Pulsed-dye Laser vs. Topical Timolol for Hemangioma

Recruiting in Palo Alto (17 mi)

Overseen by R. Rox Anderson, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Beta-blockers, Ace inhibitors

Disqualifiers: Asthma, Cardiovascular disease, Immunocompromised, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if pulsed dye laser treatment or timolol maleate 0.5% gel can help infants who have a hemangioma. The investigators also want to find out if pulsed dye laser treatment and timolol maleate 0.5% gel are safe to use without causing too many side effects. Hemangioma is a common type of birthmark. These birthmarks happen when many new blood vessels grow in a specific area on the skin. Blood vessels are tiny tubes that carry blood through the body. No one knows what causes blood vessels to group together. Most birthmarks don't hurt at all and they usually aren't a sign of any kind of illness. Lots of newborns have these birthmarks on their bodies, like between the eyebrows. These birthmarks usually disappear within the first few months to years of life. These birthmarks tend to disappear spontaneously. Most hemangiomas are not treated unless the hemangioma threatens the child's health, which occurs in about 1 in 3 children with hemagiomas. Pulsed dye laser is widely used in children, and is approved by the U.S. Food and Drug Administration (FDA) for treating hemangioma. The FDA has approved timolol maleate to treat glaucoma in adults, but the FDA has not approved timolol maleate to treat hemangiomas in children. About 7 infants with hemangiomas have received timolol maleate. The results so far show that timolol maleate may be helpful and safe in treating hemangiomas in infants. An important question being tested in this study is whether pulsed-dye laser or timolol maleate can prevent hemangioma from growing when used very early after birth.

Will I have to stop taking my current medications?

The trial requires that participants do not use any other topical or oral treatments for the hemangioma besides those prescribed by the study investigators. If your infant is already on other treatments for hemangioma, they would not be eligible to participate.

What data supports the effectiveness of the treatment Pulsed-dye Laser vs. Topical Timolol for Hemangioma?

Research shows that both pulsed-dye laser and topical timolol are effective in treating infantile hemangiomas, with the laser often providing better results for mixed hemangiomas due to its ability to reach deeper blood vessels. Timolol is a safe alternative, especially for superficial hemangiomas, and combining it with laser treatment can enhance effectiveness. ^{1 2 3 4 5}

Is the combination of pulsed-dye laser and topical timolol safe for treating hemangiomas?

Studies show that both pulsed-dye laser and topical timolol are generally safe for treating infantile hemangiomas, with no significant side effects reported in the research. These treatments have been used successfully in many cases without causing harm. ^{1 2 3 4 6}

How does the treatment of pulsed-dye laser and topical timolol for hemangioma differ from other treatments?

The combination of pulsed-dye laser and topical timolol for treating hemangiomas is unique because it combines a laser that targets blood vessels with a topical beta-blocker that reduces blood flow, offering a non-invasive alternative to oral medications with fewer side effects. This approach is particularly effective for superficial hemangiomas and provides a safer option compared to systemic treatments. ^{1 2 3 4 7}

Research Team

R. Rox Anderson, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for infants under 3 months old with a type of birthmark called hemangioma that appeared shortly after birth. The child must not have received any prior treatments, and the parents/guardians must agree to follow the study's treatment plan and care requirements.

Inclusion Criteria

The birthmark is very small or not visible.

Willingness of parent/guardian to follow the treatment schedule and post treatment care requirements

My condition became noticeable within a month after birth.

Exclusion Criteria

You have a weakened immune system.

The area to be treated has scarring or infection.

I have asthma, COPD, heart issues, or am allergic to timolol. I also take beta-blockers or ACE inhibitors.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Infants receive either pulsed dye laser treatments weekly to semi-weekly for up to 6 treatments, or twice daily topical application of timolol for up to six months

6 weeks to 6 months

Weekly to semi-weekly visits for laser treatment, or regular follow-ups for timolol application

Follow-up

Participants are monitored for safety, effectiveness, and need for additional treatments after the initial treatment phase

2 years

Regular follow-up visits

Treatment Details

Interventions

• Observation (Other)
• Pulsed-dye Laser (Procedure)
• Topical Timolol Maleate (Beta Blocker)

Trial Overview The study tests if pulsed dye laser or timolol maleate gel can prevent the growth of hemangiomas in newborns. It compares these treatments against no intervention to see which is more effective and safe for treating these birthmarks early on.

Participant Groups

Group I: Topical Timolol Experimental Treatment 1 Intervention

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the timolol arm will receive twice daily topical application of a physician-specified amount of timolol maleate 0.5% ophthalmic solution (hereby referred to as topical timolol) for up to six months.

Group II: Pulsed Dye Laser Experimental Treatment 1 Intervention

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the pulsed dye laser arm will receive a series of six weekly to semi-weekly laser treatments treatments for up to 6 treatments with potential for reduced number of treatments if the hemangioma completely resolves. A 595-nm pulsed-dye laser (PDL, V-beam Perfecta, Candela Corp, Wayland, MA) with a dynamic cooling device (DCD) will be utilized for all treatments. This device is cleared by the FDA for clinical treatment of vascular lesions.

Group III: Observation Active Control 1 Intervention

After verification of eligibility criteria and obtaining informed consent of parent/guardian, infants randomized to the observation arm will be followed at study visits according to protocol.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

Findings from Research

In a study of 21 patients with superficial infantile hemangiomas, pulsed dye laser (PDL) treatment showed significantly better clinical improvement compared to topical timolol cream after an average of 3.39 treatment sessions over 2 months.

Both treatments were safe, with no patients experiencing permanent side effects, but the results suggest that PDL may be a more effective option for treating superficial proliferating hemangiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, open-label, rater-blinded and self-controlled pilot study of the treatment of proliferating superficial infantile hemangiomas with 0.5% topical timolol cream versus 595-nm pulsed dye laser. Ying, H., Zou, Y., Yu, W., et al.[2018]

Topical timolol maleate (5 mg/mL) is a safe and effective treatment for superficial infantile hemangiomas, showing significant improvement in hemoglobin levels after an average of 4 months of treatment.

For mixed hemangiomas, combined sequential dual-wavelength laser treatment (pulsed dye and Nd:YAG) was more effective than timolol, as it penetrated deeper to target blood vessels, resulting in greater improvement over an average treatment duration of 5.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical timolol solution versus laser in treatment of infantile hemangioma: a comparative study. Tawfik, AA., Alsharnoubi, J.[2015]

Topical beta-blocker timolol maleate 0.5% was effective in treating infantile hemangioma, showing a mean improvement of 47.0% based on physicians' assessments in a study of 102 patients.

When combined with pulsed dye laser treatment, the improvement increased to 66.5%, and importantly, no side effects were reported in either treatment group, highlighting the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical timolol maleate 0.5% for infantile hemangioma; it's effectiveness and/or adjunctive pulsed dye laser - single center experience of 102 cases in Korea. Park, KH., Jang, YH., Chung, HY., et al.[2018]

The combination of 595-nm pulsed-dye laser (PDL) and 0.5% timolol maleate solution is a safe and effective treatment for superficial infantile hemangioma (IH), with a high efficacy rate of 95.5% in patients treated early (≤2 months) compared to 86.1% in those treated later (>2 months).

Early intervention not only resulted in better treatment outcomes but also required fewer treatment sessions and was associated with a lower risk of permanent side effects, highlighting the importance of timely therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas. Shi, W., He, H., Jiang, J., et al.[2022]

References

1. India pubmed.ncbi.nlm.nih.gov

Pulsed dye laser and topical timolol gel versus pulse dye laser in treatment of infantile hemangioma: A double-blind randomized controlled trial. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Prospective, open-label, rater-blinded and self-controlled pilot study of the treatment of proliferating superficial infantile hemangiomas with 0.5% topical timolol cream versus 595-nm pulsed dye laser. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Topical timolol solution versus laser in treatment of infantile hemangioma: a comparative study. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Topical timolol maleate 0.5% for infantile hemangioma; it's effectiveness and/or adjunctive pulsed dye laser - single center experience of 102 cases in Korea. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A controlled study of topical 0.25% timolol maleate gel for the treatment of cutaneous infantile capillary hemangiomas. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Topical Timolol for Infantile Hemangiomas: Evidence for Efficacy and Degree of Systemic Absorption. [2017]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas. [2022]