Remote Ischemic Preconditioning for Subcortical Vascular Dementia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the remote ischemic preconditioning are effective in the treatment of mild to moderate vascular dementia.

Detailed Description
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In this randomized, double-blind, placebo-controlled trial, the investigators enrolled 52 participants aged 50-80 years. The participants had a diagnosis of subcortical vascular dementia at the neurology department of Tianjin medical university general hospital. Inclusion criteria included a clinical dementia rating 1-2; a mini-mental state examination score 15-26; and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. All participants received standard medical management.Participants in the remote ischemic preconditioning group underwent 5 brief cycles consisting of bilateral upper limb ischemia followed by reperfusion. The remote ischemic precondition procedure was performed once daily over 180 consecutive days. Cognitive impairment assessment scale ( Hopkins Verbal Learning Test,HVLT;Symbol digital modalities tes,SDMT;judgement line orientation, JLO;trail making test A and B,TMT-A/B;chinese word fluency test;Activity of Daily Living Scale,ADL;Neuropsychiatric Inventory,NPI), serological inflammatory markers:hypersensitive C-reactive protein（hs-CRP）、plasma tumor necrosis factor-α(TNF-α)、interleukin-1β(IL-1β)、interleukin-6 (IL-6)、α1-antichymotrypsin),and MRI diffusion tensor imaging, DTI were compared with the untreated control group.

Official Title
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Remote Ischemic Preconditioning for Subcortical Vascular Dementia

Conditions
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Subcortical Vascular Dementia

Intervention / Treatment
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* Device: Doctormate® (200mmHg)
* Device: Doctormate® (60mmHg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of vascular dementia In three months without cerebral infarction MMSE 15 to 26 points;CDR 1-2 points;MoCA < 26 points MRI showed subcortical ischemic cerebrovascular disease. Exclusion Criteria: AD 、 FTD, DLB and other causes of dementia. Cortical/subcortical infarction Cortex watershed infarction Cerebral hemorrhage Hydrocephalus Other special causes of white matter lesions such as multiple sclerosis, sarcoidosis, radiation encephalopathy, etc. Cannot complete aphasia neuropsychological assessment. Genetic or inflammatory small vascular disease. Serious cardiovascular, lung, liver, kidney, endocrine, such as infection disease. Alcohol poisoning; Cancer Hypothyroidism Schizophrenia;Hamilton depression rating scale > 17 points. Can not complete MRI.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Doctormate® (200mmHg)<br>Patients will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) once daily for 6 months | Device: Doctormate® (200mmHg)<br>* Limb ischemia was induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®) inflating tourniquets to 200mmHg.<br>|
| Sham Comparator: Doctormate® (60mmHg)<br>Patients will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (60mmHg) once daily for 6 months | Device: Doctormate® (60mmHg)<br>* Limb ischemia was induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®) inflating tourniquets to 60mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive impairment assessment scale-HVLT | Comparing two groups of participants score changes in Short-term auditory verbal memory、learning rate and learning strategies. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-SDMT | Comparing two groups of participants score changes in-attention. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-JLO | Comparing two groups of participants score changes in spatial perception and orientation ability. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-ADL | Comparing two groups of participants score changes in daily life ability. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-TMT | Comparing two groups of participants score changes in this test.This test reflects notice, order, mental flexibility, visual search and motor function, and set transfer (set shifting), at the same time reflect the hand-eye coordination, spatial perception and pay attention to ability. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-NPI | Comparing two groups of participants score changes in mental behavior symptoms. | At the first day/sixth month after randomization | 
| Cognitive impairment assessment scale-Chinese auditory learning test | Comparing two groups of participants score changes in speech ACTS and breadth of knowledge. | At the first day/sixth month after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serological inflammatory markers-hs-CRP | Collecte venous blood from two groups of paticipants at the first day/sixth month,detect the inflammatory factors by ELISA and compare the changes between the two groups. | At the fist day/sixth month after randomization | 
| Serological inflammatory markers-TNF-a | Collecte venous blood from two groups of paticipants at the first day/sixth month,detect the inflammatory factors by ELISA and compare the changes between the two groups. | At the fist day/sixth month after randomization | 
| Serological inflammatory markers-IL - 1b | Collecte venous blood from two groups of paticipants at the first day/sixth month,detect the inflammatory factors by ELISA and compare the changes between the two groups. | At the fist day/sixth month after randomization | 
| Serological inflammatory markers-IL - 6 | Collecte venous blood from two groups of paticipants at the first day/sixth month,detect the inflammatory factors by ELISA and compare the changes between the two groups. | At the fist day/sixth month after randomization | 
| Serological inflammatory markers-ACT | Collecte venous blood from two groups of paticipants at the first day/sixth month,detect the inflammatory factors by ELISA and compare the changes between the two groups. | At the fist day/sixth month after randomization | 
| Imaging markers-DTI | To evaluate two groups of whole brain white matter (whole brain white matter, WBWM) and apparent normal white matter (normal appearing white matter, NAWM) difference of MD and FA before and after the treatment , to evaluate whether the treatment group more helpful to improve the neural axon damage. | At the fist day/sixth month after randomization | 
| Imaging markers-Routine MRI | To evaluate two sets of T2 weighted white matter lesions volume (T2 weighted lesion volume, T2WLV) before and after the treatment. | At the fist day/sixth month after randomization |