A Study to Evaluate Sildenafil for the Treatment of Lymphatic Malformations

NCT01290484 | Completed Phase 1 Results DMC

• 2 other identifiers: SU-10202010-7129UL1TR000093
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphangioma

Keywords

Lymphatic malformation, vascular malformation

Outcome Measures

Primary Outcomes (1)

• Change in Volume of Lymphatic Malformation

  Participants were given sildenafil for 20 weeks. Participants weighing more than 20 kg were given 20 mg 3 times daily (60 mg/day). Participants weighing between 8 kg and 20 kg were given 10 mg 3 times daily (30 mg/day).

  Baseline, 20 weeks

Study Arms (1)

Open Label

EXPERIMENTAL

Sildenafil oral tablet three times daily

Drug: Sildenafil

Interventions

Sildenafil DRUG

Sildenafil oral tablet three times daily

Also known as: Revatio, Viagra

Open Label

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• The participant weight is at least 8kg.
• 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.
• LMs may benefit from systemic therapy based on clinical criteria.
• Females must not be pregnant or breast-feeding.
• 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.
• Subject has no contraindication for use of sildenafil.
• LMs may involve any part of the body.
• Subject will have normal results on screening tests (eye exam, blood tests).
• Subject has no contraindication for MRI examinations, such as metal implants, etc.
• Subject must not be a smoker.

You may not qualify if:

• The participant has a medically unstable health status that may interfere with his/her ability to complete the study.
• 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).
• The participant requires concomitant use of potent cytochrome P450 3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, saquinavir) or concomitant use of ritonavir.
• The patient has had extensive prior surgery or sclerotherapy to treat LM such that scarring may interfere with the treatment effect of sildenafil.
• The participant has previously been administered treatment for LMs or surgical procedures have been performed to remove the index LMs.
• Participant is currently pregnant or considering becoming pregnant in the next 20 weeks.
• The participant is known to have an allergy to sildenafil.
• Ulcerated or currently infected LMs with pain.
• Diagnosis of the soft tissue tumor as LM is not clinically certain.
• The participant is participating in another clinical study.
• The participant has a history of priapism or is diagnosed with sickle cell anemia or any other disorder which may predispose to priapism.
• The investigator may declare any subject ineligible for a valid medical reason.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Danial C, Tichy AL, Tariq U, Swetman GL, Khuu P, Leung TH, Benjamin L, Teng J, Vasanawala SS, Lane AT. An open-label study to evaluate sildenafil for the treatment of lymphatic malformations. J Am Acad Dermatol. 2014 Jun;70(6):1050-7. doi: 10.1016/j.jaad.2014.02.005. Epub 2014 Mar 20.

  PMID: 24656411 RESULT

MeSH Terms

Conditions

Lymphangioma; Lymphatic Abnormalities; Vascular Malformations

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiovascular Abnormalities; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Baseline MRI examinations were performed within 6 months prior to commencement of sildenafil; several subjects took sildenafil for more than 20 weeks due to MRI scheduling and personal accommodations

Results Point of Contact

• Title: Dr. Alfred Lane
• Organization: Stanford University

alfred.lane@stanford.edu

650-721-7170

Study Officials

• Alfred T Lane, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Dermatology and of Pediatrics, Emeritus

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 7, 2011
• Study Start: December 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: December 1, 2013
• Last Updated: June 19, 2015
• Results First Posted: June 12, 2014

Record last verified: 2015-05

Locations

US (1)