iron in brain homogenate of rats; Diagnostic Test: Brain Alpha-synuclein; α-syn expression in rat's brain; Other Names: α-syn ; Diagnostic Test: Brain lymphocyte activation gene; LAG-3 expression in rat's brain; Other Names: LAG-3
Rats with ischemic stroke 8 rats will be subjected to bilateral common carotid artery occlusion (CCAO) for 30 minutes and will be injected intramuscularly immediately after removing the occlusion with an equivalent 0.9% saline solution. They will be sacrificed after 24 hours of reperfusion.	Diagnostic Test: Brain Iron; Iron in brain homogenate of rats; Diagnostic Test: Brain Alpha-synuclein; α-syn expression in rat's brain; Other Names: α-syn ; Diagnostic Test: Brain lymphocyte activation gene; LAG-3 expression in rat's brain; Other Names: LAG-3
Rats with ischemic stroke + deferoxamine 8 rats will be subjected to bilateral CCAO for 30 minutes and will be injected intramuscularly immediately after removing the occlusion with deferoxamine (200 mg/kg), They will be sacrificed after 24 hours of reperfusion.	Diagnostic Test: Brain Iron; Iron in brain homogenate of rats; Diagnostic Test: Brain Alpha-synuclein; α-syn expression in rat's brain; Other Names: α-syn ; Diagnostic Test: Brain lymphocyte activation gene; LAG-3 expression in rat's brain; Other Names: LAG-3 ; Drug: Deferoxamine; intramuscular deferoxamine (200 mg/kg) injection to rats

Outcome Measures

Primary Outcome Measures

1. Iron levels [6 months]

   Serum iron levels in ischemic patients and control

2. Alpha-synuclein levels [6 months]

   Alpha-synuclein levels in RBCs in ischemic patients and control

3. Levels of Soluble lymphocyte activation gene-3 [6 months]

   Serum soluble lymphocyte activation gene-3 in ischemic patients and control

4. levels of iron, alpha-synuclein, and soluble lymphocyte activation in relation to stroke severity and infarction size [6 months]

   stroke severity will be evaluated by the National Institutes of Health Stroke Scale (NIHSS) and size of infarction will be detected by brain CT

5. Iron levels in brain of rats [2 months]

   Iron levels in brain homogenate of rats in the three rat groups

6. Levels of Alpha-synuclein expression in brain of rats [2 months]

   Alpha-synuclein expression in brain of rats in different groups

7. Levels of Lymphocyte activation gene-3 expression in brain of rats [2 months]

   lymphocyte activation gene-3 expression in brain of rats in different groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients at the age between 50-70 years.

2. Patients having neurological symptoms of acute ischemic stroke.

Exclusion Criteria:

1. Patients with acute hemorrhagic stroke.

2. Patients with Parkinson's disease (PD).

3. Patients with dementia, and Alzheimer's disease.

4. Patients with any type of malignancy.

5. Patients with central nervous system infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aswan University Hospital	Aswan		Egypt	81528

Sponsors and Collaborators

• Aswan University Hospital

Investigators

• Principal Investigator: Asmaa Abdelmageed Muhammed, Aswan University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Malfertheiner K, Stefanova N, Heras-Garvin A. The Concept of alpha-Synuclein Strains and How Different Conformations May Explain Distinct Neurodegenerative Disorders. Front Neurol. 2021 Oct 5;12:737195. doi: 10.3389/fneur.2021.737195. eCollection 2021.
• Wu Q, Wei C, Guo S, Liu J, Xiao H, Wu S, Wu B, Liu M. Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia. IBRO Neurosci Rep. 2022 Jul 3;13:87-95. doi: 10.1016/j.ibneur.2022.06.006. eCollection 2022 Dec.
• Yoon CW, Park HK, Bae EK, Rha JH. Sleep Apnea and Early Neurological Deterioration in Acute Ischemic Stroke. J Stroke Cerebrovasc Dis. 2020 Feb;29(2):104510. doi: 10.1016/j.jstrokecerebrovasdis.2019.104510. Epub 2019 Nov 22.
• Zhao L, Wang H, Xu K, Liu X, He Y. Update on lymphocyte-activation gene 3 (LAG-3) in cancers: from biological properties to clinical applications. Chin Med J (Engl). 2022 May 20;135(10):1203-1212. doi: 10.1097/CM9.0000000000001981.

• Responsible Party: Asmaa Abdel-mageed Muhammed, Lecturer, Aswan University Hospital
• ClinicalTrials.gov Identifier: NCT05748587
• Other Study ID Numbers: sLAG-3 in brain ischemia
• First Posted: Feb 28, 2023
• Last Update Posted: Mar 8, 2023
• Last Verified: Mar 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ischemic Stroke; Brain Ischemia; Ischemia; Iron; Deferoxamine

Study Results

No Results Posted as of Mar 8, 2023