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Clinical Research

 

Brain Vascular Malformation Consortium (Brain AVM Study)

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BVMC_Logo

Clinical research aims to advance medical knowledge by studying people. The study, entitled “Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia (HHT)” is part of a major effort of the NIH to support research on rare diseases. Cure HHT has joined forces with two other rare diseases to form the Brain Vascular Malformation Consortium (BVMC). The Brain Vascular Malformation Consortium (BVMC; U54NS065705) is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). This is a five year contract award.

HOW CAN I ENROLL IN THE BVMC STUDY?

Principal Investigators
  • Michael Lawton, MD, Barrow Neurological Institute
  • Marie Faughnan, MD, MSc, University of Toronto / St. Michael's Hospital

HHT Centers of Excellence across North America, along with Cure HHT (also known as the HHT Foundation International, Inc.) are now actively recruiting HHT patients to participate in this NIH funded study. The goal of this research is to determine what genetic and clinical factors signal high risk for hemorrhage from brain AVMs. These risks have never been fully assessed for patients with HHT. Ultimately, the results will help doctors make decisions about brain AVM treatment for individual patients and will drive further research in brain AVM therapies.

Official BVMC website

Additional enrollment information

HHT patients with a Brain AVM, whether or not its been treated, should contact Leslie Perry, Research Coordinator by email or 410-357-9932 to determine eligibility. NO TRAVEL required, information gathering only, one hour of your time - this is all that is needed to impact this critical area of study!

Eligibility

  • Definite Clinical or Genetic Diagnosis of HHT
  • Brain AVM diagnosis whether treated or untreated
  • Live in the United States, Canada, or Europe (Cure HHT can recruit patients worldwide)
  • Be at least 3 years of age

BVMC Study Aims

  1. Correlate brain AVM and brain AVM phenotypes (lesion number, lesion type, initial presentation, etc.) with mRS change (primary outcome) and with intracranial hemorrhage (ICH)
  2. Extend our measurement of AVM bleeding risk in HHT to include the much more common bleeding phenotype in HHT, chronic nasal bleeding, as we hypothesize that there are shared predictors of bleeding across affected organs in HHT.
  3. Identify genetic predictors and circulating biomarkers of severe bleeding (PRO-CB) and brain outcomes in HHT.

HHT-Related Publications as a direct result of the Brain AVM Study

  1. Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schrum SD, James M, Quinnine N, Bharatha A, terBrugge KG, White RI Jr. Brain Arteriovenous Malformations associated with Hereditary Hemorrhagic Telangiectasia: Genotype-Phenotype Correlations.  Am J Med Genet A 2012 Nov;158A(11):2829-34 Epub 2012 Sep 18. PMID: 22991266 PMCID: PMC3610331  https://pubmed.ncbi.nlm.nih.gov/22991266/
  2. Bharatha A, Faughnan ME, Kim H, Pourmohamad T, Krings T, Bayrak-Toydemir P, Pawlikowska L, McCulloch CE, Lawton MT, Dowd CF, Young WL, terBrugge KG. Brain Arteriovenous Malformation Multiplicity Predicts the Diagnosis of Hereditary Hemorrhagic Telangiectasia: Quantitative Assessment. Stroke 2012 Jan;43(1):72-8. Epub 2011 Oct 27. PMID: 22034007 PMCID: PMC3727386 https://pubmed.ncbi.nlm.nih.gov/22034007/
  3. Akers A, Ball KL, Clancy M, Comi A, Faughnan ME, Gopal-Srivastava R, Jacobs TP, Kim H, Krischer J, Marchuk DA, McCulloch CE, Morrison L, Moses M, Moy CS, Pawlikowska L, Young WL; on behalf of the BVMC. Brain Vascular Malformation Consortium: Overview, Progress and Future Directions. J Rare Disorders 2013;1(1):1-15. PMID: 25221778 PMCID: PMC4160161  https://pubmed.ncbi.nlm.nih.gov/25221778/
  4. Cheng KH, Mariampillai A, Lee K, Vuong B, Luk TW, Ramjist J, Curtis A, Jakubovic H, Kertes P, Letarte M, Faughnan ME, Yang VX. Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. J Biomed Opt. 2014 Aug; 19(8):086015.   PMCID: PMC4407667  https://pubmed.ncbi.nlm.nih.gov/25140883/
  5. Latino GA, Kim H, Nelson J, Pawlikowska L, Young W, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. Severity score for hereditary hemorrhagic telangiectasia.  Orphanet J Rare Dis. 2014 Dec 29;9:188.   PMCID: PMC4302697  https://pubmed.ncbi.nlm.nih.gov/25928712/
  6. Kim H, Nelson J, Krings T, terBrugge KG, McCulloch CE, Lawton MT, Young WL, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. Hemorrhage rates from brain arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia.  2015 May;46(5):1362-1364.   PMCID: PMC4415515  https://pubmed.ncbi.nlm.nih.gov/25858236/
  7. Krings T, Kim H, Power S, Nelson J, Faughnan ME, Young WL, terBrugge KG, Brain Vascular Malformation Consortium HHT Investigator Group. Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging features and genotype-phenotype correlations.  AJNR Am J Neuroradiol. 2015 May;36(5):863-870.   PMCID: PMC4433843  https://pubmed.ncbi.nlm.nih.gov/25572952/
  8. Pawlikowska L, Nelson J, Guo DE, McCulloch CE, Lawton MT, Young WL, Kim H, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with ENG mutations, but not in patients with ACVRL1 mutations.  Am J Med Genet A. 2015 Jun;167(6):1262-1267.   PMCID: PMC4449292  https://pubmed.ncbi.nlm.nih.gov/25847705/
  9. Kasthuri RS, Montifar M, Nelson J, Kim H, Lawton MT, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia.  Am J Hematol. 2017 Jun 22.  (Epub ahead of print).    PMCID: PMC5997494  https://pubmed.ncbi.nlm.nih.gov/28639385/
  10. Meybodi AT, Kim H, Nelson J, Hetts SW, Krings T, terBrugge KG, Faughnan ME, Lawton MT, Brain Vascular Malformation Consortium HHT Investigator Group. Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study.  2018 Jan 1;82(1):35-47.   PMCID: PMC5732039  https://pubmed.ncbi.nlm.nih.gov/28973426/
  11. Pawlikowska L, Nelson J, Guo D, McCulloch C, Lawton M, Kim H, Faughnan ME, Brain Vascular Malformation Consortium HHT Investigator Group. Association of Common Candidate Variants with Vascular Malformations and Intracranial Hemorrhage in Hereditary Hemorrhagic Telangiectasia.  Mol Genet Genomic Med. 2018 May;6(3):350-356.   PMCID: PMC6014448  https://pubmed.ncbi.nlm.nih.gov/29932521/
  12. Klostranec JM, Chen L, Mathur S, McDonald J, Faughnan ME, Ratjen F, Krings T. A theory for polymicrogyria and brain arteriovenous malformations in HHT. 2019 Jan 1;92(1):34-42. PMID: 30584075 PMCID: PMC6336165  https://pubmed.ncbi.nlm.nih.gov/30584075/
  13. Cannavicci A, Zhang Q, Dai SC, Faughnan ME, Kutryk MJB. Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia 1.  Can J Physiol Pharmacol. 2019 Jun;97(6):562-569. doi: 10.1139/cjpp-2018-0508. Epub 2018 Dec 4. PMID: 30512964  PMCID: PMC6886744  https://pubmed.ncbi.nlm.nih.gov/30512964/
  14. Thompson, K., Nelson J, Kim H, Pawlikowska L, Marchuk DA, Lawton MT, Faughnan ME and the Brain Vascular Malformation Consortium HHT Investigator Group. Predictors of Mortality in Hereditary Hemorrhagic Telangiectasia. Orphanet J Rare Dis. 2021 Jan 6;16(1):12. PMID: 33407668 PMCID: PMC7789194  https://pubmed.ncbi.nlm.nih.gov/33407668/
  15. Kilian A, Latino GA, White AJ, Clark D, Chakinala MM, Ratjen F, McDonald J, Whitehead K, Gossage JR, Lin D, Henderson K, Pollak J, McWilliams JP, Kim H, Lawton MT,Faughnan ME; the Brain Vascular Malformation Consortium HHT Investigator Group. Genoptype-Phenotype Correlations in Children with HHT. J Clin Med. 2020 Aug 22;9(9):2714. doi: 10.3390/jcm9092714.  PMID: 32842615 PMCID: PMC7565052  https://pubmed.ncbi.nlm.nih.gov/32842615/
  16. Zhang Q, Wang C, Cannavicci A, Faughnan ME, Kutryk MJ. Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells. Transl Res. 2021 Apr 22:S1931-5244(21)00087-6. doi: 10.1016/j.trsl.2021.04.005. Online ahead of print. PMID: 33894400
  17. Cardinell JL, Ramjist JM, Chen C, Shi W, Nguyen NQ, Yeretsian T, Choi M, Chen D, Clark DS, Curtis A, Faughnan ME, Yang VXD and Brain Vascular Malformation Consortium HHT Investigator Group. Quantification metrics for telangiectasia using optical coherence tomography. Sci Rep. 2022 Feb 2;12(1):1805. doi: 10.1038/s41598-022-05272-1. PMID: 35110554 PMCID:PMC8810896
  18. Thompson KP, Nelson J, Kim H, Weinsheimer SM, Marchuk DA, Lawton MT, Krings T, Faughan ME and Brain Vascular Malformation Consortium HHT Investigator Group. Utility of Modified Rankin Scale for Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia. Orphanet J Rare Dis. 2021: Sep 19;16(1):390. doi: 10.1186/s13023-021-02012-y.  PMID: 34538258 PMCID: PMC8451134
  19. Wetzel-Strong S, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA.  Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.  PMID: 34479577 PMCID: PMC8414780
  20. Keränen S, Suutarinen S, Laakkkonen J, Guo D, Pawlikowska L, Jahromi BR, Rauramaa T, Yla-Herttula S, Marchuk DA, Krings T, Koivisto T, Lawton MT, Radovanovic I, Kim H, Faughnan ME, Frosen J. Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in brain AVMs vessels and associates with inflammation. Acta Neurochir (Wein). 2021 Sep;163(9):2503-2514. doi: 10.1007/s00701-021-04895-z. Epub 2021 Jun 29. PMID: 34185176 PMCID: PMC8357659
  21. Cannavicci A, Zhang Q, Faughnan ME, Kutryk MJB. MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways. Genes 2022, 13, 665. https://doi.org/10.3390/genes13040665

In-press Publications:

  1. Ananiadis T, Faughnan ME, Clark D, Prabhudesai P, Kim H, Lawton MT, Vozoris NT; Brain Vascular Malformation Consortium HHT Investigator Group. Neurovascular complications and pulmonary arteriovenous malformation feeding artery size. Annals of the American Thoracic Society. 2022. In press.

Submitted Publications:

HHT BVMC Papers in progress:

  1. Determinants of Anemia in Hereditary Hemorrhagic Telangiectasia Patient. Scott G, Stein G, Sykes J, Clark D,Vozoris N, Kasthuri R, Faughnan ME and Brain Vascular Malformation Consortium HHT Investigator Group.
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