The Effect of Huperzine A Injection on Postoperative Cognitive Dysfunction in Patients With Aneurysmal Subarachnoid Hemorrhage: a Pilot Study

Study Overview
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Brief Summary
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Under the premise of basic treatment, to explore the improvement effect of huperzine A injection on short-term and long-term neurocognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage after interventional/surgical treatment.

Detailed Description
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Description: This is a randomized, controlled, single center, exploratory clinical trial. The subjects are divided into surgical treatment group and interventional treatment group. Each group is divided into test group and control group. The test group is given huperzine A injection (0.2mg/dose) every day, intramuscular injection, for a total of 8 days, and basic treatment is given at the same time; The control group was given basic treatment, and did not receive other neurotrophic drugs except basic drugs. This clinical trial is to evaluate the effect of huperzine A injection on the improvement of postoperative cognitive dysfunction in patients with aneurysmal subarachnoid hemorrhage.

Official Title
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The Effect of Huperzine A Injection on Postoperative Cognitive Dysfunction in Patients With Aneurysmal Subarachnoid Hemorrhage: a Pilot Study

Conditions
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Postoperative Cognitive Dysfunction in Patients With Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Huperzine A injection, operational treatment, the best basic treatment
* Other: operational treatment, the best basic treatment
* Drug: Huperzine A injection, interventional treatment, the best basic treatment
* Other: Interventional treatment, the best basic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70; The patients were proved to be aneurysmal subarachnoid hemorrhage by imaging examination (head CT, CT angiography (CTA), whole brain angiography (DSA)); Hunt Hess was graded I-III at admission; The patients were treated with endovascular therapy or craniotomy and clipping surgery; The time from the onset of aSAH symptoms to admission ≤ 72 hours; ⑥ The subject himself or the guardian of the subject knew and voluntarily signed the informed consent form. Exclusion Criteria: Non aneurysmal subarachnoid hemorrhage; Cognitive dysfunction existed before onset; Patients with angina pectoris, bronchial asthma, mechanical intestinal obstruction, liver and kidney insufficiency, and urinary tract obstruction; Complicated with other nervous system diseases, including nervous system degenerative diseases (Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, etc.), neuromyelitis optica, epilepsy, central nervous system infection (such as AIDS, syphilis, etc.), brain traumatic dementia, etc; Psychotic patients, according to DSM-IV-TR standards, including schizophrenia or other mental diseases, bipolar disorder, major depression or delirium; Other cholinesterase inhibitor drugs are being used; ⑦ There are uncorrectable visual and auditory disorders, and neuropsychological tests and scales cannot be completed; Have unstable or serious heart, lung, liver, kidney and hematopoietic system diseases; Pregnant or lactating women and women of childbearing age without reliable contraception, and there is no evidence of negative pregnancy; ⑩ Patients who cannot be followed up as required during the study period; ⑪ Those who are allergic to the test drug; ⑫ Those who have participated in other clinical trials in recent 3 months; ⑬ Patients who are not suitable to participate in the clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The operation group-The treatment group<br>after operational treatment: ①the best basic treatment ②i.m. huperzine A injection (0.2mg), qd, 8d. | Drug: Huperzine A injection, operational treatment, the best basic treatment<br>* intramuscular<br>|
| Other: The operation group-The control group<br>after operational treatment: ①the best basic treatment | Other: operational treatment, the best basic treatment<br>* other<br>|
| Experimental: The intervention group-The treatment group<br>after interventional treatment: ①the best basic treatment ②i.m. huperzine A injection (0.2mg), qd, 8d. | Drug: Huperzine A injection, interventional treatment, the best basic treatment<br>* intramuscular<br>|
| Other: The intervention group-The control group<br>after interventional treatment: ①the best basic treatment | Other: Interventional treatment, the best basic treatment<br>* other<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini Mental Status Examination（MMSE ） | The seven items in the scale were used for scoring, and the degree of intellectual status and cognitive impairment before treatment, during follow-up and after treatment were compared within and between groups. The higher the score, the better the intellectual state of the subjects. | 90 days after discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital anxiety and depression Scale（HADS） | The anxiety and depression subscales of the Hospital Anxiety and Depression Scale were used to screen the anxiety and depression of the subjects before treatment, at the end of medication and at the visit period after discharge, and the intra group and inter group comparisons were made. The higher the score, the more serious the anxiety or depression. | Screening period (day -4 to day 0), day 8, 30 days after discharge, 90 days after discharge and 180 days after discharge | 
| The Short Form-36 Health Survey | Calculate the eight items in the scale. Before and after treatment, the scores of each items and the total score of body and psychology were compared within and between groups. | Screening period (day -4 to day 0), 30 days after discharge, 90 days after discharge and 180 days after discharge | 
| Modified Rankin Score | The functional recovery outcomes before treatment, at the end of medication and at the visit period after discharge were evaluated by using the modified Rankin scale, and compared within and between groups. The higher the score, the worse the functional recovery. | Screening period (day -4 to day 0), day 8, 30 days after discharge, 90 days after discharge and 180 days after discharge | 
| Biological sample detection | Biological samples were tested during the screening period, during the medication period, and after the medication period to obtain drug metabolomics analysis data and disease biomarker data, and intra-group and inter-group comparisons were performed. | Screening period (day -4 to day 0), day 2, day 3, day 8 | 
| Mini Mental Status Examination（MMSE ） | The seven items in the scale were used for scoring, and the degree of intellectual status and cognitive impairment before treatment, during follow-up and after treatment were compared within and between groups. The higher the score, the better the intellectual state of the subjects. | Screening period (day -4 to day 0), day2, day 3, day 8, 30 days after discharge and 180 days after discharge |