Hereditary Cerebral Small Vessel Diseases Registry-Trial Ready Cohort

NCT06512376 | Active Not Recruiting DMC

• 1 other identifier: KY-2022-074-02
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

We took hereditary cerebral small vessel disease (hCSVD) patients as our main subjects, aiming to establish a platform for a comprehensive evaluation and long-term follow-up. Deeply explore the pathophysiological mechanism of hCSVD, which may render the theoretical basis for the treatment and management of hCSVD.

Conditions

Cerebral Small Vessel Diseases; Hereditary

Keywords

hCSVD; multi-center; prospective; continuous; registry

Outcome Measures

Primary Outcomes (4)

• The epidemiological features

  Any epidemiological informations

  at baseline

• The clinical features

  Clinical symptoms and physical examination

  5 years

• The radiography features

  Neuroimaging markers collected by MRI

  at baseline

• A novel pathogenic gene for hereditary cerebrovascular disease in the Chinese population

  Genetic testing with the blood sample

  at baseline

Secondary Outcomes (2)

• Etiology and pathogenesis

  at baseline

• Long-term changes of radiography features

  5 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

hCSVD with identified gene mutations, and highly-suspected hCSVD without any identified gene mutation

You may qualify if:

• All ages, male or female
• Carriers of the pathogenic genes mutation (mutation with unknown clinical significance/ suspected pathogenic mutation/ pathogenic mutation) of hCSVD confirmed by the gene tests, including but not limited to NOTCH3, HTPA1, CTSA, GLA, TREX1, COL4A1/2, or highly-suspected hCSVD2
• CSVD related abnormalities on brain MRI, any 1 or more of:
• White matter hyperintensities, Fazekas score3 ≥1
• ≥1 newly-occurred lacunar infarcts
• ≥1 old lacunar infarcts
• ≥3 cerebral microbleeds
• Informed consent signed

You may not qualify if:

• Diagnosis of mental disorders according to DSM-V and unable to be compliant to the research
• Patients with life expectancy less than one year due to any advanced disease, e.g., malignant tumor
• Patients unable to return for follow-up visits due to some reasons

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100050, China

Location

Related Publications (15)

• Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689-701. doi: 10.1016/S1474-4422(10)70104-6.

  PMID: 20610345 RESULT

• Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496. Epub 2011 Jul 21.

  PMID: 21778438 RESULT

• Nam KW, Kwon HM, Lim JS, Han MK, Nam H, Lee YS. The presence and severity of cerebral small vessel disease increases the frequency of stroke in a cohort of patients with large artery occlusive disease. PLoS One. 2017 Oct 9;12(10):e0184944. doi: 10.1371/journal.pone.0184944. eCollection 2017.

  PMID: 28991905 RESULT

• Federico A, Di Donato I, Bianchi S, Di Palma C, Taglia I, Dotti MT. Hereditary cerebral small vessel diseases: a review. J Neurol Sci. 2012 Nov 15;322(1-2):25-30. doi: 10.1016/j.jns.2012.07.041. Epub 2012 Aug 4.

  PMID: 22868088 RESULT

• Tan R, Traylor M, Rutten-Jacobs L, Markus H. New insights into mechanisms of small vessel disease stroke from genetics. Clin Sci (Lond). 2017 Apr 1;131(7):515-531. doi: 10.1042/CS20160825.

  PMID: 28302914 RESULT

• Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke. 2010 Apr;41(4):630-4. doi: 10.1161/STROKEAHA.109.568402. Epub 2010 Feb 18.

  PMID: 20167921 RESULT

• Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004 Sep;127(Pt 9):2031-8. doi: 10.1093/brain/awh223. Epub 2004 Jun 30.

  PMID: 15229130 RESULT

• de Boer I, Pelzer N, Terwindt G. Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations. 2019 Sep 19. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK546576/

  PMID: 31536185 RESULT

• Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS. Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology. Eur J Neurol. 2020 Jun;27(6):909-927. doi: 10.1111/ene.14183. Epub 2020 Mar 20.

  PMID: 32196841 RESULT

• Peters N, Freilinger T, Opherk C, Pfefferkorn T, Dichgans M. Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL. J Neurol Sci. 2007 Sep 15;260(1-2):100-5. doi: 10.1016/j.jns.2007.04.015. Epub 2007 May 24.

  PMID: 17531269 RESULT

• Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, Lemay R, Linthorst GE, Packman S, Scott CR, Waldek S, Warnock DG, Weinreb NJ, Wilcox WR. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015 May;52(5):353-8. doi: 10.1136/jmedgenet-2014-102797. Epub 2015 Mar 20.

  PMID: 25795794 RESULT

• Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001 Jun 6;285(21):2743-9. doi: 10.1001/jama.285.21.2743.

  PMID: 11386930 RESULT

• Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.

  PMID: 27509102 RESULT

• Rutten JW, Dauwerse HG, Peters DJ, Goldfarb A, Venselaar H, Haffner C, van Ommen GJ, Aartsma-Rus AM, Lesnik Oberstein SA. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept. Brain. 2016 Apr;139(Pt 4):1123-35. doi: 10.1093/brain/aww011. Epub 2016 Feb 19.

  PMID: 26912635 RESULT

• Liu XY, Gonzalez-Toledo ME, Fagan A, Duan WM, Liu Y, Zhang S, Li B, Piao CS, Nelson L, Zhao LR. Stem cell factor and granulocyte colony-stimulating factor exhibit therapeutic effects in a mouse model of CADASIL. Neurobiol Dis. 2015 Jan;73:189-203. doi: 10.1016/j.nbd.2014.09.006. Epub 2014 Sep 22.

  PMID: 25251607 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine samples will be collected at baseline, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years to test genetic and metabolomic markers.

MeSH Terms

Conditions

Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Yilong Wang, MD+PhD

  Capital Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 22, 2024
• Study Start: July 19, 2022
• Primary Completion (Estimated): July 19, 2027
• Study Completion (Estimated): July 19, 2027
• Last Updated: July 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)