Clinical trial NCT03546309: Safety and Efficacy of RIC in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
Official title: Safety and Efficacy of Remote Ischemic Conditioning in Pediatric Moyamoya Disease Patients Treated With Revascularization Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Moyamoya Disease
Pediatric
Keywords: pediatric moyamoya disease
remote ischemic conditioning
revascularization therapy
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: The Fifth Medical Center of the Chinese People's Liberation Army (PLA) General Hospital
First posted: 2018-06-06
Enrollment: 42
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: the incidence of major neurologic complications
timeFrame: during the perioperative period
Secondary outcomes:
measure: The score of National Institute of Health stroke scale score
timeFrame: change from baseline (preoperation) at 24 hours, 48 hours, 72 hours, and at 5-7 days or if discharged earlier
measure: The score of Modified Rankin scale score
timeFrame: change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
measure: Symptomatic intracerebral hemorrhage
timeFrame: during the first 180 days after revascularization therapy
measure: Incidence of new infarct in brain
timeFrame: during 72 hours and 180 days after revascularization therapy
measure: Angiographic outcome
timeFrame: 180 days after revascularization therapy
measure: Death and adverse event
timeFrame: 180 days after revascularization therapy
measure: Infarct volume in brain
timeFrame: during 72 hours and 180 days after revascularization therapy
measure: Distal radial pulses
timeFrame: within 7 days after RIC treatment
measure: Visual inspection for local edema
timeFrame: within 7days after RIC treatment
measure: The number of patients with erythema,and/or skin lesions related to RIC
timeFrame: within 7days after RIC treatment
measure: Palpation for tenderness
timeFrame: within 7days after RIC treatment
measure: The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure
timeFrame: within 7days after RIC treatment
measure: The number of patients with any other adverse events related to RIC intervention
timeFrame: within 7days after RIC treatment
measure: The score of ABCD2
timeFrame: change from baseline (pre-RIC treatment) at 180 days after revascularization therapy
measure: The level of S-100A4
timeFrame: change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months postoperation
measure: The level of matrix metalloproteinase 9 (MMP-9)
timeFrame: change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
measure: The level of basic fibroblast growth factor
timeFrame: change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
measure: The level of platelet derived growth factor
timeFrame: change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
measure: The level of vascular endothelial growth factor
timeFrame: change from baseline (pre-RIC treatment) at 7 days after RIC treatment, 24 (-6/+12) hours, 72 ± 6 hours and 6 months post-operation
measure: the score of PSQI
timeFrame: 0-30 days
measure: the score of SNAP-IV
timeFrame: 0-30 days
measure: cerebral perfusion status
timeFrame: 0-3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Fifth Medical Center of Chinese PLA General Hospital
state: Beijing
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.