<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/NCT03767660</url>
  </required_header>
  <id_info>
    <org_study_id>HS-1606</org_study_id>
    <nct_id>NCT03767660</nct_id>
  </id_info>
  <brief_title>Efficacy of Rapamycin (Sirolimus) in the Treatment of BRBNS, Hereditary or Sporadic Venous Malformation</brief_title>
  <official_title>Efficacy of Rapamycin (Sirolimus) in the Treatment of Blue Rubber Bleb Nevus Syndrome, Hereditary or Sporadic Venous Malformation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Air Force General Hospital of the PLA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, nonrandomized, open-label, single-arm clinical trial to study efficacy of&#xD;
      rapamycin (sirolimus) in the treatment of Blue Rubber Bleb Nevus Syndrome, hereditary or&#xD;
      sporadic venous malformation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Blue rubber bleb nevus syndrome (BRBNS) and venous malformation are mainly caused by somatic&#xD;
      mutation of TEK and PIK3CA, which activates the PI3K/AKT signaling pathway. As an important&#xD;
      protein kinase downstream of the PI3K/AKT pathway, mTOR can serve as a potential therapeutic&#xD;
      target for BRBNS. Experiments of mice have shown that rapamycin inhibited the progression of&#xD;
      venous malformation lesions. There are a few human cases reported using rapamycin treatment.&#xD;
      The investigator's study is designed to be a prospective, nonrandomized, open-label,&#xD;
      single-arm clinical trial to investigate its efficacy and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 31, 2018</start_date>
  <completion_date type="Anticipated">July 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total venous malformation lesion load</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>lesion load (cm2) = A + B + C. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by chest, abdomen and pelvis MRI or small bowel CT reconstruction (in cm2) B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2) C = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by ultrasound (in cm2) Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Amount of daily oral iron supplements</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the amount of gastrointestinal bleeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of hemoglobin in blood</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the amount of gastrointestinal bleeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of blood transfusion</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the amount of gastrointestinal bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of D-dimer in blood</measure>
    <time_frame>The time from start of therapy to 1 year</time_frame>
    <description>The value indicates the extent of local coagulation caused by Venous Malformation lesions.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Blue Rubber Bleb Nevus Syndrome</condition>
  <condition>Venous Malformation</condition>
  <arm_group>
    <arm_group_label>Rapamycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapamycin</intervention_name>
    <description>For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months</description>
    <arm_group_label>Rapamycin</arm_group_label>
    <other_name>Sirolimus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with BRBNS, VMCM, sporadic multiple VM, or large single VM;&#xD;
&#xD;
          -  Age and gender are not limited;&#xD;
&#xD;
          -  Physical status ECOG 0~3;&#xD;
&#xD;
          -  Organ function is good, biochemical examination meets the following conditions: AST ≤&#xD;
             2.5 × upper limit of normal value (ULN), ALT ≤ 2.5 × upper limit of normal value&#xD;
             (ULN), serum total bilirubin ≤ 1.5 × upper limit of normal value (ULN), creatinine ≤&#xD;
             1.5 × upper limit of normal (ULN);&#xD;
&#xD;
          -  Patients volunteer to participate in the trial and sign the informed consent form by&#xD;
             the participant or his/her legal guardian.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients need emergency surgery due to intestinal obstruction, intussusception, or&#xD;
             gastrointestinal bleeding;&#xD;
&#xD;
          -  History of surgery within 1 month;&#xD;
&#xD;
          -  allergic to rapamycin;&#xD;
&#xD;
          -  Any disease or condition that may affect the study implementation or result&#xD;
             interpretation, including: known hemoglobinopathy, suffering from gastrointestinal&#xD;
             infections at the same time, severe heart, liver, kidney and other serious concomitant&#xD;
             diseases that may endanger lives&#xD;
&#xD;
          -  Pregnant or lactating women;&#xD;
&#xD;
          -  Alcohol or drugs (eg, laxatives) abusers;&#xD;
&#xD;
          -  Participating in another clinical trial that may affect this study within one month;&#xD;
&#xD;
          -  Being believed not suitable to be enrolled by the investigator for other reasons.&#xD;
&#xD;
        Exit Criteria:&#xD;
&#xD;
          -  An allergic reaction to rapamycin occurs.&#xD;
&#xD;
          -  The patient requests withdrawal: at his own discretion or at the request of his legal&#xD;
             representative. Subjects may refuse to participate in further studies at any time&#xD;
             without reasons. Subjects will not be affected because of such decision.&#xD;
&#xD;
          -  Subjects are required to withdraw from the study in certain special circumstances (eg,&#xD;
             there is significant issues of compliance, safety, or surgical intervention for the&#xD;
             disease)&#xD;
&#xD;
          -  Other situations in which the study must be terminated. For example, the investigators&#xD;
             believe that continuing the study may be harmful to the health of subjects.&#xD;
&#xD;
        Rejection Criteria:&#xD;
&#xD;
          -  Patients who violate the requirements of the test protocol&#xD;
&#xD;
          -  Patients with poor recording (with incomplete, or inaccurate data)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jiaolin Zhou, MD</last_name>
    <phone>13910136704</phone>
    <email>conniezhjl@yahoo.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiaolin Zhou, MD</last_name>
      <phone>13910136704</phone>
      <email>conniezhjl@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Soblet J, Kangas J, Natynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Leaute-Labreze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9.</citation>
    <PMID>27519652</PMID>
  </reference>
  <reference>
    <citation>Ochiai D, Miyakoshi K, Yakubo K, Fukuiya T, Yoshimura Y. Familial blue rubber bleb nevus syndrome in pregnancy with spinal epidural involvement. Case Rep Obstet Gynecol. 2013;2013:141506. doi: 10.1155/2013/141506. Epub 2013 May 9.</citation>
    <PMID>23762681</PMID>
  </reference>
  <reference>
    <citation>Carvalho S, Barbosa V, Santos N, Machado E. Blue rubber-bleb nevus syndrome: report of a familial case with a dural arteriovenous fistula. AJNR Am J Neuroradiol. 2003 Oct;24(9):1916-8.</citation>
    <PMID>14561629</PMID>
  </reference>
  <reference>
    <citation>Kisu T, Yamaoka K, Uchida Y, Mori H, Nakama T, Hisatsugu T, Miyaji H, Motooka M. A case of blue rubber bleb nevus syndrome with familial onset. Gastroenterol Jpn. 1986 Jun;21(3):262-6. doi: 10.1007/BF02774569.</citation>
    <PMID>3732758</PMID>
  </reference>
  <reference>
    <citation>Jin XL, Wang ZH, Xiao XB, Huang LS, Zhao XY. Blue rubber bleb nevus syndrome: a case report and literature review. World J Gastroenterol. 2014 Dec 7;20(45):17254-9. doi: 10.3748/wjg.v20.i45.17254.</citation>
    <PMID>25493043</PMID>
  </reference>
  <reference>
    <citation>Dobru D, Seuchea N, Dorin M, Careianu V. Blue rubber bleb nevus syndrome: case report and literature review. Rom J Gastroenterol. 2004 Sep;13(3):237-40.</citation>
    <PMID>15470538</PMID>
  </reference>
  <reference>
    <citation>Boscolo E, Limaye N, Huang L, Kang KT, Soblet J, Uebelhoer M, Mendola A, Natynki M, Seront E, Dupont S, Hammer J, Legrand C, Brugnara C, Eklund L, Vikkula M, Bischoff J, Boon LM. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest. 2015 Sep;125(9):3491-504. doi: 10.1172/JCI76004. Epub 2015 Aug 10.</citation>
    <PMID>26258417</PMID>
  </reference>
  <reference>
    <citation>Cardoso H, Dias JA, Silva M, Vilas-Boas F, Trindade E, Tavares M, Macedo G. 'Education and Imaging. Gastrointestinal: Successful treatment with sirolimus of a patient with blue rubber bleb nevus syndrome. J Gastroenterol Hepatol. 2016 Mar;31(3):519. doi: 10.1111/jgh.13178. No abstract available.</citation>
    <PMID>26456887</PMID>
  </reference>
  <reference>
    <citation>Yuksekkaya H, Ozbek O, Keser M, Toy H. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics. 2012 Apr;129(4):e1080-4. doi: 10.1542/peds.2010-3611. Epub 2012 Mar 5.</citation>
    <PMID>22392180</PMID>
  </reference>
  <reference>
    <citation>Unlusoy Aksu A, Sari S, Egritas Gurkan O, Dalgic B. Favorable Response to Sirolimus in a Child With Blue Rubber Bleb Nevus Syndrome in the Gastrointestinal Tract. J Pediatr Hematol Oncol. 2017 Mar;39(2):147-149. doi: 10.1097/MPH.0000000000000681.</citation>
    <PMID>27820137</PMID>
  </reference>
  <reference>
    <citation>Salloum R, Fox CE, Alvarez-Allende CR, Hammill AM, Dasgupta R, Dickie BH, Mobberley-Schuman P, Wentzel MS, Chute C, Kaul A, Patel M, Merrow AC, Gupta A, Whitworth JR, Adams DM. Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment. Pediatr Blood Cancer. 2016 Nov;63(11):1911-4. doi: 10.1002/pbc.26049. Epub 2016 Jun 8.</citation>
    <PMID>27273326</PMID>
  </reference>
  <reference>
    <citation>Moavero R, Coniglio A, Garaci F, Curatolo P. Is mTOR inhibition a systemic treatment for tuberous sclerosis? Ital J Pediatr. 2013 Sep 17;39:57. doi: 10.1186/1824-7288-39-57.</citation>
    <PMID>24044547</PMID>
  </reference>
  <reference>
    <citation>McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.</citation>
    <PMID>21410393</PMID>
  </reference>
  <reference>
    <citation>Paul E, Thiele E. Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):190-2. doi: 10.1056/NEJMe0707153. No abstract available.</citation>
    <PMID>18184966</PMID>
  </reference>
  <reference>
    <citation>Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):140-51. doi: 10.1056/NEJMoa063564.</citation>
    <PMID>18184959</PMID>
  </reference>
  <reference>
    <citation>Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.</citation>
    <PMID>21525172</PMID>
  </reference>
  <reference>
    <citation>Davies DM, Johnson SR, Tattersfield AE, Kingswood JC, Cox JA, McCartney DL, Doyle T, Elmslie F, Saggar A, de Vries PJ, Sampson JR. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):200-3. doi: 10.1056/NEJMc072500. No abstract available.</citation>
    <PMID>18184971</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 24, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>December 17, 2018</last_update_submitted>
  <last_update_submitted_qc>December 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Blue Rubber Bleb Nevus Syndrome</keyword>
  <keyword>Venous Malformation</keyword>
  <keyword>Rapamycin (sirolimus)</keyword>
  <keyword>Mammalian target of rapamycin (mTOR) inhibitor</keyword>
  <keyword>Treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
    <mesh_term>Nevus, Blue</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03767660/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03767660
org study id: HS-1606
nct id: NCT03767660
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
A prospective, nonrandomized, open-label, single-arm clinical trial to study efficacy of
      rapamycin (sirolimus) in the treatment of Blue Rubber Bleb Nevus Syndrome, hereditary or
      sporadic venous malformation
Blue rubber bleb nevus syndrome (BRBNS) and venous malformation are mainly caused by somatic
      mutation of TEK and PIK3CA, which activates the PI3K/AKT signaling pathway. As an important
      protein kinase downstream of the PI3K/AKT pathway, mTOR can serve as a potential therapeutic
      target for BRBNS. Experiments of mice have shown that rapamycin inhibited the progression of
      venous malformation lesions. There are a few human cases reported using rapamycin treatment.
      The investigator's study is designed to be a prospective, nonrandomized, open-label,
      single-arm clinical trial to investigate its efficacy and safety.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total venous malformation lesion load
time frame: The time from start of therapy to 1 year
description: lesion load (cm2) = A + B + C. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by chest, abdomen and pelvis MRI or small bowel CT reconstruction (in cm2) B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2) C = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by ultrasound (in cm2) Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.
measure: Amount of daily oral iron supplements
time frame: The time from start of therapy to 1 year
description: The value indicates the amount of gastrointestinal bleeding.
measure: Concentration of hemoglobin in blood
time frame: The time from start of therapy to 1 year
description: The value indicates the amount of gastrointestinal bleeding.
measure: Frequency of blood transfusion
time frame: The time from start of therapy to 1 year
description: The value indicates the amount of gastrointestinal bleeding
measure: Concentration of D-dimer in blood
time frame: The time from start of therapy to 1 year
description: The value indicates the extent of local coagulation caused by Venous Malformation lesions.
arm group label: Rapamycin
arm group type: Experimental
description: For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months
intervention type: Drug
intervention name: Rapamycin
description: For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months
arm group label: Rapamycin
other name: Sirolimus
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jiaolin Zhou, MD
phone: 13910136704
email: conniezhjl@yahoo.com
facility: 
status: Recruiting
contact: 
country: China
citation: Soblet J, Kangas J, Natynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Leaute-Labreze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9.
PMID: 27519652
citation: Ochiai D, Miyakoshi K, Yakubo K, Fukuiya T, Yoshimura Y. Familial blue rubber bleb nevus syndrome in pregnancy with spinal epidural involvement. Case Rep Obstet Gynecol. 2013;2013:141506. doi: 10.1155/2013/141506. Epub 2013 May 9.
PMID: 23762681
citation: Carvalho S, Barbosa V, Santos N, Machado E. Blue rubber-bleb nevus syndrome: report of a familial case with a dural arteriovenous fistula. AJNR Am J Neuroradiol. 2003 Oct;24(9):1916-8.
PMID: 14561629
citation: Kisu T, Yamaoka K, Uchida Y, Mori H, Nakama T, Hisatsugu T, Miyaji H, Motooka M. A case of blue rubber bleb nevus syndrome with familial onset. Gastroenterol Jpn. 1986 Jun;21(3):262-6. doi: 10.1007/BF02774569.
PMID: 3732758
citation: Jin XL, Wang ZH, Xiao XB, Huang LS, Zhao XY. Blue rubber bleb nevus syndrome: a case report and literature review. World J Gastroenterol. 2014 Dec 7;20(45):17254-9. doi: 10.3748/wjg.v20.i45.17254.
PMID: 25493043
citation: Dobru D, Seuchea N, Dorin M, Careianu V. Blue rubber bleb nevus syndrome: case report and literature review. Rom J Gastroenterol. 2004 Sep;13(3):237-40.
PMID: 15470538
citation: Boscolo E, Limaye N, Huang L, Kang KT, Soblet J, Uebelhoer M, Mendola A, Natynki M, Seront E, Dupont S, Hammer J, Legrand C, Brugnara C, Eklund L, Vikkula M, Bischoff J, Boon LM. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest. 2015 Sep;125(9):3491-504. doi: 10.1172/JCI76004. Epub 2015 Aug 10.
PMID: 26258417
citation: Cardoso H, Dias JA, Silva M, Vilas-Boas F, Trindade E, Tavares M, Macedo G. 'Education and Imaging. Gastrointestinal: Successful treatment with sirolimus of a patient with blue rubber bleb nevus syndrome. J Gastroenterol Hepatol. 2016 Mar;31(3):519. doi: 10.1111/jgh.13178. No abstract available.
PMID: 26456887
citation: Yuksekkaya H, Ozbek O, Keser M, Toy H. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics. 2012 Apr;129(4):e1080-4. doi: 10.1542/peds.2010-3611. Epub 2012 Mar 5.
PMID: 22392180
citation: Unlusoy Aksu A, Sari S, Egritas Gurkan O, Dalgic B. Favorable Response to Sirolimus in a Child With Blue Rubber Bleb Nevus Syndrome in the Gastrointestinal Tract. J Pediatr Hematol Oncol. 2017 Mar;39(2):147-149. doi: 10.1097/MPH.0000000000000681.
PMID: 27820137
citation: Salloum R, Fox CE, Alvarez-Allende CR, Hammill AM, Dasgupta R, Dickie BH, Mobberley-Schuman P, Wentzel MS, Chute C, Kaul A, Patel M, Merrow AC, Gupta A, Whitworth JR, Adams DM. Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment. Pediatr Blood Cancer. 2016 Nov;63(11):1911-4. doi: 10.1002/pbc.26049. Epub 2016 Jun 8.
PMID: 27273326
citation: Moavero R, Coniglio A, Garaci F, Curatolo P. Is mTOR inhibition a systemic treatment for tuberous sclerosis? Ital J Pediatr. 2013 Sep 17;39:57. doi: 10.1186/1824-7288-39-57.
PMID: 24044547
citation: McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.
PMID: 21410393
citation: Paul E, Thiele E. Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):190-2. doi: 10.1056/NEJMe0707153. No abstract available.
PMID: 18184966
citation: Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):140-51. doi: 10.1056/NEJMoa063564.
PMID: 18184959
citation: Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.
PMID: 21525172
citation: Davies DM, Johnson SR, Tattersfield AE, Kingswood JC, Cox JA, McCartney DL, Doyle T, Elmslie F, Saggar A, de Vries PJ, Sampson JR. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):200-3. doi: 10.1056/NEJMc072500. No abstract available.
PMID: 18184971
responsible party type: Sponsor
mesh term: Gastrointestinal Neoplasms
mesh term: Skin Neoplasms
mesh term: Nevus, Blue
mesh term: Congenital Abnormalities
mesh term: Syndrome
mesh term: Sirolimus
provided document: 