Molluscum Contagiosum Skin Infection, Verruca Vulgaris
Conditions
Keywords
Plasma, Cryotherapy, Pediatrics, Warts, Molluscum, Dermatology, Cantharidin
Brief summary
This study is going to test a cold atmospheric plasma device (CAP), in particular a floating electrode-dielectric barrier device (FE-DBD), to treat warts and molluscum. The treatment device in this study generates cold atmospheric plasma (gaseous ionized molecules) to rid the virus from the body. Based on the successes of previous dermatologic studies, FE-DBD is being tested for this study to treat warts and molluscum. Patients will be enrolled to test the efficacy and safety of this device. The duration of the study is 4-12 weeks depending on treatment clearance. The number of lesions will be chosen by the dermatologist. Patients will receive standard of care therapy and/or NTAP depending on the number of lesions.
Interventions
The treatment device in this study generates cold atmospheric plasma. Cold atmospheric plasma has certain properties of plasma, such as ionized gas molecules. To create plasma, a pulse generator supplying 20 kilovolt pulse of 20-ns pulse width at 200 Hz (FPG10-01NM10, FID GmbH, Burbach, Germany) to a 5-mm diameter quartz-covered copper electrode of 10-cm length and 1 - 13mm quartz thickness. These nanosecond pulse parameters were chosen to provide sufficient treatment dose at the high level of plasma uniformity required to avoid any tissue damage. We will treat the lesions for approximately 1 to 2 minutes each, moving the electrode gently over the treatment area.
DEVICECryotherapy
Cryotherapy refers to the application of liquid nitrogen using a cryospray device in order to freeze a lesion of interest. Treatment is repeated every few weeks until the lesion of interest has disappeared. It is considered SOC for the treatment of warts.
DRUGCanthardin Collodion
Chemical compound that acts as a vesicant to form a blister around treatment area. The blister lifts the lesion of interest away from the skin, causing it to slough off in a few days. It is used as SOC for the treatment of Molluscum Contagiosum.
Sponsors
The Skin Center Dermatology Group
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
During a clinical care visit, if a patient is eligible and agrees to participate, lesions will be selected by the dermatologist prior to procedure.The lesions will be marked randomly for a certain treatment regimen. The number of lesions treated will not exceed standard of care (SOC) recommendations. They will be determined by provider assessment and anatomical location. Participants with one lesion will receive either non-thermal atmospheric plasma (NTAP) or SOC. SOC is cryotherapy for warts and cantharidin for molluscum. Participants with greater than 2 lesions will receive equal treatment of NTAP and SOC. The number of lesions treated will be based off the providers assessment and anatomical location. Treatment of a single lesion or an odd number of multiple lesions will be based off a randomized list. All SOC lesions will be treated first to reduce the number of patients not wanting return to the more painful modality.
Eligibility
Sex/Gender
ALL
Age
4 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* All patients from 4-21 years old with at least 1 lesion of either verruca vulgaris or molluscum contagiosum * Willingness of the participant and their guardian to provide consent when applicable
Exclusion criteria
* Unwillingness to participate in the study * Received any treatment on the lesion in the past month, as determined by review of participant medical record * Immunodeficiency as determined by review of participant medical record * Adverse response to prior treatments as determined by review of medical record * Signs of self-resolution as determined by study team members * Conditions that lead to excessive scarring as determined by study team members * Facial and genital lesions as determined by study team members
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numbers of Lesions With no Response | 12 weeks | Absence of change in appearance of targeted lesion. Molluscum is defined as the visualization of a central umbilication with polylobular, white to yellow, amorphous structures. A peripheral crown of radiating or punctiform vessels may also be present. Warts are defined as grouped papillae, with dotted or loop vessels, and/or hemorrhagic points and lines often surrounded by a whitish halo. |
| Numbers of Lesions With Partial Response | 12 weeks | There is change in the size, dyspigmentation, or discomfort of the targeted lesion as compared to its appearance and symptoms at the initial visit, but the lesion remains grossly visible. Molluscum is defined as the visualization of a central umbilication with polylobular, white to yellow, amorphous structures. A peripheral crown of radiating or punctiform vessels may also be present. Warts are defined as grouped papillae, with dotted or loop vessels, and/or hemorrhagic points and lines often surrounded by a whitish halo. Changes in the characteristics of the targeted lesions will be evaluated by a dermatologist and documented via photographs at follow-up visits at 4, 8, and 12 weeks, with the final outcome measured at the 12-week visit. |
| Numbers of Lesions With Complete Response | 12 weeks | Targeted lesion is no longer grossly visible. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-Treatment CAP Tolerability Questionnaire | 12 weeks | This questionnaire measures tolerability of cold atmospheric plasma treatment. Assessment of dryness, peeling, scaling, erythema, edema, stinging, burning sensation, itching, scarring and dyspigmentation will each be assessed individually. Participants were asked about these symptoms at a 1-week post-first treatment phone call, and then at every in-person follow up visit. Outcome data represents the number of total lesions in each treatment group in which a participant reported at least one of the above adverse symptoms. Results of specific AEs are detailed in the Adverse Event section. |
| Score of Visual Analogue Scale Associated With Treatment | 12 weeks | The visual analogue scale (VAS) is a validated subjective measurement of pain experienced by the patient. It consists of visual-numeric scale, numbered from 0-10. (0) indicate absence of pain or no pain at all, while (10) indicates severe pain or worst imaginable pain. This is supplemented by six faces with different expressions, ranging from happy to extremely upset. Each facial expression is assigned a numerical scale from 0 to 10. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cold Atmospheric Plasma (CAP) Only We conducted clinical trial of a floating electrode-dielectric barrier device (FE-DBD), a Cold Atmospheric Plasma (CAP) device for treatment of Verrucae Vulgaris and Molluscum Contagiosum. While novel to dermatology, publications exist regarding its use on human skin in adults and children. CAP devices utilize noble gases (such as helium) to deliver plasma state matter to the skin. The generated plasma stream is near skin temperature and exists on normal atmospheric pressure. In generation of plasma, there is no electric contact with the patient. Treatment does not increase skin surface temperature; the used helium gas is a noble gas and does not cause a chemical reaction with the skin. Flow of the gas is slow, thus there is no mechanical effect on skin.
Floating electrode-dielectric barrier device (FE-DBD) cold atmospheric plasma (CAP): The treatment device in this study generates CAP. CAP has certain properties of plasma, such as ionized gas molecules. To create plasma, a pulse generator, which supplied 17 kHz, 6 µs width pulse at a power density of approximately 2 W/cm2 (AAPlasma, Philadelphia, PA) was connected to a 10 mm diameter quartz-covered copper electrode of 50 mm length and 1 mm quartz thickness with one end fused. These nanosecond pulse parameters were chosen to provide sufficient treatment dose at the high level of plasma uniformity required to avoid any tissue damage. We treated lesions for 2 minutes each, moving the electrode gently over the treatment area. | 2 |
| Cold Atmospheric Plasma (CAP) Only We conducted clinical trial of a floating electrode-dielectric barrier device (FE-DBD), a Cold Atmospheric Plasma (CAP) device for treatment of Verrucae Vulgaris and Molluscum Contagiosum. While novel to dermatology, publications exist regarding its use on human skin in adults and children. CAP devices utilize noble gases (such as helium) to deliver plasma state matter to the skin. The generated plasma stream is near skin temperature and exists on normal atmospheric pressure. In generation of plasma, there is no electric contact with the patient. Treatment does not increase skin surface temperature; the used helium gas is a noble gas and does not cause a chemical reaction with the skin. Flow of the gas is slow, thus there is no mechanical effect on skin.
Floating electrode-dielectric barrier device (FE-DBD) cold atmospheric plasma (CAP): The treatment device in this study generates CAP. CAP has certain properties of plasma, such as ionized gas molecules. To create plasma, a pulse generator, which supplied 17 kHz, 6 µs width pulse at a power density of approximately 2 W/cm2 (AAPlasma, Philadelphia, PA) was connected to a 10 mm diameter quartz-covered copper electrode of 50 mm length and 1 mm quartz thickness with one end fused. These nanosecond pulse parameters were chosen to provide sufficient treatment dose at the high level of plasma uniformity required to avoid any tissue damage. We treated lesions for 2 minutes each, moving the electrode gently over the treatment area. | 2 |
| Cryotherapy Only Current standard of care (SOC) for treating Verruca Vulgaris in Children is cryotherapy. Patients randomized to this arm of the study have only one verruca lesion enrolled, and will receive SOC treatment for their identified condition.
Cryotherapy: Cryotherapy refers to the application of liquid nitrogen using a cryospray device in order to freeze a lesion of interest. Treatment is repeated every few weeks until the lesion of interest has disappeared. It is considered SOC for the treatment of warts. | 1 |
| Cryotherapy Only Current standard of care (SOC) for treating Verruca Vulgaris in Children is cryotherapy. Patients randomized to this arm of the study have only one verruca lesion enrolled, and will receive SOC treatment for their identified condition.
Cryotherapy: Cryotherapy refers to the application of liquid nitrogen using a cryospray device in order to freeze a lesion of interest. Treatment is repeated every few weeks until the lesion of interest has disappeared. It is considered SOC for the treatment of warts. | 1 |
| CAP and Cryotherapy Patients in this arm have more than one verruca lesion enrolled in the study. Thus, some of their lesions received CAP and some received SOC cryotherapy. | 11 |
| CAP and Cryotherapy Patients in this arm have more than one verruca lesion enrolled in the study. Thus, some of their lesions received CAP and some received SOC cryotherapy. | 109 |
| CAP and Cantharidin SOC for treatment of Molluscum Contagiosum is cantharidin. Patients randomized to this arm of the study will have multiple lesions, with some receiving cantharidin SOC treatment for their identified condition and some receiving cold atmospheric plasma (CAP).
Canthardin Collodion: Chemical compound that acts as a vesicant to form a blister around treatment area. The blister lifts the lesion of interest away from the skin, causing it to slough off in a few days. It is used as SOC for the treatment of Molluscum Contagiosum. | 3 |
| CAP and Cantharidin SOC for treatment of Molluscum Contagiosum is cantharidin. Patients randomized to this arm of the study will have multiple lesions, with some receiving cantharidin SOC treatment for their identified condition and some receiving cold atmospheric plasma (CAP).
Canthardin Collodion: Chemical compound that acts as a vesicant to form a blister around treatment area. The blister lifts the lesion of interest away from the skin, causing it to slough off in a few days. It is used as SOC for the treatment of Molluscum Contagiosum. | 37 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cryotherapy Only | CAP and Cryotherapy | CAP and Cantharidin | Cold Atmospheric Plasma (CAP) Only | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 11 Participants | 3 Participants | 2 Participants | 17 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10 years | 10 years | 7 years | 6.5 years | 9.1 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 10 Participants | 2 Participants | 2 Participants | 15 Participants |
| Region of Enrollment United States | 1 participants | 11 participants | 3 participants | 2 participants | 17 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 9 Participants | 1 Participants | 1 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 | 0 / 11 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 1 / 1 | 9 / 11 | 3 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 | 0 / 11 | 0 / 3 |
Outcome results
Primary
Numbers of Lesions With Complete Response
Targeted lesion is no longer grossly visible.
Time frame: 12 weeks
Population: The analyzed unit for this outcome is individual lesions. The sum of the number of participants in the two categories being higher than the total number of participants enrolled in the study is a result of the two categories not being mutually exclusive, as participants could have multiple lesions enrolled that were randomized to either CAP or SOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lesions Treated With Cold Atmospheric Plasma (CAP) | Numbers of Lesions With Complete Response | 40 lesions |
| Lesions Treated With Standard of Care (SOC) | Numbers of Lesions With Complete Response | 45 lesions |
Comparison: Outcome measures 1-3 were all tested together. Null hypothesis was that there was no difference in the degree of lesion resolution between the two treatment methods.p-value: 0.534Chi-squared
Primary
Numbers of Lesions With no Response
Absence of change in appearance of targeted lesion. Molluscum is defined as the visualization of a central umbilication with polylobular, white to yellow, amorphous structures. A peripheral crown of radiating or punctiform vessels may also be present. Warts are defined as grouped papillae, with dotted or loop vessels, and/or hemorrhagic points and lines often surrounded by a whitish halo.
Time frame: 12 weeks
Population: The analyzed unit for this outcome is individual lesions. The sum of the number of participants in the two categories being higher than the total number of participants enrolled in the study is a result of the two categories not being mutually exclusive, as participants could have multiple lesions enrolled that were randomized to either CAP or SOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lesions Treated With Cold Atmospheric Plasma (CAP) | Numbers of Lesions With no Response | 8 lesions |
| Lesions Treated With Standard of Care (SOC) | Numbers of Lesions With no Response | 9 lesions |
Comparison: Outcome measures 1-3 were all tested together. Null hypothesis was that there was no difference in the degree of lesion resolution between the two treatment methods.p-value: 0.534Chi-squared
Primary
Numbers of Lesions With Partial Response
There is change in the size, dyspigmentation, or discomfort of the targeted lesion as compared to its appearance and symptoms at the initial visit, but the lesion remains grossly visible. Molluscum is defined as the visualization of a central umbilication with polylobular, white to yellow, amorphous structures. A peripheral crown of radiating or punctiform vessels may also be present. Warts are defined as grouped papillae, with dotted or loop vessels, and/or hemorrhagic points and lines often surrounded by a whitish halo. Changes in the characteristics of the targeted lesions will be evaluated by a dermatologist and documented via photographs at follow-up visits at 4, 8, and 12 weeks, with the final outcome measured at the 12-week visit.
Time frame: 12 weeks
Population: The analyzed unit for this outcome is individual lesions. The sum of the number of participants in the two categories being higher than the total number of participants enrolled in the study is a result of the two categories not being mutually exclusive, as participants could have multiple lesions enrolled that were randomized to either CAP or SOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lesions Treated With Cold Atmospheric Plasma (CAP) | Numbers of Lesions With Partial Response | 23 lesions |
| Lesions Treated With Standard of Care (SOC) | Numbers of Lesions With Partial Response | 15 lesions |
Comparison: Outcome measures 1-3 were all tested together. Null hypothesis was that there was no difference in the degree of lesion resolution between the two treatment methods.p-value: 0.534Chi-squared
Secondary
Post-Treatment CAP Tolerability Questionnaire
This questionnaire measures tolerability of cold atmospheric plasma treatment. Assessment of dryness, peeling, scaling, erythema, edema, stinging, burning sensation, itching, scarring and dyspigmentation will each be assessed individually. Participants were asked about these symptoms at a 1-week post-first treatment phone call, and then at every in-person follow up visit. Outcome data represents the number of total lesions in each treatment group in which a participant reported at least one of the above adverse symptoms. Results of specific AEs are detailed in the Adverse Event section.
Time frame: 12 weeks
Population: The analyzed unit for this outcome is individual lesions. The sum of the number of participants in the two categories being higher than the total number of participants enrolled in the study is a result of the two categories not being mutually exclusive, as participants could have multiple lesions enrolled that were randomized to either CAP or SOC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lesions Treated With Cold Atmospheric Plasma (CAP) | Post-Treatment CAP Tolerability Questionnaire | 10 lesions |
| Lesions Treated With Standard of Care (SOC) | Post-Treatment CAP Tolerability Questionnaire | 42 lesions |
p-value: <0.001Chi-squared
Secondary
Score of Visual Analogue Scale Associated With Treatment
The visual analogue scale (VAS) is a validated subjective measurement of pain experienced by the patient. It consists of visual-numeric scale, numbered from 0-10. (0) indicate absence of pain or no pain at all, while (10) indicates severe pain or worst imaginable pain. This is supplemented by six faces with different expressions, ranging from happy to extremely upset. Each facial expression is assigned a numerical scale from 0 to 10.
Time frame: 12 weeks
Population: The analyzed unit for this outcome is individual lesions. The sum of the number of participants in the two categories being higher than the total number of participants enrolled in the study is a result of the two categories not being mutually exclusive, as participants could have multiple lesions enrolled that were randomized to either CAP or SOC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lesions Treated With Cold Atmospheric Plasma (CAP) | Score of Visual Analogue Scale Associated With Treatment | 2.5 units from 0-10 on VAS scale |
| Lesions Treated With Standard of Care (SOC) | Score of Visual Analogue Scale Associated With Treatment | 0.9 units from 0-10 on VAS scale |
Comparison: Null hypothesis: there was no difference in median pain levels between SOC and NTAP treated lesions.p-value: 0.142Wilcoxon Signed Rank Test