血行再建療法を受けた小児モヤモヤ病患者におけるRICの安全性と有効性 (RIC-PMD)
血行再建療法を受けた小児モヤモヤ病患者における遠隔虚血性コンディショニングの安全性と有効性
Revascularization surgery has been the standard treatment to prevent ischemic stroke in pediatric Moyamoya disease (MMD) patients with ischemic symptoms. However, perioperative complications, such as hyperperfusion syndrome, new infarct on imaging, or ischemic stroke, are inevitable. Remote ischemic conditioning (RIC) is a noninvasive and easy-to-use neuroprotective strategy, and it has potential effects on preventing hyperperfusion syndrome and ischemic infarction.
調査の概要
詳細な説明
This study will provide insights into the preliminary proof of principle, safety, and efficacy of RIC in pediatric MMD patients undergoing revascularization surgery therapy, and this data will provide parameters for future larger scale clinical trials if efficacious.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Xunming Ji, MD PhD
- 電話番号：+8613911077166
- メール：807595234@qq.com;
研究連絡先のバックアップ
- 名前：Sijie Li, MD
- 電話番号：+8613581610258
- メール：phoenix0537@sina.com
研究場所
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Beijing Municipality
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Beijing、Beijing Municipality、中国
- 募集
- The Fifth Medical Center of Chinese PLA General Hospital
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コンタクト：
- xunming Ji
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Age: ≥0 and ≤18
- All of the patients underwent digital subtraction angiography and met the current diagnostic criteria recommended by the Research Committee on MMD (Spontaneous Occlusion of the Circle of Willis) of the Ministry of Health and Welfare of Japan in 2012
- Suzuki stages concentrated in Stage III and IV
- Presentation with ischemic symptoms, such as transient ischemic attack (TIA), headache, seizure, hemorrhagic stroke, and ischemic stroke confirmed by MRI
- Informed consent obtained from patient or acceptable patient's surrogate
Exclusion Criteria:
- Severe hepatic or renal dysfunction
- Severe hemostatic disorder or severe coagulation dysfunction
- Patients with unilateral MMD or the presence of secondary moyamoya phenomenon caused by autoimmune disease, Down syndrome, neurofibromatosis, leptospiral infection, or previous skull-base radiation therapy
- Any of the following cardiac disease - rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with participation
- Serious, advanced, or terminal illnesses with anticipated life expectancy of less than one year
- Patient participating in a study involving other drug or device trial study
- Patients with existing neurological or psychiatric disease that would confound the neurological or functional evaluations
- Unlikely to be available for follow-up for 3 months
- Contraindication for RIC - severe soft-tissue injury, fracture, or peripheral vascular disease in the upper limbs.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：RIC group
Patients allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 50 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs.They will also accept medication treatment by professional neurologists. |
Patients allocated to the RIC group will undergo RIC procedure during which bilateral arm cuffs are inflated to a pressure of 50 mmHg over systolic blood pressure for five cycles of 5 min followed by 5 min of relaxation of the cuffs. |
|
他の：Medication group
Patients allocated to the medication group will accept medication treatment by professional neurologists. |
Patients allocated to Medication group will accept medication treatment by professional neurologists |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
the incidence of major neurologic complications
時間枠：during the perioperative period
|
Including transient ischemic attack, cerebral infarction, intracranial hemorrhage, and seizures. |
during the perioperative period
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The score of National Institute of Health stroke scale score
時間枠：change from baseline (preoperation) at 24 hours, 48 hours, 72 hours, and at 5-7 days or if discharged earlier
|
National Institute of Health Stroke Scale (NIHSS) is considered as a standardized assessment of neurological functions in the acute phase of stroke, and it is generally used to quantify patient's neurological impairments on 15 items in 11 fields of different neurological status.The score of the scale ranges from 0 to 42.And higher score indicates worse neurological function. |
change from baseline (preoperation) at 24 hours, 48 hours, 72 hours, and at 5-7 days or if discharged earlier
|
|
The score of Modified Rankin scale score
時間枠：change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
|
The Modified Rankin Scale Score (mRS) is the most comprehensive and most widely used primary outcome measurement to assess the neurological functional disability in contemporary acute stroke trials. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranges from 0 (no symptom) to 5 (severe disability) and 6 (death). We will use mRS to evaluate the degree of disability or dependence during daily activities. The mRS will be assessed by certified study investigator, who is blinded to the treatment assignment, at 90 days postoperation. The distribution of mRS will be compared between groups |
change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
|
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Symptomatic intracerebral hemorrhage
時間枠：during the first 180 days after revascularization therapy
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Symptomatic intracranial hemorrhage, including any subarachnoid hemorrhage associated with clinical symptoms and symptomatic intracerebral hemorrhage. Head computed tomography or magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment. |
during the first 180 days after revascularization therapy
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Incidence of new infarct in brain
時間枠：during 72 hours and 180 days after revascularization therapy
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Head MRI is a precise method which is commonly used to evaluate weather there's new infarct in brain. |
during 72 hours and 180 days after revascularization therapy
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Angiographic outcome
時間枠：180 days after revascularization therapy
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Angiographic outcome will be assessed following Matsushima's criteria (proportion of the middle cerebral artery territory with revascularization from collaterals from the external carotid artery through the burr holes): Grade A: >2/3; Grade B: between 1/3 and 2/3; Grade C: <1/3. |
180 days after revascularization therapy
|
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Death and adverse event
時間枠：180 days after revascularization therapy
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All causes of death will be included to compute mortality at 180 days postoperation, and mortality will be compared between groups. Any adverse event will be reported and its relationship with the RIC intervention will be evaluated. |
180 days after revascularization therapy
|
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Infarct volume in brain
時間枠：during 72 hours and 180 days after revascularization therapy
|
Head MRI is a precise method which is commonly used to evaluate infarct size. |
during 72 hours and 180 days after revascularization therapy
|
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Distal radial pulses
時間枠：within 7 days after RIC treatment
|
professional doctors will check the distal radial pulses |
within 7 days after RIC treatment
|
|
Visual inspection for local edema
時間枠：within 7days after RIC treatment
|
Professional oculists will check the fundus oculi to evaluate whether there is local edema. |
within 7days after RIC treatment
|
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The number of patients with erythema,and/or skin lesions related to RIC
時間枠：within 7days after RIC treatment
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Professional doctors will check it and the investigator will record the number. |
within 7days after RIC treatment
|
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Palpation for tenderness
時間枠：within 7days after RIC treatment
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Professional doctors will check it. |
within 7days after RIC treatment
|
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The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure
時間枠：within 7days after RIC treatment
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The investigator will record the number. |
within 7days after RIC treatment
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The number of patients with any other adverse events related to RIC intervention
時間枠：within 7days after RIC treatment
|
The investigator will record the number. |
within 7days after RIC treatment
|
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The score of ABCD2
時間枠：change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
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We use this scale to evaluate the patients' risk of stroke who with TIA .The score of the scale ranges from 0 to 7, and the higher score indicates higher risk of stroke in the patients who with TIA.The scale will be assessed by qualified investigator who are blinded to the treatment assignment |
change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
|
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The level of S-100A4
時間枠：change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months postoperation
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Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation |
change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months postoperation
|
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The level of matrix metalloproteinase 9 (MMP-9)
時間枠：change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation |
change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
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The level of basic fibroblast growth factor
時間枠：change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation |
change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
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The level of platelet derived growth factor
時間枠：change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation |
change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
|
The level of vascular endothelial growth factor
時間枠：change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation |
change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
|
|
the score of PSQI
時間枠：0-30 days
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The Pittsburgh Sleep Quality Index (PSQI) is a standardized questionnaire used to assess sleep quality and disturbances over a one-month time interval. |
0-30 days
|
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the score of SNAP-IV
時間枠：0-30 days
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SNAP-IV (Swanson, Nolan, and Pelham Teacher and Parent Rating Scale) is a widely used assessment tool designed to evaluate behavioral and emotional problems in children and adolescents. |
0-30 days
|
|
cerebral perfusion status
時間枠：0-3 months
|
cerebral perfusion status in the operation side at 3 months posttreatment as assessed by magnetic resonance perfusion |
0-3 months
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- Kuriyama S, Kusaka Y, Fujimura M, Wakai K, Tamakoshi A, Hashimoto S, Tsuji I, Inaba Y, Yoshimoto T. Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey. Stroke. 2008 Jan;39(1):42-7. doi: 10.1161/STROKEAHA.107.490714. Epub 2007 Nov 29.
- Kim SK, Seol HJ, Cho BK, Hwang YS, Lee DS, Wang KC. Moyamoya disease among young patients: its aggressive clinical course and the role of active surgical treatment. Neurosurgery. 2004 Apr;54(4):840-4; discussion 844-6. doi: 10.1227/01.neu.0000114140.41509.14.
- Kim JE, Oh CW, Kwon OK, Park SQ, Kim SE, Kim YK. Transient hyperperfusion after superficial temporal artery/middle cerebral artery bypass surgery as a possible cause of postoperative transient neurological deterioration. Cerebrovasc Dis. 2008;25(6):580-6. doi: 10.1159/000132205. Epub 2008 May 16.
- Fujimura M, Shimizu H, Inoue T, Mugikura S, Saito A, Tominaga T. Significance of focal cerebral hyperperfusion as a cause of transient neurologic deterioration after extracranial-intracranial bypass for moyamoya disease: comparative study with non-moyamoya patients using N-isopropyl-p-[(123)I]iodoamphetamine single-photon emission computed tomography. Neurosurgery. 2011 Apr;68(4):957-64; discussion 964-5. doi: 10.1227/NEU.0b013e318208f1da.
- Funaki T, Takahashi JC, Takagi Y, Kikuchi T, Yoshida K, Mitsuhara T, Kataoka H, Okada T, Fushimi Y, Miyamoto S. Unstable moyamoya disease: clinical features and impact on perioperative ischemic complications. J Neurosurg. 2015 Feb;122(2):400-7. doi: 10.3171/2014.10.JNS14231. Epub 2014 Nov 28.
- Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F, Wu W, Shi J, Duan Y, Zhang R, Zhang J, Sun Y, Zhang H, Ling F, Wang Y, Feng W, Ding Y, Ovbiagele B, Ji X. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation. 2017 Apr 4;135(14):1325-1335. doi: 10.1161/CIRCULATIONAHA.116.024807. Epub 2017 Feb 7.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
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最終確認日
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