<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03838237</url>
  </required_header>
  <id_info>
    <org_study_id>148/int/2017</org_study_id>
    <nct_id>NCT03838237</nct_id>
  </id_info>
  <brief_title>Effect of Migalastat on Cardiac Involvement in Fabry Disease</brief_title>
  <acronym>MAIORA</acronym>
  <official_title>Effect of Migalastat on Cardiac Involvement in Fabry Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale San Donato</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amicus Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute of Biomedicine and Molecular Immunology - CNR</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ospedale San Donato</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Anderson-Fabry Disease (AFD) is one of the rare lysosomal storage disorders for which a cause&#xD;
      - specific therapy is available. Recently, a new specific drug has been marketed, namely&#xD;
      Migalastat, a small-molecule pharmacological chaperone. The effect of Migalastat on cardiac&#xD;
      involvement has been assessed so far by 2D echocardiography, demonstrating a significant&#xD;
      reduction in left ventricular (LV) mass after 18 months of therapy. Calculation of LV mass by&#xD;
      2D echocardiography is limited by geometrical assumptions and quality of echocardiographic&#xD;
      window, with a strong impact on accuracy. Cardiac Magnetic Resonance (CMR) overcomes these&#xD;
      limitations, thus representing the gold standard technique for ventricular mass, volumes and&#xD;
      function estimation. Moreover, CMR offers the unique possibility to perform a non-invasive&#xD;
      tissue characterization, including the detection of both myocardial fibrosis by Late&#xD;
      Gadolinium Enhancement and sphingolipid storage by T1 mapping. Beyond an accurate&#xD;
      morphological description and a detailed tissue characterization, a complete cardiological&#xD;
      assessment should also integrate functional data and bio-humoral profile.&#xD;
&#xD;
      This study is designed to provide a comprehensive evaluation of the therapeutic effect of&#xD;
      Migalastat (123 mg every other day) on cardiac involvement after 18 months of therapy,&#xD;
      integrating a morphological, functional and bio-humoral assessment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anderson-Fabry disease is a rare X-linked lysosomal disorder, mainly affecting&#xD;
      cardiovascular, renal and nervous systems. Cardiac injury is the leading cause of death in&#xD;
      these patients. Heart involvement is characterized by left ventricular hypertrophy (LVH),&#xD;
      myocardial scarring and/or inflammation, Bradyarrhythmias or tachyarrhythmias, heart failure&#xD;
      and represents the main cause of death in these patients. Since 2001, specific therapies&#xD;
      (enzyme replacement therapy (ERT) first and pharmacological chaperone migalastat more&#xD;
      recently) are available to treat these patients.&#xD;
&#xD;
      Migalastat is a small-molecule pharmacological chaperone stabilizing speciﬁc mutant forms of&#xD;
      the enzyme (α-Gal ) and promoting its catabolic function. These mutant forms of α-Gal are&#xD;
      deﬁned as amenable to Migalastat. In patients with amenable mutations, orally administered&#xD;
      Migalastat is a potential alternative treatment to intravenous ERT. Because of its chemical&#xD;
      nature (small molecule) and route of administration (orally), Migalastat would avoid&#xD;
      ERT-associated immunogenicity and infusion-associated reactions. Additionally, the higher&#xD;
      volume of distribution of migalastat relative to ERT suggests enhanced penetration of organs&#xD;
      and tissues. Theoretically, the chaperoning of α-Gal by Migalastat to lysosomes may better&#xD;
      mimic natural enzyme trafficking and result in more constant α-Gal activity than biweekly ERT&#xD;
      infusions.&#xD;
&#xD;
      Two main clinical studies have been published so far about safety and efficacy of Migalastat&#xD;
      in AFD, demonstrating good safety, tolerability and comparable efficacy to ERT. These studies&#xD;
      reported a significant decrease in LV mass index assessed by 2D echocardiography (-6,6 g/m2&#xD;
      in 33 patients after 18 months of therapy), mostly in patients with overt cardiac involvement&#xD;
      and greater than the changes observed with ERT (-2 g/m2 in 16 patients after 18 months of&#xD;
      therapy).&#xD;
&#xD;
      Calculation of LV mass by 2D echocardiography is based on the &quot;Devereux formula&quot;, assuming&#xD;
      that the LV is a prolate ellipsoid with a 2:1 long/short axis ratio and symmetric&#xD;
      distribution of hypertrophy. This is not always the case in AFD Cardiomyopathy, showing a&#xD;
      wide variety of hypertrophy patterns. Moreover, since linear measurements of LV wall&#xD;
      thickness and diameters are cubed in this formula, even small measurement errors in&#xD;
      dimensions or thickness have a strong impact on accuracy.&#xD;
&#xD;
      Cardiac magnetic resonance (CMR) represents the gold standard technique for ventricular mass,&#xD;
      volumes and function estimation because of the possibility to directly measure these&#xD;
      parameters without geometrical assumption. Therefore, CMR has an excellent inter-study&#xD;
      reproducibility both in normal and in pathologic hearts, overcoming 2D echocardiography.&#xD;
      Beyond its high reproducibility in LV mass measurement, CMR offers the unique possibility of&#xD;
      non-invasive tissue characterization. This concept includes both detection and quantification&#xD;
      of myocardial fibrosis by Late Gadolinium Enhancement images and application of new&#xD;
      techniques, namely T1 mapping, detecting myocardial sphingolipid storage even before LVH&#xD;
      occurs. Also, CMR allows a detailed characterization of myocardial deformation by feature&#xD;
      tracking. Feature tracking CMR (FT-CMR) approximately applies the same principles of speckle&#xD;
      tracking echocardiography (even though with differences methods of image acquisition and&#xD;
      reconstruction) in order to measure global and segmental myocardial deformation. The strength&#xD;
      of FT-CMR consists of its relatively unrestricted access to large fields of view, its high&#xD;
      spatial resolution and its relatively high signal to noise and contrast to noise ratios.&#xD;
&#xD;
      MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the&#xD;
      post-transcriptional level. MiRNAs have emerged as key regulators of several physiological&#xD;
      and pathophysiological processes. Besides their intracellular function, recent studies&#xD;
      demonstrated that miRNAs can be exported or released by cells and circulate in blood in a&#xD;
      remarkably stable form. The discovery of circulating miRNAs opens the possibilities to use&#xD;
      circulating miRNA patterns as biomarkers for several pathologies also for cardiovascular&#xD;
      diseases. In a recent study, a common microRNA signature in AFD patients regardless of gender&#xD;
      and age has been identified.15 miRNAs differentially expressed between 10 AFD subjects and 10&#xD;
      normal controls (NC) have been found. The levels of these 15 miRNAs in plasma sample of 10&#xD;
      subjects with LVH and no mutation in the Galactosidase Alpha (GLA) gene have also been&#xD;
      studied. Among these 15 miRNAs, 3 discriminated AFD patients from subjects with LVH. In&#xD;
      particular, 2 microRNAs (mir-199a-5p and mir126a-3p) were up-regulated and 1 miRNA&#xD;
      (mir-423-5p) was down-expressed in AFD patients. Interestingly, in a recent study increased&#xD;
      plasmatic levels of miR-126 and miR-199a were significantly associated with a lower major&#xD;
      adverse Cardiovascular (CV) event rate in patients with coronary artery disease. Instead,&#xD;
      elevated plasmatic levels of mir-423-5p is strongly related to the clinical diagnosis of&#xD;
      Heart Failure. Several evidences indicate that the aberrantly expressed plasmatic miRNAs in&#xD;
      AFD are linked to microvascular or macrovascular damage involved in the typical AFD&#xD;
      vasculopathy and could be attractive as diagnostic markers as well as for the monitoring of&#xD;
      the pharmacological treatment.&#xD;
&#xD;
      Integration of all these aspects allows a complete morpho-functional evaluation of cardiac&#xD;
      involvement in AFD and a detailed monitoring of the effects of specific drugs.&#xD;
&#xD;
      This study is designed to provide a comprehensive evaluation of the therapeutic effect of&#xD;
      Migalastat on cardiac involvement, integrating a morphological, functional and bio-humoral&#xD;
      assessment of heart involvement. 15 patients with amenable mutation, clinical indication to&#xD;
      Migalastat and signs of early or overt cardiac involvement with will undergo a complete&#xD;
      cardiological evaluation before and 18 months after therapy with Migalastat. The&#xD;
      cardiological assessment will include ECG, 2D echocardiography, CMR, cardio-pulmonary test,&#xD;
      dosage of peripheral biomarkers (TnT High Sensitive; NT-proBNP, mir-199a-5p and mir126a-3p,&#xD;
      mir-423-5p).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">January 22, 2021</completion_date>
  <primary_completion_date type="Actual">January 22, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Delta left ventricular mass</measure>
    <time_frame>18 months</time_frame>
    <description>Changes in left ventricular mass measured by cardiac magnetic resonance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Delta native myocardial T1 values</measure>
    <time_frame>18 months</time_frame>
    <description>Changes in native myocardial T1 values measured by cardiac magnetic resonance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delta left ventricular global longitudinal strain</measure>
    <time_frame>18 months</time_frame>
    <description>Changes in left ventricular global longitudinal strain measured by cardiac magnetic resonance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delta 3 plasmatic microRNAs levels</measure>
    <time_frame>18 months</time_frame>
    <description>Changes in mir-199a-5p, mir126a-3p, mir-423-5p levels measured by Real-Time quantitative Polymerase Cycle Reaction (RT-qPCR)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">18</enrollment>
  <condition>Fabry Disease</condition>
  <condition>Heart Diseases</condition>
  <arm_group>
    <arm_group_label>Fabry Disease patients</arm_group_label>
    <description>Patients with genetic diagnosis of Fabry Disease, clinical indication to Migalastat and signs of cardiac involvement (early or advanced) will undergo cardiological evaluation before and 18 months after therapy with Migalastat (123 mg every other day)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Cardiological evaluation</intervention_name>
    <description>Baseline evaluation&#xD;
FAbry STabilization indEX (FASTEX)&#xD;
12 leads ECG&#xD;
Blood samples for microRNA, TnT HS and NT-proBNP dosages&#xD;
2D echocardiogram&#xD;
Cardio-pulmonary test&#xD;
Contrast-enhanced CMR including:&#xD;
Cine images&#xD;
T2 mapping sequences&#xD;
T1 mapping sequences before and 15' after contrast medium administration&#xD;
Late Gadolinium Enhancement (LGE) imaging&#xD;
Phase contrast images (LVOT, aortic flow)&#xD;
Follow up evaluation&#xD;
•After 18 months, the same procedures will be repeated</description>
    <arm_group_label>Fabry Disease patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples for Troponin T, NT-proBNP and microRNA assay&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Between patients with genetic diagnosis of AFD referred for CMR at Policlinico San Donato,&#xD;
        15 patients with amenable mutation, clinical indication to Migalastat and signs of early or&#xD;
        overt cardiac involvement (low myocardial native T1 value ± left ventricular hypertrophy)&#xD;
        will be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Genetic diagnosis of Fabry Disease and amenable mutation&#xD;
&#xD;
          -  Clinical indication to Migalastat&#xD;
&#xD;
          -  Signs of clinical or preclinical cardiac involvement (low T1 values with or without&#xD;
             left ventricular hypertrophy)&#xD;
&#xD;
          -  Age &gt;16&#xD;
&#xD;
          -  Ability to give a complete informed consent (for minor patients informed consent will&#xD;
             be given by parents)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to Migalastat (pregnancy, age &lt;16, Glomerular Filtration Rate &lt;30&#xD;
             ml/min, hypersensitivity to the active ingredient)&#xD;
&#xD;
          -  Contraindication to CMR study (metallic fragment or foreign body, known&#xD;
             claustrophobia, PaceMaker/Implantable Cardioverter Defibrillator not CMR conditional,&#xD;
             electronic implant or device, eg, insulin pump or other infusion pump)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonia Camporeale, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Policlinico S. Donato</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS Policlinico San Donato</name>
      <address>
        <city>San Donato Milanese</city>
        <state>Milano</state>
        <zip>20097</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Hughes DA, Nicholls K, Shankar SP, Sunder-Plassmann G, Koeller D, Nedd K, Vockley G, Hamazaki T, Lachmann R, Ohashi T, Olivotto I, Sakai N, Deegan P, Dimmock D, Eyskens F, Germain DP, Goker-Alpan O, Hachulla E, Jovanovic A, Lourenco CM, Narita I, Thomas M, Wilcox WR, Bichet DG, Schiffmann R, Ludington E, Viereck C, Kirk J, Yu J, Johnson F, Boudes P, Benjamin ER, Lockhart DJ, Barlow C, Skuban N, Castelli JP, Barth J, Feldt-Rasmussen U. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet. 2017 Apr;54(4):288-296. doi: 10.1136/jmedgenet-2016-104178. Epub 2016 Nov 10. Erratum In: J Med Genet. 2018 Apr 16;:</citation>
    <PMID>27834756</PMID>
  </reference>
  <reference>
    <citation>Sado DM, White SK, Piechnik SK, Banypersad SM, Treibel T, Captur G, Fontana M, Maestrini V, Flett AS, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Neubauer S, Elliott PM, Moon JC. Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping. Circ Cardiovasc Imaging. 2013 May 1;6(3):392-8. doi: 10.1161/CIRCIMAGING.112.000070. Epub 2013 Apr 5.</citation>
    <PMID>23564562</PMID>
  </reference>
  <reference>
    <citation>Patel V, O'Mahony C, Hughes D, Rahman MS, Coats C, Murphy E, Lachmann R, Mehta A, Elliott PM. Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease. Heart. 2015 Jun;101(12):961-6. doi: 10.1136/heartjnl-2014-306782. Epub 2015 Feb 5.</citation>
    <PMID>25655062</PMID>
  </reference>
  <reference>
    <citation>Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007 Apr;93(4):528-35. doi: 10.1136/hrt.2005.063818. No abstract available.</citation>
    <PMID>17401074</PMID>
  </reference>
  <reference>
    <citation>Moon JC, Sheppard M, Reed E, Lee P, Elliott PM, Pennell DJ. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. J Cardiovasc Magn Reson. 2006;8(3):479-82. doi: 10.1080/10976640600605002.</citation>
    <PMID>16755835</PMID>
  </reference>
  <reference>
    <citation>Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ; International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001 Jul 5;345(1):9-16. doi: 10.1056/NEJM200107053450102.</citation>
    <PMID>11439963</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11386930</PMID>
  </reference>
  <reference>
    <citation>Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation. 2003 Sep 16;108(11):1299-301. doi: 10.1161/01.CIR.0000091253.71282.04. Epub 2003 Sep 2.</citation>
    <PMID>12952834</PMID>
  </reference>
  <reference>
    <citation>Imbriaco M, Pisani A, Spinelli L, Cuocolo A, Messalli G, Capuano E, Marmo M, Liuzzi R, Visciano B, Cianciaruso B, Salvatore M. Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study. Heart. 2009 Jul;95(13):1103-7. doi: 10.1136/hrt.2008.162800. Epub 2009 Apr 15.</citation>
    <PMID>19372091</PMID>
  </reference>
  <reference>
    <citation>Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, Beitner-Johnson D, Benistan K, Cabrera G, Charrow J, Kantola I, Linhart A, Nicholls K, Niemann M, Scott CR, Sims K, Waldek S, Warnock DG, Strotmann J; Fabry Registry. Analysis of left ventricular mass in untreated men and in men treated with agalsidase-beta: data from the Fabry Registry. Genet Med. 2013 Dec;15(12):958-65. doi: 10.1038/gim.2013.53. Epub 2013 May 23.</citation>
    <PMID>23703683</PMID>
  </reference>
  <reference>
    <citation>Beer M, Weidemann F, Breunig F, Knoll A, Koeppe S, Machann W, Hahn D, Wanner C, Strotmann J, Sandstede J. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy. Am J Cardiol. 2006 May 15;97(10):1515-8. doi: 10.1016/j.amjcard.2005.11.087. Epub 2006 Mar 29.</citation>
    <PMID>16679096</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25795794</PMID>
  </reference>
  <reference>
    <citation>Germain DP, Fan JQ. Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: in vitro and preclinical studies. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S111-7.</citation>
    <PMID>20040321</PMID>
  </reference>
  <reference>
    <citation>Johnson FK, Mudd PN Jr, Bragat A, Adera M, Boudes P. Pharmacokinetics and Safety of Migalastat HCl and Effects on Agalsidase Activity in Healthy Volunteers. Clin Pharmacol Drug Dev. 2013 Apr;2(2):120-32. doi: 10.1002/cpdd.1. Epub 2013 Feb 21.</citation>
    <PMID>27121667</PMID>
  </reference>
  <reference>
    <citation>Khanna R, Soska R, Lun Y, Feng J, Frascella M, Young B, Brignol N, Pellegrino L, Sitaraman SA, Desnick RJ, Benjamin ER, Lockhart DJ, Valenzano KJ. The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol Ther. 2010 Jan;18(1):23-33. doi: 10.1038/mt.2009.220. Epub 2009 Sep 22.</citation>
    <PMID>19773742</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>27509102</PMID>
  </reference>
  <reference>
    <citation>Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015 Jan;28(1):1-39.e14. doi: 10.1016/j.echo.2014.10.003.</citation>
    <PMID>25559473</PMID>
  </reference>
  <reference>
    <citation>Deva DP, Hanneman K, Li Q, Ng MY, Wasim S, Morel C, Iwanochko RM, Thavendiranathan P, Crean AM. Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease. J Cardiovasc Magn Reson. 2016 Mar 31;18:14. doi: 10.1186/s12968-016-0233-6.</citation>
    <PMID>27036375</PMID>
  </reference>
  <reference>
    <citation>Grothues F, Smith GC, Moon JC, Bellenger NG, Collins P, Klein HU, Pennell DJ. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002 Jul 1;90(1):29-34. doi: 10.1016/s0002-9149(02)02381-0.</citation>
    <PMID>12088775</PMID>
  </reference>
  <reference>
    <citation>Moon JC, Sachdev B, Elkington AG, McKenna WJ, Mehta A, Pennell DJ, Leed PJ, Elliott PM. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J. 2003 Dec;24(23):2151-5. doi: 10.1016/j.ehj.2003.09.017.</citation>
    <PMID>14643276</PMID>
  </reference>
  <reference>
    <citation>Koeppe S, Neubauer H, Breunig F, Weidemann F, Wanner C, Sandstede J, Machann W, Hahn D, Kostler H, Beer M. MR-based analysis of regional cardiac function in relation to cellular integrity in Fabry disease. Int J Cardiol. 2012 Sep 20;160(1):53-8. doi: 10.1016/j.ijcard.2011.03.023. Epub 2011 Apr 3.</citation>
    <PMID>21463907</PMID>
  </reference>
  <reference>
    <citation>Kramer J, Niemann M, Stork S, Frantz S, Beer M, Ertl G, Wanner C, Weidemann F. Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease. Am J Cardiol. 2014 Sep 15;114(6):895-900. doi: 10.1016/j.amjcard.2014.06.019. Epub 2014 Jul 2.</citation>
    <PMID>25073565</PMID>
  </reference>
  <reference>
    <citation>Kramer J, Niemann M, Liu D, Hu K, Machann W, Beer M, Wanner C, Ertl G, Weidemann F. Two-dimensional speckle tracking as a non-invasive tool for identification of myocardial fibrosis in Fabry disease. Eur Heart J. 2013 Jun;34(21):1587-96. doi: 10.1093/eurheartj/eht098. Epub 2013 Mar 21.</citation>
    <PMID>23520186</PMID>
  </reference>
  <reference>
    <citation>Bottomley PA, Foster TH, Argersinger RE, Pfeifer LM. A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1-100 MHz: dependence on tissue type, NMR frequency, temperature, species, excision, and age. Med Phys. 1984 Jul-Aug;11(4):425-48. doi: 10.1118/1.595535.</citation>
    <PMID>6482839</PMID>
  </reference>
  <reference>
    <citation>Pica S, Sado DM, Maestrini V, Fontana M, White SK, Treibel T, Captur G, Anderson S, Piechnik SK, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Kellman P, Elliott PM, Herrey AS, Moon JC. Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2014 Dec 5;16(1):99. doi: 10.1186/s12968-014-0099-4.</citation>
    <PMID>25475749</PMID>
  </reference>
  <reference>
    <citation>Thompson RB, Chow K, Khan A, Chan A, Shanks M, Paterson I, Oudit GY. T(1) mapping with cardiovascular MRI is highly sensitive for Fabry disease independent of hypertrophy and sex. Circ Cardiovasc Imaging. 2013 Sep;6(5):637-45. doi: 10.1161/CIRCIMAGING.113.000482. Epub 2013 Aug 6.</citation>
    <PMID>23922004</PMID>
  </reference>
  <reference>
    <citation>Pedrizzetti G, Claus P, Kilner PJ, Nagel E. Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use. J Cardiovasc Magn Reson. 2016 Aug 26;18(1):51. doi: 10.1186/s12968-016-0269-7.</citation>
    <PMID>27561421</PMID>
  </reference>
  <reference>
    <citation>Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010 Apr 2;106(6):1035-9. doi: 10.1161/CIRCRESAHA.110.218297. Epub 2010 Feb 25.</citation>
    <PMID>20185794</PMID>
  </reference>
  <reference>
    <citation>Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010 Sep 3;107(5):677-84. doi: 10.1161/CIRCRESAHA.109.215566. Epub 2010 Jul 1.</citation>
    <PMID>20595655</PMID>
  </reference>
  <reference>
    <citation>Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010 Sep 17;107(6):810-7. doi: 10.1161/CIRCRESAHA.110.226357. Epub 2010 Jul 22.</citation>
    <PMID>20651284</PMID>
  </reference>
  <reference>
    <citation>Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, Sinning JM, Vasa-Nicotera M, Nickenig G, Werner N. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc. 2014 Oct 27;3(6):e001249. doi: 10.1161/JAHA.114.001249.</citation>
    <PMID>25349183</PMID>
  </reference>
  <reference>
    <citation>Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012 Feb;14(2):147-54. doi: 10.1093/eurjhf/hfr155. Epub 2011 Nov 25.</citation>
    <PMID>22120965</PMID>
  </reference>
  <reference>
    <citation>Mignani R, Pieruzzi F, Berri F, Burlina A, Chinea B, Gallieni M, Pieroni M, Salviati A, Spada M. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease. Clin Kidney J. 2016 Oct;9(5):739-47. doi: 10.1093/ckj/sfw082. Epub 2016 Sep 9.</citation>
    <PMID>27679722</PMID>
  </reference>
  <reference>
    <citation>Cammarata G, Scalia S, Colomba P, Zizzo C, Pisani A, Riccio E, Montalbano M, Alessandro R, Giordano A, Duro G. A pilot study of circulating microRNAs as potential biomarkers of Fabry disease. Oncotarget. 2018 Jun 8;9(44):27333-27345. doi: 10.18632/oncotarget.25542. eCollection 2018 Jun 8.</citation>
    <PMID>29937989</PMID>
  </reference>
  <reference>
    <citation>Baig S, Edward NC, Kotecha D, Liu B, Nordin S, Kozor R, Moon JC, Geberhiwot T, Steeds RP. Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice. Europace. 2018 Sep 1;20(FI2):f153-f161. doi: 10.1093/europace/eux261.</citation>
    <PMID>29045633</PMID>
  </reference>
  <reference>
    <citation>Nordin S, Kozor R, Baig S, Abdel-Gadir A, Medina-Menacho K, Rosmini S, Captur G, Tchan M, Geberhiwot T, Murphy E, Lachmann R, Ramaswami U, Edwards NC, Hughes D, Steeds RP, Moon JC. Cardiac Phenotype of Prehypertrophic Fabry Disease. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007168. doi: 10.1161/CIRCIMAGING.117.007168.</citation>
    <PMID>29853467</PMID>
  </reference>
  <reference>
    <citation>Nordin S, Kozor R, Medina-Menacho K, Abdel-Gadir A, Baig S, Sado DM, Lobascio I, Murphy E, Lachmann RH, Mehta A, Edwards NC, Ramaswami U, Steeds RP, Hughes D, Moon JC. Proposed Stages of Myocardial Phenotype Development in Fabry Disease. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1673-1683. doi: 10.1016/j.jcmg.2018.03.020. Epub 2018 May 16.</citation>
    <PMID>29778854</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 10, 2019</study_first_submitted>
  <study_first_submitted_qc>February 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>March 17, 2021</last_update_submitted>
  <last_update_submitted_qc>March 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale San Donato</investigator_affiliation>
    <investigator_full_name>Antonia Camporeale</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Fabry Disease</keyword>
  <keyword>Migalastat</keyword>
  <keyword>Cardiomyopathy</keyword>
  <keyword>Cardiac Magnetic Resonance</keyword>
  <keyword>T1 mapping</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03838237
org study id: 148/int/2017
nct id: NCT03838237
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Anderson-Fabry Disease (AFD) is one of the rare lysosomal storage disorders for which a cause
      - specific therapy is available. Recently, a new specific drug has been marketed, namely
      Migalastat, a small-molecule pharmacological chaperone. The effect of Migalastat on cardiac
      involvement has been assessed so far by 2D echocardiography, demonstrating a significant
      reduction in left ventricular (LV) mass after 18 months of therapy. Calculation of LV mass by
      2D echocardiography is limited by geometrical assumptions and quality of echocardiographic
      window, with a strong impact on accuracy. Cardiac Magnetic Resonance (CMR) overcomes these
      limitations, thus representing the gold standard technique for ventricular mass, volumes and
      function estimation. Moreover, CMR offers the unique possibility to perform a non-invasive
      tissue characterization, including the detection of both myocardial fibrosis by Late
      Gadolinium Enhancement and sphingolipid storage by T1 mapping. Beyond an accurate
      morphological description and a detailed tissue characterization, a complete cardiological
      assessment should also integrate functional data and bio-humoral profile.

      This study is designed to provide a comprehensive evaluation of the therapeutic effect of
      Migalastat (123 mg every other day) on cardiac involvement after 18 months of therapy,
      integrating a morphological, functional and bio-humoral assessment.
Anderson-Fabry disease is a rare X-linked lysosomal disorder, mainly affecting
      cardiovascular, renal and nervous systems. Cardiac injury is the leading cause of death in
      these patients. Heart involvement is characterized by left ventricular hypertrophy (LVH),
      myocardial scarring and/or inflammation, Bradyarrhythmias or tachyarrhythmias, heart failure
      and represents the main cause of death in these patients. Since 2001, specific therapies
      (enzyme replacement therapy (ERT) first and pharmacological chaperone migalastat more
      recently) are available to treat these patients.

      Migalastat is a small-molecule pharmacological chaperone stabilizing speciﬁc mutant forms of
      the enzyme (α-Gal ) and promoting its catabolic function. These mutant forms of α-Gal are
      deﬁned as amenable to Migalastat. In patients with amenable mutations, orally administered
      Migalastat is a potential alternative treatment to intravenous ERT. Because of its chemical
      nature (small molecule) and route of administration (orally), Migalastat would avoid
      ERT-associated immunogenicity and infusion-associated reactions. Additionally, the higher
      volume of distribution of migalastat relative to ERT suggests enhanced penetration of organs
      and tissues. Theoretically, the chaperoning of α-Gal by Migalastat to lysosomes may better
      mimic natural enzyme trafficking and result in more constant α-Gal activity than biweekly ERT
      infusions.

      Two main clinical studies have been published so far about safety and efficacy of Migalastat
      in AFD, demonstrating good safety, tolerability and comparable efficacy to ERT. These studies
      reported a significant decrease in LV mass index assessed by 2D echocardiography (-6,6 g/m2
      in 33 patients after 18 months of therapy), mostly in patients with overt cardiac involvement
      and greater than the changes observed with ERT (-2 g/m2 in 16 patients after 18 months of
      therapy).

      Calculation of LV mass by 2D echocardiography is based on the "Devereux formula", assuming
      that the LV is a prolate ellipsoid with a 2:1 long/short axis ratio and symmetric
      distribution of hypertrophy. This is not always the case in AFD Cardiomyopathy, showing a
      wide variety of hypertrophy patterns. Moreover, since linear measurements of LV wall
      thickness and diameters are cubed in this formula, even small measurement errors in
      dimensions or thickness have a strong impact on accuracy.

      Cardiac magnetic resonance (CMR) represents the gold standard technique for ventricular mass,
      volumes and function estimation because of the possibility to directly measure these
      parameters without geometrical assumption. Therefore, CMR has an excellent inter-study
      reproducibility both in normal and in pathologic hearts, overcoming 2D echocardiography.
      Beyond its high reproducibility in LV mass measurement, CMR offers the unique possibility of
      non-invasive tissue characterization. This concept includes both detection and quantification
      of myocardial fibrosis by Late Gadolinium Enhancement images and application of new
      techniques, namely T1 mapping, detecting myocardial sphingolipid storage even before LVH
      occurs. Also, CMR allows a detailed characterization of myocardial deformation by feature
      tracking. Feature tracking CMR (FT-CMR) approximately applies the same principles of speckle
      tracking echocardiography (even though with differences methods of image acquisition and
      reconstruction) in order to measure global and segmental myocardial deformation. The strength
      of FT-CMR consists of its relatively unrestricted access to large fields of view, its high
      spatial resolution and its relatively high signal to noise and contrast to noise ratios.

      MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the
      post-transcriptional level. MiRNAs have emerged as key regulators of several physiological
      and pathophysiological processes. Besides their intracellular function, recent studies
      demonstrated that miRNAs can be exported or released by cells and circulate in blood in a
      remarkably stable form. The discovery of circulating miRNAs opens the possibilities to use
      circulating miRNA patterns as biomarkers for several pathologies also for cardiovascular
      diseases. In a recent study, a common microRNA signature in AFD patients regardless of gender
      and age has been identified.15 miRNAs differentially expressed between 10 AFD subjects and 10
      normal controls (NC) have been found. The levels of these 15 miRNAs in plasma sample of 10
      subjects with LVH and no mutation in the Galactosidase Alpha (GLA) gene have also been
      studied. Among these 15 miRNAs, 3 discriminated AFD patients from subjects with LVH. In
      particular, 2 microRNAs (mir-199a-5p and mir126a-3p) were up-regulated and 1 miRNA
      (mir-423-5p) was down-expressed in AFD patients. Interestingly, in a recent study increased
      plasmatic levels of miR-126 and miR-199a were significantly associated with a lower major
      adverse Cardiovascular (CV) event rate in patients with coronary artery disease. Instead,
      elevated plasmatic levels of mir-423-5p is strongly related to the clinical diagnosis of
      Heart Failure. Several evidences indicate that the aberrantly expressed plasmatic miRNAs in
      AFD are linked to microvascular or macrovascular damage involved in the typical AFD
      vasculopathy and could be attractive as diagnostic markers as well as for the monitoring of
      the pharmacological treatment.

      Integration of all these aspects allows a complete morpho-functional evaluation of cardiac
      involvement in AFD and a detailed monitoring of the effects of specific drugs.

      This study is designed to provide a comprehensive evaluation of the therapeutic effect of
      Migalastat on cardiac involvement, integrating a morphological, functional and bio-humoral
      assessment of heart involvement. 15 patients with amenable mutation, clinical indication to
      Migalastat and signs of early or overt cardiac involvement with will undergo a complete
      cardiological evaluation before and 18 months after therapy with Migalastat. The
      cardiological assessment will include ECG, 2D echocardiography, CMR, cardio-pulmonary test,
      dosage of peripheral biomarkers (TnT High Sensitive; NT-proBNP, mir-199a-5p and mir126a-3p,
      mir-423-5p).
observational model: Cohort
time perspective: Prospective
measure: Delta left ventricular mass
time frame: 18 months
description: Changes in left ventricular mass measured by cardiac magnetic resonance
measure: Delta native myocardial T1 values
time frame: 18 months
description: Changes in native myocardial T1 values measured by cardiac magnetic resonance
measure: Delta left ventricular global longitudinal strain
time frame: 18 months
description: Changes in left ventricular global longitudinal strain measured by cardiac magnetic resonance
measure: Delta 3 plasmatic microRNAs levels
time frame: 18 months
description: Changes in mir-199a-5p, mir126a-3p, mir-423-5p levels measured by Real-Time quantitative Polymerase Cycle Reaction (RT-qPCR)
arm group label: Fabry Disease patients
description: Patients with genetic diagnosis of Fabry Disease, clinical indication to Migalastat and signs of cardiac involvement (early or advanced) will undergo cardiological evaluation before and 18 months after therapy with Migalastat (123 mg every other day)
intervention type: Diagnostic Test
intervention name: Cardiological evaluation
description: Baseline evaluation
FAbry STabilization indEX (FASTEX)
12 leads ECG
Blood samples for microRNA, TnT HS and NT-proBNP dosages
2D echocardiogram
Cardio-pulmonary test
Contrast-enhanced CMR including:
Cine images
T2 mapping sequences
T1 mapping sequences before and 15' after contrast medium administration
Late Gadolinium Enhancement (LGE) imaging
Phase contrast images (LVOT, aortic flow)
Follow up evaluation
•After 18 months, the same procedures will be repeated
arm group label: Fabry Disease patients
Blood samples for Troponin T, NT-proBNP and microRNA assay
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Antonia Camporeale, MD, PhD
role: Principal Investigator
affiliation: IRCCS Policlinico S. Donato
facility: 
country: Italy
citation: Hughes DA, Nicholls K, Shankar SP, Sunder-Plassmann G, Koeller D, Nedd K, Vockley G, Hamazaki T, Lachmann R, Ohashi T, Olivotto I, Sakai N, Deegan P, Dimmock D, Eyskens F, Germain DP, Goker-Alpan O, Hachulla E, Jovanovic A, Lourenco CM, Narita I, Thomas M, Wilcox WR, Bichet DG, Schiffmann R, Ludington E, Viereck C, Kirk J, Yu J, Johnson F, Boudes P, Benjamin ER, Lockhart DJ, Barlow C, Skuban N, Castelli JP, Barth J, Feldt-Rasmussen U. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet. 2017 Apr;54(4):288-296. doi: 10.1136/jmedgenet-2016-104178. Epub 2016 Nov 10. Erratum In: J Med Genet. 2018 Apr 16;:
PMID: 27834756
citation: Sado DM, White SK, Piechnik SK, Banypersad SM, Treibel T, Captur G, Fontana M, Maestrini V, Flett AS, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Neubauer S, Elliott PM, Moon JC. Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping. Circ Cardiovasc Imaging. 2013 May 1;6(3):392-8. doi: 10.1161/CIRCIMAGING.112.000070. Epub 2013 Apr 5.
PMID: 23564562
citation: Patel V, O'Mahony C, Hughes D, Rahman MS, Coats C, Murphy E, Lachmann R, Mehta A, Elliott PM. Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease. Heart. 2015 Jun;101(12):961-6. doi: 10.1136/heartjnl-2014-306782. Epub 2015 Feb 5.
PMID: 25655062
citation: Linhart A, Elliott PM. The heart in Anderson-Fabry disease and other lysosomal storage disorders. Heart. 2007 Apr;93(4):528-35. doi: 10.1136/hrt.2005.063818. No abstract available.
PMID: 17401074
citation: Moon JC, Sheppard M, Reed E, Lee P, Elliott PM, Pennell DJ. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease. J Cardiovasc Magn Reson. 2006;8(3):479-82. doi: 10.1080/10976640600605002.
PMID: 16755835
citation: Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ; International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001 Jul 5;345(1):9-16. doi: 10.1056/NEJM200107053450102.
PMID: 11439963
citation: 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
citation: Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation. 2003 Sep 16;108(11):1299-301. doi: 10.1161/01.CIR.0000091253.71282.04. Epub 2003 Sep 2.
PMID: 12952834
citation: Imbriaco M, Pisani A, Spinelli L, Cuocolo A, Messalli G, Capuano E, Marmo M, Liuzzi R, Visciano B, Cianciaruso B, Salvatore M. Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study. Heart. 2009 Jul;95(13):1103-7. doi: 10.1136/hrt.2008.162800. Epub 2009 Apr 15.
PMID: 19372091
citation: Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, Beitner-Johnson D, Benistan K, Cabrera G, Charrow J, Kantola I, Linhart A, Nicholls K, Niemann M, Scott CR, Sims K, Waldek S, Warnock DG, Strotmann J; Fabry Registry. Analysis of left ventricular mass in untreated men and in men treated with agalsidase-beta: data from the Fabry Registry. Genet Med. 2013 Dec;15(12):958-65. doi: 10.1038/gim.2013.53. Epub 2013 May 23.
PMID: 23703683
citation: Beer M, Weidemann F, Breunig F, Knoll A, Koeppe S, Machann W, Hahn D, Wanner C, Strotmann J, Sandstede J. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy. Am J Cardiol. 2006 May 15;97(10):1515-8. doi: 10.1016/j.amjcard.2005.11.087. Epub 2006 Mar 29.
PMID: 16679096
citation: 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
citation: Germain DP, Fan JQ. Pharmacological chaperone therapy by active-site-specific chaperones in Fabry disease: in vitro and preclinical studies. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S111-7.
PMID: 20040321
citation: Johnson FK, Mudd PN Jr, Bragat A, Adera M, Boudes P. Pharmacokinetics and Safety of Migalastat HCl and Effects on Agalsidase Activity in Healthy Volunteers. Clin Pharmacol Drug Dev. 2013 Apr;2(2):120-32. doi: 10.1002/cpdd.1. Epub 2013 Feb 21.
PMID: 27121667
citation: Khanna R, Soska R, Lun Y, Feng J, Frascella M, Young B, Brignol N, Pellegrino L, Sitaraman SA, Desnick RJ, Benjamin ER, Lockhart DJ, Valenzano KJ. The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol Ther. 2010 Jan;18(1):23-33. doi: 10.1038/mt.2009.220. Epub 2009 Sep 22.
PMID: 19773742
citation: 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
citation: Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015 Jan;28(1):1-39.e14. doi: 10.1016/j.echo.2014.10.003.
PMID: 25559473
citation: Deva DP, Hanneman K, Li Q, Ng MY, Wasim S, Morel C, Iwanochko RM, Thavendiranathan P, Crean AM. Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease. J Cardiovasc Magn Reson. 2016 Mar 31;18:14. doi: 10.1186/s12968-016-0233-6.
PMID: 27036375
citation: Grothues F, Smith GC, Moon JC, Bellenger NG, Collins P, Klein HU, Pennell DJ. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002 Jul 1;90(1):29-34. doi: 10.1016/s0002-9149(02)02381-0.
PMID: 12088775
citation: Moon JC, Sachdev B, Elkington AG, McKenna WJ, Mehta A, Pennell DJ, Leed PJ, Elliott PM. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J. 2003 Dec;24(23):2151-5. doi: 10.1016/j.ehj.2003.09.017.
PMID: 14643276
citation: Koeppe S, Neubauer H, Breunig F, Weidemann F, Wanner C, Sandstede J, Machann W, Hahn D, Kostler H, Beer M. MR-based analysis of regional cardiac function in relation to cellular integrity in Fabry disease. Int J Cardiol. 2012 Sep 20;160(1):53-8. doi: 10.1016/j.ijcard.2011.03.023. Epub 2011 Apr 3.
PMID: 21463907
citation: Kramer J, Niemann M, Stork S, Frantz S, Beer M, Ertl G, Wanner C, Weidemann F. Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease. Am J Cardiol. 2014 Sep 15;114(6):895-900. doi: 10.1016/j.amjcard.2014.06.019. Epub 2014 Jul 2.
PMID: 25073565
citation: Kramer J, Niemann M, Liu D, Hu K, Machann W, Beer M, Wanner C, Ertl G, Weidemann F. Two-dimensional speckle tracking as a non-invasive tool for identification of myocardial fibrosis in Fabry disease. Eur Heart J. 2013 Jun;34(21):1587-96. doi: 10.1093/eurheartj/eht098. Epub 2013 Mar 21.
PMID: 23520186
citation: Bottomley PA, Foster TH, Argersinger RE, Pfeifer LM. A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms from 1-100 MHz: dependence on tissue type, NMR frequency, temperature, species, excision, and age. Med Phys. 1984 Jul-Aug;11(4):425-48. doi: 10.1118/1.595535.
PMID: 6482839
citation: Pica S, Sado DM, Maestrini V, Fontana M, White SK, Treibel T, Captur G, Anderson S, Piechnik SK, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Kellman P, Elliott PM, Herrey AS, Moon JC. Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2014 Dec 5;16(1):99. doi: 10.1186/s12968-014-0099-4.
PMID: 25475749
citation: Thompson RB, Chow K, Khan A, Chan A, Shanks M, Paterson I, Oudit GY. T(1) mapping with cardiovascular MRI is highly sensitive for Fabry disease independent of hypertrophy and sex. Circ Cardiovasc Imaging. 2013 Sep;6(5):637-45. doi: 10.1161/CIRCIMAGING.113.000482. Epub 2013 Aug 6.
PMID: 23922004
citation: Pedrizzetti G, Claus P, Kilner PJ, Nagel E. Principles of cardiovascular magnetic resonance feature tracking and echocardiographic speckle tracking for informed clinical use. J Cardiovasc Magn Reson. 2016 Aug 26;18(1):51. doi: 10.1186/s12968-016-0269-7.
PMID: 27561421
citation: Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010 Apr 2;106(6):1035-9. doi: 10.1161/CIRCRESAHA.110.218297. Epub 2010 Feb 25.
PMID: 20185794
citation: Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010 Sep 3;107(5):677-84. doi: 10.1161/CIRCRESAHA.109.215566. Epub 2010 Jul 1.
PMID: 20595655
citation: Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010 Sep 17;107(6):810-7. doi: 10.1161/CIRCRESAHA.110.226357. Epub 2010 Jul 22.
PMID: 20651284
citation: Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, Sinning JM, Vasa-Nicotera M, Nickenig G, Werner N. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc. 2014 Oct 27;3(6):e001249. doi: 10.1161/JAHA.114.001249.
PMID: 25349183
citation: Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012 Feb;14(2):147-54. doi: 10.1093/eurjhf/hfr155. Epub 2011 Nov 25.
PMID: 22120965
citation: Mignani R, Pieruzzi F, Berri F, Burlina A, Chinea B, Gallieni M, Pieroni M, Salviati A, Spada M. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease. Clin Kidney J. 2016 Oct;9(5):739-47. doi: 10.1093/ckj/sfw082. Epub 2016 Sep 9.
PMID: 27679722
citation: Cammarata G, Scalia S, Colomba P, Zizzo C, Pisani A, Riccio E, Montalbano M, Alessandro R, Giordano A, Duro G. A pilot study of circulating microRNAs as potential biomarkers of Fabry disease. Oncotarget. 2018 Jun 8;9(44):27333-27345. doi: 10.18632/oncotarget.25542. eCollection 2018 Jun 8.
PMID: 29937989
citation: Baig S, Edward NC, Kotecha D, Liu B, Nordin S, Kozor R, Moon JC, Geberhiwot T, Steeds RP. Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice. Europace. 2018 Sep 1;20(FI2):f153-f161. doi: 10.1093/europace/eux261.
PMID: 29045633
citation: Nordin S, Kozor R, Baig S, Abdel-Gadir A, Medina-Menacho K, Rosmini S, Captur G, Tchan M, Geberhiwot T, Murphy E, Lachmann R, Ramaswami U, Edwards NC, Hughes D, Steeds RP, Moon JC. Cardiac Phenotype of Prehypertrophic Fabry Disease. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007168. doi: 10.1161/CIRCIMAGING.117.007168.
PMID: 29853467
citation: Nordin S, Kozor R, Medina-Menacho K, Abdel-Gadir A, Baig S, Sado DM, Lobascio I, Murphy E, Lachmann RH, Mehta A, Edwards NC, Ramaswami U, Steeds RP, Hughes D, Moon JC. Proposed Stages of Myocardial Phenotype Development in Fabry Disease. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1673-1683. doi: 10.1016/j.jcmg.2018.03.020. Epub 2018 May 16.
PMID: 29778854
responsible party type: Principal Investigator
investigator affiliation: Ospedale San Donato
investigator full name: Antonia Camporeale
investigator title: MD, PhD
mesh term: Fabry Disease
mesh term: Heart Diseases