Capillary MalformationsPhase 2NCT02883023
Electrosclerotherapy for Capillary Malformations
A Phase 2 study testing Electrosclerotherapy and Intralesional bleomycin injection in people with Capillary Malformations and Vascular Malformations, run by Sophie Horbach at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Capillary Malformations, Vascular Malformations
- What is being tested?
- Electrosclerotherapy and Intralesional bleomycin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2016to Mar 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Academic Medical Center (AMC)
Amsterdam, North Holland, 1105AZ
Sophie E Horbach, MD, 0031205666679, s.e.horbach@amc.uva.nl
Albert Wolkerstorfer, MD PhD, a.wolkerstorfer@amc.uva.nl
About this study
Official title: Electrosclerotherapy as a Novel Treatment Option for Capillary Malformations: A Pilot Study
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.
Read the 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
- Being tested
- Electrosclerotherapy, Intralesional bleomycin injection
- Keywords
- Bleomycin, Electroporation
- Medical subject headings
- Capillary Malformations, Congenital, 1, Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElectrosclerotherapyOther
Also called Electrochemotherapy
Combination of intralesional bleomycin sclerotherapy and electroporation
Intralesional bleomycin injectionDrug
Also called bleomycin sclerotherapy
Local intralesional injections with bleomycin
| Study group | Role | What they receive |
|---|---|---|
| Electrosclerotherapy | Experimental | One region of interest in the capillary malformation (approximately 1.5x1.5cm)will be treated with electrosclerotherapy Receives: Other: Electrosclerotherapy |
| Intralesional bleomycin injections | Active comparator | One region of interest in the capillary malformation will be treated with intralesional bleomycin injections without electroporation Receives: Drug: Intralesional bleomycin injection |
| No treatment | No intervention | One region of interest in the capillary malformation (approximately 1.5x1.5cm)will not be treated. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient and Observer global assessment of capillary malformation (POSAS instrument)
Change in patient and observer assessment of vascularity, pigmentation, thickness, pliability, relief, surface area and general opinion.
Measured: 7 weeks
Secondary outcomes (3)
Adverse events
Any adverse event or serious adverse event occurring after intervention
Measured: 7 weeks
Colorimetry
Change in color of capillary malformation in relation the contralateral healthy skin
Measured: 7 weeks
Optical imaging (laser speckle imaging)
Change in blood perfusion measured with non invasive imaging using light
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2016 (estimated)
- Study startNov 2016
- Primary completionJan 2018 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Capillary MalformationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sophie Horbach
- Sponsor type
- University, hospital or other
- Collaborators
- IGEA
- Responsible party
- Sponsor-investigator, Sophie Horbach, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Chantal M van der Horst, MD PhD, Principal investigator, Academic Medical Center (AMC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02883023
- Sponsor's protocol ID
- 58824
- Status last verified
- Jun 2017
- First submitted
- 22 Aug 2016
- Last updated
- 27 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31574025Horbach 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.
PubMed 29138199
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrosclerotherapy as a Novel Treatment Option for Capillary Malformations: A Pilot Study
- ClinicalTrials.gov ID
- NCT02883023
- Acronym / sponsor ID
- 58824
- Conditions
- Capillary Malformations, Vascular Malformations
- Keywords
- Bleomycin, Electroporation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sophie HorbachUniversity, hospital or other
- Collaborators
- IGEA
- Study start
- Nov 2016
- Primary completion
- Jan 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 30 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Electrosclerotherapy | Experimental | Other: ElectrosclerotherapyOne region of interest in the capillary malformation (approximately 1.5x1.5cm)will be treated with electrosclerotherapy |
| Intralesional bleomycin injections | Active comparator | Drug: Intralesional bleomycin injectionOne region of interest in the capillary malformation will be treated with intralesional bleomycin injections without electroporation |
| No treatment | No intervention | –One region of interest in the capillary malformation (approximately 1.5x1.5cm)will not be treated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElectrosclerotherapyAlso: ElectrochemotherapyCombination of intralesional bleomycin sclerotherapy and electroporation | Other | Electrosclerotherapy |
| Intralesional bleomycin injectionAlso: bleomycin sclerotherapyLocal intralesional injections with bleomycin | Drug | Intralesional bleomycin injections |
Primary outcome
Patient and Observer global assessment of capillary malformation (POSAS instrument)
Time frame: 7 weeks
Change in patient and observer assessment of vascularity, pigmentation, thickness, pliability, relief, surface area and general opinion.
3 secondary outcomes
Adverse events
Time frame: 7 weeks
Colorimetry
Time frame: 7 weeks
Optical imaging (laser speckle imaging)
Time frame: 7 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2017.
- Derived from this study: PubMed 31574025Horbach 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.
- Derived from this study: PubMed 29138199Horbach 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chantal M van der Horst, MD PhD principal investigator
Academic Medical Center (AMC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Electrosclerotherapy and Intralesional bleomycin injection in people with Capillary Malformations and Vascular Malformations, run by Sophie Horbach at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sophie E Horbach, MD (0031-20-5666679, s.e.horbach@amc.uva.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient and Observer global assessment of capillary malformation (POSAS instrument) (time frame: 7 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02883023, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2017.