Efficacy of Rapamycin (Sirolimus) in the Treatment of BRBNS, Hereditary or Sporadic Venous Malformation

NCT03767660 | Unknown Phase 4

• 1 other identifier: HS-1606
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Blue Rubber Bleb Nevus Syndrome; Venous Malformation

Keywords

Blue Rubber Bleb Nevus Syndrome; Venous Malformation; Rapamycin (sirolimus); Mammalian target of rapamycin (mTOR) inhibitor; Treatment

Outcome Measures

Primary Outcomes (1)

• Total venous malformation lesion load

  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.

  The time from start of therapy to 1 year

Secondary Outcomes (4)

• Amount of daily oral iron supplements

  The time from start of therapy to 1 year

• Concentration of hemoglobin in blood

  The time from start of therapy to 1 year

• Frequency of blood transfusion

  The time from start of therapy to 1 year

• Concentration of D-dimer in blood

  The time from start of therapy to 1 year

Study Arms (1)

Rapamycin

EXPERIMENTAL

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

Drug: Rapamycin

Interventions

Rapamycin DRUG

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

Also known as: Sirolimus

Rapamycin

Eligibility Criteria

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

You may qualify if:

• Patients diagnosed with BRBNS, VMCM, sporadic multiple VM, or large single VM;
• Age and gender are not limited;
• Physical status ECOG 0\~3;
• Organ function is good, biochemical examination meets the following conditions: AST ≤ 2.5 × upper limit of normal value (ULN), ALT ≤ 2.5 × upper limit of normal value (ULN), serum total bilirubin ≤ 1.5 × upper limit of normal value (ULN), creatinine ≤ 1.5 × upper limit of normal (ULN);
• Patients volunteer to participate in the trial and sign the informed consent form by the participant or his/her legal guardian.

You may not qualify if:

• Patients need emergency surgery due to intestinal obstruction, intussusception, or gastrointestinal bleeding;
• History of surgery within 1 month;
• allergic to rapamycin;
• Any disease or condition that may affect the study implementation or result interpretation, including: known hemoglobinopathy, suffering from gastrointestinal infections at the same time, severe heart, liver, kidney and other serious concomitant diseases that may endanger lives
• Pregnant or lactating women;
• Alcohol or drugs (eg, laxatives) abusers;
• Participating in another clinical trial that may affect this study within one month;
• Being believed not suitable to be enrolled by the investigator for other reasons.
• Exit Criteria:
• An allergic reaction to rapamycin occurs.
• The patient requests withdrawal: at his own discretion or at the request of his legal representative. Subjects may refuse to participate in further studies at any time without reasons. Subjects will not be affected because of such decision.
• Subjects are required to withdraw from the study in certain special circumstances (eg, there is significant issues of compliance, safety, or surgical intervention for the disease)
• Other situations in which the study must be terminated. For example, the investigators believe that continuing the study may be harmful to the health of subjects.
• Rejection Criteria:
• Patients who violate the requirements of the test protocol

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Air Force General Hospital of the PLA: collaborator
• Chinese Academy of Medical Sciences: collaborator

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Beijing, Beijing Municipality, 100000, China

RECRUITING

Related Publications (17)

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  PMID: 27519652 BACKGROUND

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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MeSH Terms

Conditions

Blue rubber bleb nevus syndrome; Hereditary Sensory and Autonomic Neuropathies

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Jiaolin Zhou, MD

CONTACT

13910136704; conniezhjl@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2018
• First Posted: December 6, 2018
• Study Start: July 31, 2018
• Primary Completion: January 1, 2022
• Study Completion: July 1, 2022
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

CN (1)