- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03509701
Reversible Cerebral Vasoconstriction Syndrome and Varicella Zoster Virus (RCVS&VZV)
Association Between Reversible Cerebral Vasoconstriction Syndrome and Herpes Zoster Infection
Study Overview
Status
Intervention / Treatment
Detailed Description
In the previous pilot study, reactivation of VZV was confirmed in 63.6% of the patients as having RCVS by cell mediated immune response (CMI) test and 18.2% by Saliva PCR. None of patients who were simply stressed showed reactivation of VZV. Considering about 20% had false negative results in angiographic findings of RCVS, we set the effect size as 0.63 in group of subjects and 0.12 in group of controls. Using alpha values of 0.05 and beta values of 0.2, we calculated the target number of the study. If the ratio of cases to controls is 1:2, 9 case-patients and 18 control-patients were needed and if the ratio is 1:3, 8 case-patients and 24 control-patients were needed. We expect to enroll 10 case-patients and 20 to 30 control-patients within two years, considering the drop rate of 10~20%.
Baseline clinical information regarding age, sex, smoking history and medical comorbidities including hypertension (treated, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg at discharge), diabetes (treated, fasting blood glucose ≥126 mg/d), hyperlipidemia (treated, total cholesterol level ≥200 mg/dl or low-density lipoprotein level ≥140 mg/dl) and coronary artery disease will be collected on admission. Laboratory tests, including complete blood count, blood chemistry, c-reactive protein and erythrocyte sediment rate wil be performed. Images of brain MRI, MR angiography, CT angiography or digital substraction angiography will be gathered if present.
Tests for VZV specific antibody responses and T-cell mediated immune response will be performed by VZV specific ELISA and IFN-γ ELISPOT, respectively. Result for T cell responses will be shown as spot number per 10^6 PBMCs. On the day of blood sample collection, plasma will be isolated and freezed (-80℃). Peripheral mononuclear cells will be separated from the remaining blood samples and keep freezed (-190℃). Melt the frozen peripheral mononuclear cells and inoculate them on a plate (T-Track human IFN-γ, Lophius) with anti-human IFN-γ antibody and inoculate VZV lysate (Microbix) 50 ug/mL on them. After incubating 24 hours, the staining will be performed and the spot will be read in a automated ELISPOT reader (ELR07 reader system, Autoimmune Diagnostika GmbH).
For statistical analysis, patients with thunderclap headache will divided into two groups according to the presence of RCVS. Among them, the rate of infection with varicella zoster virus will be compared and analyzed. Fisher's exact test, Mann-Whitney test, Pearson correlation will be performed. Also, logistic regression analysis will be used, and covariates will be adjusted if needed. Sensitivity and specificity of tests for reactivation of VZV and RCVS will be analyzed too.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Sung-Han Kim, MD.PhD
- Phone Number: 82-2-3010-3305
- Email: kimsunghanmd@hotmail.com
Study Contact Backup
- Name: Hyuk Sung Kwon, MD
- Phone Number: 82-31-560-2078
- Email: kwonhs@hanyang.ac.kr
Study Locations
-
-
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Seoul, Korea, Republic of, 138-736
- Recruiting
- Asan Medical Center, University of Ulsan College of Medicine
-
Contact:
- Sung-Han Kim, M.D.
- Phone Number: 3305 +82-2-3010-3114
- Email: shkimmd@amc.seoul.kr
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Contact:
- Yeon-Joo Lee
- Phone Number: 5224 +82-2-3010-3114
- Email: yeonjoo@amc.seoul.kr
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Principal Investigator:
- Sung-Han Kim, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients with thunderclap headache and suspicious of intracranial vascular lesion by computed tomographic angiography (CTA) or magnetic resonance angiography (MRA).
Exclusion Criteria:
- Patients with life threatening medical condition
- Pregnant or scheduled for pregnancy
- Unwilling or unable to give informed consent
- Patients who confirmed vasculitis
- Patients with genetic disease for vascular disorder
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Subject (RCVS)
Patients who meet the definition of RCVS.
(1) acute and severe headache with or without focal deficits or seizures, (2) uniphasic course without new symptoms more than 1 month after clinical onset, (3) segmental vasoconstriction of cerebral arteries shown by computed tomography angiography (CTA), magnetic resonance angiography (MRA) or transfemoral cerebral angiography (TFCA),(4) normal or near normal cerebrospinal fluid analysis and (5) complete or substantial normalisation of arteries shown by follow-up angiography within 12 weeks.
|
Check VZV-specific antibody response, VZV specific T-cell mediated immune response by IFN-γ ELISPOT assay from blood, and real-time PCR results from saliva
Other Names:
|
Control
Patients with thunderclap headache and intracranial stenosis, but not diagnosed as RCVS.
|
Check VZV-specific antibody response, VZV specific T-cell mediated immune response by IFN-γ ELISPOT assay from blood, and real-time PCR results from saliva
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infection or reactivation of varicella zoster virus (VZV)
Time Frame: At the time of enrolled.
|
Compare prevalence of infection or reactivation of VZV in case-patients and control-patients.
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At the time of enrolled.
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Miller TR, Shivashankar R, Mossa-Basha M, Gandhi D. Reversible Cerebral Vasoconstriction Syndrome, Part 1: Epidemiology, Pathogenesis, and Clinical Course. AJNR Am J Neuroradiol. 2015 Aug;36(8):1392-9. doi: 10.3174/ajnr.A4214. Epub 2015 Jan 15.
- Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, Calabrese LH. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol. 2011 Aug;68(8):1005-12. doi: 10.1001/archneurol.2011.68. Epub 2011 Apr 11.
- Katz BS, Fugate JE, Ameriso SF, Pujol-Lereis VA, Mandrekar J, Flemming KD, Kallmes DF, Rabinstein AA. Clinical worsening in reversible cerebral vasoconstriction syndrome. JAMA Neurol. 2014 Jan;71(1):68-73. doi: 10.1001/jamaneurol.2013.4639.
- Cuvinciuc V, Viguier A, Calviere L, Raposo N, Larrue V, Cognard C, Bonneville F. Isolated acute nontraumatic cortical subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2010 Sep;31(8):1355-62. doi: 10.3174/ajnr.A1986. Epub 2010 Jan 21.
- Kwon SU, Yun SC, Kim MC, Kim BJ, Lee SH, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Risk of stroke and transient ischaemic attack after herpes zoster. Clin Microbiol Infect. 2016 Jun;22(6):542-8. doi: 10.1016/j.cmi.2016.03.003. Epub 2016 Mar 16.
- Kim MC, Yun SC, Lee HB, Lee PH, Lee SW, Choi SH, Kim YS, Woo JH, Kim SH, Kwon SU. Herpes Zoster Increases the Risk of Stroke and Myocardial Infarction. J Am Coll Cardiol. 2017 Jul 11;70(2):295-296. doi: 10.1016/j.jacc.2017.05.015. No abstract available.
- Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol. 2006 Nov-Dec;27(10):2179-90.
- Park SY, Kim JY, Kim JA, Kwon JS, Kim SM, Jeon NY, Kim MC, Chong YP, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Diagnostic Usefulness of Varicella-Zoster Virus Real-Time Polymerase Chain Reaction Analysis of DNA in Saliva and Plasma Specimens From Patients With Herpes Zoster. J Infect Dis. 2017 Dec 27;217(1):51-57. doi: 10.1093/infdis/jix508.
- Yancy H, Lee-Iannotti JK, Schwedt TJ, Dodick DW. Reversible cerebral vasoconstriction syndrome. Headache. 2013 Mar;53(3):570-6. doi: 10.1111/head.12040.
- Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol. 2012 Oct;11(10):906-17. doi: 10.1016/S1474-4422(12)70135-7.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018-0385
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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