A Study to Evaluate Sildenafil for the Treatment of Lymphatic Malformations

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alfred Lane, Stanford University
ClinicalTrials.gov Identifier:
NCT01290484
First received: February 3, 2011
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

There is an unsatisfied medical need for a first-line treatment of lymphatic malformations with a good benefit/risk profile. Based on a patient experience in the institution, the investigators plan to verify whether or not the medication sildenafil has a beneficial effect on lymphatic malformations. The investigators plan to do this by treating patients with lymphatic malformations with the medication sildenafil for a 20 week period. This is an investigator initiated study funded by an Innovations in Patient Care grant and a SPARK grant.


Condition Intervention Phase
Lymphangioma
Drug: Sildenafil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Investigational Pilot Study to Evaluate Sildenafil for the Treatment of Lymphatic Malformations

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Change in lymphatic malformation size [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical lesion measurements [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]
  • Physician and participant assessments of lesional change from baseline [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: December 2010
Study Completion Date: December 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sildenafil
    Sildenafil oral tablet three times daily
  Eligibility

Ages Eligible for Study:   6 Months to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent(s) for study participation and (where applicable) the use of the participant's images are obtained according to national regulations from the participant's parent(s) or guardian(s) prior to performing any study procedures.
  2. The participant is 6 months to 10 years of age at inclusion.
  3. The participant weight is at least 8kg.
  4. A diagnosis of LM or mixed venous lymphatic malformation involving the skin and subcutaneous tissue and at least 3cm based on clinical and radiographic criteria.
  5. LMs may benefit from systemic therapy based on clinical criteria.
  6. Females must not be pregnant or breast-feeding.
  7. If participant is a child, parent/guardian must be able to follow instructions and must be willing and able to ensure that the subject is present for all required study visits.
  8. Subject has no contraindication for use of sildenafil.
  9. LMs may involve any part of the body.
  10. Subject will have normal results on screening tests (eye exam, blood tests).
  11. Subject has no contraindication for MRI examinations, such as metal implants, etc.
  12. Subject must not be a smoker.

Exclusion Criteria:

  1. The participant has a medically unstable health status that may interfere with his/her ability to complete the study.
  2. The participant presents with one or more of the following medical conditions: hepatic impairment; severe renal impairment; lymphedema conditions such as Milroy disease, Meige lymphedema, Hennekam syndrome, Njolstad syndrome, Aagenaes syndrome, and Fabry disease; hypotension or at risk for hypotension; seizures or history of seizures; any significant cardiovascular risk factors and any condition which requires participants to use nitric oxide donors or nitrates in any form; underlying anatomic or vascular risk factors for developing non-arteritic anterior ischemic optic neuropathy (NAION) including low ocular cup to disc ratio, age over 10, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. (Participants with Down syndrome, Turner syndrome, and Noonan syndrome will be considered on a case-by-case basis).
  3. The participant has received at least one of the following medications contraindicated in association with sildenafil within 15 days of inclusion: Alprostadil, Azole antifungals, Clarithromycins, Conivaptan, Delavirdine, Erythromycins, Fluvoxamine, Grapefruit, Imatinib, Nefazodone, Nitrates/sodium thiosulfate, Non-selective and selective alpha blockers, Protease inhibitors, Rufinamide, Tadalafil, Telithromycin, Vardenafil, Yohimbe, Yohimbine, Amifostine, Lapatinib, Warfarin
  4. The participant requires concomitant use of potent cytochrome P450 3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, saquinavir) or concomitant use of ritonavir.
  5. The patient has had extensive prior surgery or sclerotherapy to treat LM such that scarring may interfere with the treatment effect of sildenafil.
  6. The participant has previously been administered treatment for LMs or surgical procedures have been performed to remove the index LMs.
  7. Participant is currently pregnant or considering becoming pregnant in the next 20 weeks.
  8. The participant is known to have an allergy to sildenafil.
  9. Ulcerated or currently infected LMs with pain.
  10. Diagnosis of the soft tissue tumor as LM is not clinically certain.
  11. The participant is participating in another clinical study.
  12. The participant has a history of priapism or is diagnosed with sickle cell anemia or any other disorder which may predispose to priapism.
  13. The investigator may declare any subject ineligible for a valid medical reason.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01290484

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Alfred T Lane, MD Stanford University
  More Information

No publications provided

Responsible Party: Alfred Lane, Professor of Dermatology and Pediatrics, Stanford University
ClinicalTrials.gov Identifier: NCT01290484     History of Changes
Other Study ID Numbers: SU-10202010-7129, eProtocol #17893
Study First Received: February 3, 2011
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Stanford University:
Lymphatic malformation, mixed venous-lymphatic malformation, vascular malformation

Additional relevant MeSH terms:
Congenital Abnormalities
Lymphangioma
Lymphatic Abnormalities
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014