Cognitive Improvement After Carotid Stenting in Hyperbaric Oxygen Therapy Trial

Study Overview
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Brief Summary
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The purpose of CARE-HBOT study is to evaluate whether patients with symptomatic severe carotid artery stenosis with cognitive impairment who underwent hyperbaric oxygen therapy plus standard medical treatment after stent implantation could improve their cognitive function compared with those who underwent standard postoperative medical treatment.

Detailed Description
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This study is a prospective, multi-center, 1:1 randomized trial. In patients with symptomatic severe carotid artery stenosis with cognitive impairment underwent stent implantation, whether hyperbaric oxygen therapy plus standard medical treatment after stenting could improve their cognitive function compared with those who underwent standard postoperative medical treatment will be studied. Primary endpoint: Cognitive level at 6 months of follow up.

Official Title
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Cognitive Improvement After cARotid stEnting in HyperBaric Oxygen Therapy Trial (CARE-HBOT)

Conditions
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Carotid Stenosis, Cognitive Impairment, Hyperbaric Oxygen Therapy, Stent Implantation

Intervention / Treatment
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* Procedure: Hyperbaric oxygen therapy
* Drug: Standard medical treatment
* Behavioral: Risk factor management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 75 years Ischemic stroke or transient ischemic attack (TIA) occurred within 30 days before endovascular stent treatment National Institute of Health stroke scale (NIHSS) ≤3 Culprit vessel was the common carotid artery or extracranial internal carotid artery, involving or not involving the external carotid artery The degree of culprit arterial stenosis is 70-99 % ; based on Digital subtraction angiography (DSA) (According to North American Symptomatic Carotid Endarterectomy Trial (NASCET) method) The diameter of the target vessel between 4.0 mm - 9.0 mm Mini-mental State Examination (MMSE) score : education level-middle school ≤ 24; education level-high school ≤ 20 ; education level-college ≤ 17 Baseline modified Rankin Scale (mRS) score ≤ 3 Patient understands the purpose and requirements of the study, and has provided informed consent Exclusion Criteria: Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion Serious perioperative complications affecting subsequent hyperbaric oxygen therapy (such as cerebral hemorrhage, disabling stroke, etc.) Any history of brain parenchymal or subarachnoid, subdural or extradural haemorrhage in the past 12 months Hemorrhagic transformation after ischemic stroke within 60 days before enrollment Intracranial artery stenosis caused by non-atherosclerotic lesions, including: arterial dissection, Moyamoya disease, vasculitis disease, herpes zoster, varicella-zoster or other viral vascular diseases, neurosyphilis, any other intracranial infections, any intracranial stenosis related to cerebrospinal fluid cells, radiation-induced vascular disease, fibromuscular dysplasia, sickle cell disease, neurofibromatosis, central nervous system benign vascular disease, postpartum vascular disease, suspected vasospasm, suspicious embolism recanalization, etc Nervous system diseases in the past two years, characterized by transient or fixed neurological deficits (such as partial or secondary generalized seizures of epilepsy, complex or classic migraine, tumor or other intracranial space-occupying lesions, subdural hematoma, brain contusion or other post-traumatic lesions, intracranial infection, demyelinating diseases, intracranial hemorrhage, etc.), which cannot be distinguished from cerebral infarction History of stenting of an intracranial or extracranial artery Presence of any unequivocal cardiac source of embolism Chronic atrial fibrillation; paroxysmal atrial fibrillation or paroxysmal atrial fibrillation in the past 6 months, or a history of paroxysmal atrial fibrillation, requiring long-term anticoagulation Myocardial infarction in the past 30 days Combined with intracranial tumor, aneurysm or intracranial arteriovenous malformation Cannot tolerate dual antiplatelet therapy due to known diseases (such as gastrointestinal bleeding) Contraindications to heparin, aspirin, clopidogrel, ticagrelor, anesthesia, or contrast agents Hemoglobin<100g/L, platelet count <100×109/L, international normalized ratio (INR)>1.5, or heparin-related thrombocytopenia or uncorrectable factors leading to bleeding Not suitable for vessel angiography or endovascular interventional therapy (such as morbid obesity; serious vascular tortuosity that hinders the safe introduction of the guiding catheter) Severe hepatic and renal dysfunction Major surgery within the past 30 days or planned within 90 days Renal artery, iliac artery, and coronary artery requiring simultaneous intervention Life expectancy <1 year Pregnant or lactating women Cognitive assessment and follow-up could not be completed due to factors such as severe aphasia, neuropsychological illness or mental illness or dysarthria and inability to communicate History of drug or alcohol abuse, head trauma or central nervous system infection; current use of drugs that affect cognition Combined with diseases that are not suitable for hyperbaric oxygen therapy (such as untreated pneumothorax, uncontrolled epilepsy, claustrophobia, angle-closure glaucoma, cavitary pulmonary tuberculosis, etc.) Enrollment in another study that would conflict with the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric oxygen therapy plus standard medical treatment<br>Patients will receive hyperbaric oxygen therapy plus standard medical treatment after stenting | Procedure: Hyperbaric oxygen therapy<br>* Hyperbaric oxygen therapy for 30 times within 50 days<br>Drug: Standard medical treatment<br>* Standard medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 3 months after stenting). Other Name: Dual antiplatelet therapy for 3 months<br>Behavioral: Risk factor management<br>* Management of risk factors including hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise<br>|
| Active Comparator: Standard medical treatment<br>Patients will receive standard medical treatment after stenting | Drug: Standard medical treatment<br>* Standard medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 3 months after stenting). Other Name: Dual antiplatelet therapy for 3 months<br>Behavioral: Risk factor management<br>* Management of risk factors including hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MoCA) | Chinese version of Montreal Cognitive Assessment (MoCA) will be use to assess the cognitive level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 30. Higher scores mean a better outcome. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State Examination (MMSE) | Chinese version of MMSE will be use to assess the cognitive level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 30. Higher scores mean a better outcome. | 6 months | 
| Auditory Verbal Learning Test (AVLT) | Chinese version of AVLT will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 12. Higher scores mean a better outcome. | 6 months | 
| Symbol Digital Modalities Test (SDMT) | Chinese version of SDMT will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 90. Higher scores mean a better outcome. | 6 months | 
| Digit Span Test (DST) | Chinese version of DST will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 22. Higher scores mean a better outcome. | 6 months | 
| Stroop Color-Word Test (Stroop) | Chinese version of Stroop will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 50. Higher scores mean a better outcome. | 6 months | 
| Trail Making Test (TMT) | Chinese version of TMT will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. Recording time consumption. Shorter time consumptions mean a better outcome. | 6 months | 
| Boston Naming Test (BNT) | Chinese version of BNT will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 30. Higher scores mean a better outcome. | 6 months | 
| Verbal Fluence Test (VFT) | Chinese version of VFT will be use to assess the cognitive function domain level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. Record the number of correct phrases. Higher scores mean a better outcome. | 6 months | 
| Hamilton Anxiety Scale (HAMA) | Chinese version of HAMA will be use to assess the anxiety level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 64. Higher scores mean a better outcome. | 6 months | 
| Hamilton Depression Scale (HAMD) | Chinese version of HAMD will be use to assess the depression level of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 96. Higher scores mean a better outcome. | 6 months | 
| Pittsburgh Sleep Quality Index (PSQI) | Chinese version of PSQI will be use to assess the sleep quality of the hyperbaric oxygen therapy group (HBOT group) and the control group at 6 months after procedure. The minimum value is 0 and the maximum value is 27. Higher scores mean a better outcome. | 6 months |