Electrosclerotherapy for Capillary Malformations

NCT ID: NCT02883023

Last Updated: 2017-06-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-03-31

Brief Summary

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.

Detailed 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.

Conditions

Capillary Malformations; Vascular Malformations

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Electrosclerotherapy

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

Group Type: EXPERIMENTAL

Electrosclerotherapy

Intervention Type: OTHER

Combination of intralesional bleomycin sclerotherapy and electroporation

Intralesional bleomycin injections

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

Group Type: ACTIVE_COMPARATOR

Intralesional bleomycin injection

Intervention Type: DRUG

Local intralesional injections with bleomycin

No treatment

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Electrosclerotherapy

Combination of intralesional bleomycin sclerotherapy and electroporation

Intervention Type: OTHER

Intralesional bleomycin injection

Local intralesional injections with bleomycin

Intervention Type: DRUG

Other Intervention Names

Electrochemotherapy; bleomycin sclerotherapy

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IGEA

INDUSTRY

Sponsor Role: collaborator

Sophie Horbach

OTHER

Sponsor Role: lead

Responsible Party

Sophie Horbach

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Chantal M van der Horst, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Center (AMC)

Locations

Academic Medical Center (AMC)

Amsterdam, North Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Sophie E Horbach, MD

Role: CONTACT

s.e.horbach@amc.uva.nl

0031-20-5666679

Facility Contacts

Sophie E Horbach, MD

Role: primary

s.e.horbach@amc.uva.nl

0031205666679

Albert Wolkerstorfer, MD PhD

Role: backup

a.wolkerstorfer@amc.uva.nl

References

Horbach SER, Wolkerstorfer A, Jolink F, Bloemen PR, van der Horst CMAM. Electrosclerotherapy as a Novel Treatment Option for Hypertrophic Capillary Malformations: A Randomized Controlled Pilot Trial. Dermatol Surg. 2020 Apr;46(4):491-498. doi: 10.1097/DSS.0000000000002191.

Reference Type: DERIVED

PMID: 31574025 (View on PubMed)

Horbach SER, Wolkerstorfer A, de Bruin DM, Jansen SM, van der Horst CMAM. Electrosclerotherapy for capillary malformations: study protocol for a randomised within-patient controlled pilot trial. BMJ Open. 2017 Nov 14;7(11):e016401. doi: 10.1136/bmjopen-2017-016401.

Reference Type: DERIVED

PMID: 29138199 (View on PubMed)

Other Identifiers

58824

Identifier Type: -

Identifier Source: org_study_id