Electrosclerotherapy for Capillary Malformations

Sophie Horbach

Status and phase: Unknown; Phase 2

Conditions: Capillary Malformations; Vascular Malformations

Treatments: Drug: Intralesional bleomycin injection; Other: Electrosclerotherapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02883023

58824

Details and patient eligibility

About

Capillary malformations (port-wine stains) consist of abnormally developed capillary blood vessels in the skin. To date, laser therapy is the only widely accepted treatment modality for capillary malformations, but this therapy has a suboptimal effect in approximately 50-60% of patients.

Intralesional bleomycin injections (sclerotherapy) are a common effective treatment option for vascular malformations with blood vessels with larger diameters. However, bleomycin cannot be injected adequately in the small sized vessels of capillary malformations. The use of an electric field over the tissue (electroporation) may solve this problem: it increases cell membrane permeability and therefore promotes localized delivery of drugs, within (endothelial) cells.

Electroporation in combination with bleomycin sclerotherapy ('electrosclerotherapy') may therefore offer new therapeutic options for capillary malformations. This proof of principle study aims to explore the effectiveness, safety and feasibility of this potential treatment option in a within-patient-controlled pilot study.

Full description

Capillary malformations are congenital abnormalities of the capillaries in the skin. These abnormally developed blood vessels cause a red color of the skin (also known as 'port-wine stain'),often in combination with a cobble-stone like aspect of the skin. Currently, the only widely accepted treatment option is laser therapy, in which the abnormal blood vessels are targeted with photocoagulation. However, in approximately 50-60% of patients, treatment outcome of laser therapy is suboptimal. Furthermore, re-darkening of the capillary malformation often occurs after laser therapy. Hence, there is a need for an alternative treatment option - especially for treatment-resistant and recurrent capillary malformations.

Intralesional bleomycin injections (sclerotherapy) are a common treatment option for vascular malformations of blood vessels and lymphatic vessels with a larger diameter (venous and lymphatic malformations). According to the literature, this treatment is effective in approximately 80-90% of patients. Unfortunately, the diameter of capillary blood vessels is too small, and therefore adequate localized injections of bleomycin are not possible in capillary malformations.

'Electroporation' is a physical phenomenon that causes an alteration of the structure of cell membranes through the exposure of cells to a short but intense electric field; this modification of the cell membrane increases its permeability. After electroporation, molecules that normally do not cross the cell membrane, either by diffusion or by active transport, can reach the intracellular environment. Therefore, electroporation is an ideal method for localized drug delivery, in particular for localized bleomycin delivery.

The combination of electroporation and bleomycin is already used in a variety of skin lesions, such as squamous cell carcinoma, with a surprisingly high rate of complete remission. Especially in vascular tumors, such as Kaposi sarcoma, there is an extremely high percentage of complete remission (90%), since the combination of bleomycin and electroporation causes a 'vascular lock' and intravascular thrombosis of tumor vascularization, leading to tumor regression.

This phenomenon (intravascular thrombosis and lesion regression) is exactly the intended effect of capillary malformation treatment.

The investigators therefore hypothesize that intralesional bleomycin injections combined with electroporation (electrosclerotherapy) can be an alternative treatment option for capillary malformations. This proof of principle study aims to explore the feasibility of this potential treatment option in a small patient sample.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with ≥1 completely or partially hypertrophic capillary malformation not exclusively located in the skin of the face, the skin overlying joints or in mucosal tissue
• Age ≥ 18 years
• Fitzpatrick skin type 1-3 without evident sun tan

Exclusion criteria

• Pregnant or breastfeeding women
• Women with childbearing potential not using contraception
• Patients with chronic renal dysfunction of GFR <50 ml/minute
• Patients with chronic pulmonary dysfunction, active pulmonary infections or previous bleomycin lung toxicity
• Patients with ataxia teleangiectasia
• Patients with previous allergic reactions to bleomycin
• Patients who already received the maximum dose of bleomycin (400 mg or 400000 IU/m2)
• Patients with implanted electrical devices such as pacemakers or ICD's
• Patients with clinically manifested arrhythmia
• Patients with epilepsy
• Patients who are not able to return to the hospital for follow-up visits
• Patients who are likely not able to understand the terms and risks of the study (e.g. cognitive impairment)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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20 participants in 3 patient groups

Electrosclerotherapy

Experimental group

Description:

One region of interest in the capillary malformation (approximately 1.5x1.5cm)will be treated with electrosclerotherapy

Treatment:

Other: Electrosclerotherapy

Intralesional bleomycin injections

Active Comparator group

Description:

One region of interest in the capillary malformation will be treated with intralesional bleomycin injections without electroporation

Treatment:

Drug: Intralesional bleomycin injection

No treatment

No Intervention group

Description:

One region of interest in the capillary malformation (approximately 1.5x1.5cm)will not be treated.