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

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ClinicalTrials.gov Identifier: NCT03767660
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : December 6, 2018
Sponsor:
Collaborators:
Air Force General Hospital of the PLA
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Peking Union Medical College Hospital

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

Condition or disease Intervention/treatment Phase
Blue Rubber Bleb Nevus Syndrome Venous Malformation Drug: Rapamycin Phase 4

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Rapamycin (Sirolimus) in the Treatment of Blue Rubber Bleb Nevus Syndrome, Hereditary or Sporadic Venous Malformation
Actual Study Start Date : July 31, 2018
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : July 1, 2022


Arm Intervention/treatment
Experimental: Rapamycin
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
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
Other Name: Sirolimus




Primary Outcome Measures :
  1. Total venous malformation lesion load [ Time Frame: 30 days ]
    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.


Secondary Outcome Measures :
  1. Amount of daily oral iron supplements [ Time Frame: 1 day ]
    The value indicates the amount of gastrointestinal bleeding.

  2. Concentration of hemoglobin in blood [ Time Frame: 30 days ]
    The value indicates the amount of gastrointestinal bleeding.

  3. Frequency of blood transfusion [ Time Frame: 30 days ]
    The value indicates the amount of gastrointestinal bleeding

  4. Concentration of D-dimer in blood [ Time Frame: 30 days ]
    The value indicates the extent of local coagulation caused by Venous Malformation lesions.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Patients with poor recording (with incomplete, or inaccurate data)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767660


Contacts
Contact: Jiaolin Zhou, MD 13910136704 conniezhjl@yahoo.com

Locations
China, Beijing
Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences Recruiting
Beijing, Beijing, China, 100000
Contact: Jiaolin Zhou, MD    13910136704    conniezhjl@163.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Air Force General Hospital of the PLA
Chinese Academy of Medical Sciences
  Study Documents (Full-Text)

Documents provided by Peking Union Medical College Hospital:

Publications:

Responsible Party: Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03767660     History of Changes
Other Study ID Numbers: HS-1606
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peking Union Medical College Hospital:
Blue Rubber Bleb Nevus Syndrome
Venous Malformation
Rapamycin (sirolimus)
Mammalian target of rapamycin (mTOR) inhibitor
Treatment

Additional relevant MeSH terms:
Syndrome
Congenital Abnormalities
Gastrointestinal Neoplasms
Skin Neoplasms
Nevus, Blue
Disease
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Skin Diseases
Nevus, Pigmented
Nevus
Nevi and Melanomas
Neoplasms by Histologic Type
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs