madman
Super Moderator
Safety and effectiveness of nano-pulse stimulation™ technology to treat acne vulgaris of the back (2023)
Bruce E. Katz MD | Mark S. Nestor MD, Ph.D. | Richard Nuccitelli Ph.D. | Lauren Jauregui Johnston BS | William A. Knape BS
Abstract
Background and Objectives: This feasibility study describes the effects of Nanopulse stimulation™ (NPS™) technology using the CellFX™ System on acne vulgaris of the back with the objectives of demonstrating safety and effectiveness. The CellFX System applies nanosecond pulses of electrical energy to induce highly localized regulated cell death (RCD) in the cellular structures of the targeted zone with no thermal effect on the tissue and negligible effects on surrounding non-cellular components.
Study Design/Materials and Methods: Seventeen subjects were enrolled at two sites with thirteen subjects completing treatment. Three 7 X 7 cm regions containing at least five bacne lesions each were identified, one region treated with the CellFX across three treatment sessions, the second region treated as a sham using microneedle tip placement without delivering energy, and the third as an untreated control.
Results: CellFX-treated areas showed an average reduction of acne lesions of 82% by 90 days post-last procedure. Acne improvement was observed in 100% of CellFXtreated regions compared to 39% improvement in Sham regions and 31% improvement in the control regions. The most common skin effects were erythema and hyperpigmentation observed in 23% and 92% of the subjects, respectively, at the last time point. No serious adverse events were reported.
Conclusions: CellFX is a safe and effective procedure for clearing back acne.
1 | INTRODUCTION
Acne vulgaris is a common skin condition typically associated with excess production of sebum by oil-producing glands and often involving the bacterium, Cutibacterium acnes (formerly Propionibacterium acnes). It commonly occurs on the face, chest, shoulders, and upper back and affects 35% to nearly 100% of teenagers and young adults, depending on the country and specific age group.1,2 Given the virtually ubiquitous nature of acne in teenagers, there remains an appreciable need for novel therapies. Some new approaches include oxybrasion,3 microdermabrasion with Pyruvic acid,4 and cosmetic acids.5
The relatively new non-thermal energy modality, Nano-pulse stimulation™ Therapy (NPS™), has been found to target both the sebum secretory glands and the Cutibacterium acnes bacterium by inducing regulated cell death6,7 in dermal secretory glands8,9 and killing C. acnes in the biofilm condition normally found on the skin.10 Therefore, it may become a very effective treatment for acne. Here we report on the first clinical trial investigating the use of CellFX™ to treat back acne on thirteen subjects. Previous studies using the CellFX to treat skin lesions demonstrated efficacy in clearing seborrheic keratosis,11 sebaceous hyperplasia,8, and non-genital warts.12
Much is known about the mechanism by which NPS initiates regulated cell death (RCD) in benign skin lesions.6 The main targets of NPS are the lipid bilayer membranes surrounding cells and intracellular organelles. The electrical pulses are strong enough to force water molecules into those membranes to form thousands of small, transient nanopores with each pulse, allowing small molecules, such as ions and water, to cross the membrane barriers. When a sufficient number of these nanopulses are applied to the target area, the cells are stressed by the subsequent increase in intracellular calcium13 as well as the disruption of ATP production due to the loss of the mitochondrial membrane potential14,15 which then initiates a process common to all cells, often called regulated cell death, including apoptosis. There is abundant evidence indicating that CellFX treatments initiate several steps in the RCD pathway including DNA fragmentation,16 reactive oxygen species generation,17,18 calreticulin externalization,19 and mitochondria swelling.15 This leads to a slow cell death which allows the recruitment of dendritic cells to phagocytize the dead cells and initiate an immune response if any foreign antigens are present.19–21
4 | DISCUSSION
This is the first study of tissue lesion effects of CellFX treatment on back acne and the results indicate an impressive effectiveness of CellFX at eliminating acne lesions. A complete clearance of all acne lesions was observed in 31% of subjects at both the highest and lowest energy levels with an average efficacy of an 82% reduction at 90 days post-treatment across all energy levels evaluated. This compares to a 67% and 62% reduction in sham and control regions, respectively. This large short-term reduction in the number of acne lesions in these control regions was unexpected and suggests that the CellFX treatment on neighboring skin may somehow reflect a potential loco-regional effect extending beyond the CellFX-treated areas to influence the lesions in untreated regions as well (Figure 7). Areas treated with CellFX showed a fast response and sustained reduction of acne lesions through 90 days post-last treatment, with an average of 80% decrease in acne lesions seen by 30 days post-treatment. When equated to the response levels of the CellFX group, 48% and 43% reductions in acne lesions were seen in the sham and control groups by 30 days, respectively. While no histology of the treated lesions was collected in this study, two previous studies8,9 included histological sections of NPS-treated skin that indicated the clearance of sebaceous glands within the treatment zone.
High sebum levels have often been associated with acne in teenagers and sebum levels did decline over the first 30 days following CellFX treatment. However, there was no significant relationship found between the sebum levels and the change in lesion count.
The overall skin quality was also evaluated by the physician for each study area at 30-, 60-, and 90-days post-last CellFX procedure. For skin treated with CellFX, the skin quality was rated better for more than 50% of the cases compared to only 8% of the sham-treated area (Table 2). This is an added benefit of CellFX treatment because it not only reduces the lesion count but also improves the overall skin quality. Hyperpigmentation was present in most subjects but continued to improve over time and was expected to resolve based on our observations of a similar treatment of sebaceous hyperplasia8 that was carried out for a full year.
4.1 | Limitations
The main limitation of the CellFX procedure is the requirement for the lidocaine injection prior to each treatment to reduce pain. A secondary limitation is a hyperpigmentation that occurs in Fitzpatrick IV patients.
5 | CONCLUSION
In summary, it is concluded that the CellFX Procedure is a safe and effective treatment for back acne and can achieve a short-term improvement in the number of acne lesions on the back. We followed 90 days post-last treatment with no increase in lesions. Some patients returned after 6 months with the maintenance of clearance. Further studies will be needed to further assess the longevity of the results as well as the effectiveness of acne in other regions of the body.
Bruce E. Katz MD | Mark S. Nestor MD, Ph.D. | Richard Nuccitelli Ph.D. | Lauren Jauregui Johnston BS | William A. Knape BS
Abstract
Background and Objectives: This feasibility study describes the effects of Nanopulse stimulation™ (NPS™) technology using the CellFX™ System on acne vulgaris of the back with the objectives of demonstrating safety and effectiveness. The CellFX System applies nanosecond pulses of electrical energy to induce highly localized regulated cell death (RCD) in the cellular structures of the targeted zone with no thermal effect on the tissue and negligible effects on surrounding non-cellular components.
Study Design/Materials and Methods: Seventeen subjects were enrolled at two sites with thirteen subjects completing treatment. Three 7 X 7 cm regions containing at least five bacne lesions each were identified, one region treated with the CellFX across three treatment sessions, the second region treated as a sham using microneedle tip placement without delivering energy, and the third as an untreated control.
Results: CellFX-treated areas showed an average reduction of acne lesions of 82% by 90 days post-last procedure. Acne improvement was observed in 100% of CellFXtreated regions compared to 39% improvement in Sham regions and 31% improvement in the control regions. The most common skin effects were erythema and hyperpigmentation observed in 23% and 92% of the subjects, respectively, at the last time point. No serious adverse events were reported.
Conclusions: CellFX is a safe and effective procedure for clearing back acne.
1 | INTRODUCTION
Acne vulgaris is a common skin condition typically associated with excess production of sebum by oil-producing glands and often involving the bacterium, Cutibacterium acnes (formerly Propionibacterium acnes). It commonly occurs on the face, chest, shoulders, and upper back and affects 35% to nearly 100% of teenagers and young adults, depending on the country and specific age group.1,2 Given the virtually ubiquitous nature of acne in teenagers, there remains an appreciable need for novel therapies. Some new approaches include oxybrasion,3 microdermabrasion with Pyruvic acid,4 and cosmetic acids.5
The relatively new non-thermal energy modality, Nano-pulse stimulation™ Therapy (NPS™), has been found to target both the sebum secretory glands and the Cutibacterium acnes bacterium by inducing regulated cell death6,7 in dermal secretory glands8,9 and killing C. acnes in the biofilm condition normally found on the skin.10 Therefore, it may become a very effective treatment for acne. Here we report on the first clinical trial investigating the use of CellFX™ to treat back acne on thirteen subjects. Previous studies using the CellFX to treat skin lesions demonstrated efficacy in clearing seborrheic keratosis,11 sebaceous hyperplasia,8, and non-genital warts.12
Much is known about the mechanism by which NPS initiates regulated cell death (RCD) in benign skin lesions.6 The main targets of NPS are the lipid bilayer membranes surrounding cells and intracellular organelles. The electrical pulses are strong enough to force water molecules into those membranes to form thousands of small, transient nanopores with each pulse, allowing small molecules, such as ions and water, to cross the membrane barriers. When a sufficient number of these nanopulses are applied to the target area, the cells are stressed by the subsequent increase in intracellular calcium13 as well as the disruption of ATP production due to the loss of the mitochondrial membrane potential14,15 which then initiates a process common to all cells, often called regulated cell death, including apoptosis. There is abundant evidence indicating that CellFX treatments initiate several steps in the RCD pathway including DNA fragmentation,16 reactive oxygen species generation,17,18 calreticulin externalization,19 and mitochondria swelling.15 This leads to a slow cell death which allows the recruitment of dendritic cells to phagocytize the dead cells and initiate an immune response if any foreign antigens are present.19–21
4 | DISCUSSION
This is the first study of tissue lesion effects of CellFX treatment on back acne and the results indicate an impressive effectiveness of CellFX at eliminating acne lesions. A complete clearance of all acne lesions was observed in 31% of subjects at both the highest and lowest energy levels with an average efficacy of an 82% reduction at 90 days post-treatment across all energy levels evaluated. This compares to a 67% and 62% reduction in sham and control regions, respectively. This large short-term reduction in the number of acne lesions in these control regions was unexpected and suggests that the CellFX treatment on neighboring skin may somehow reflect a potential loco-regional effect extending beyond the CellFX-treated areas to influence the lesions in untreated regions as well (Figure 7). Areas treated with CellFX showed a fast response and sustained reduction of acne lesions through 90 days post-last treatment, with an average of 80% decrease in acne lesions seen by 30 days post-treatment. When equated to the response levels of the CellFX group, 48% and 43% reductions in acne lesions were seen in the sham and control groups by 30 days, respectively. While no histology of the treated lesions was collected in this study, two previous studies8,9 included histological sections of NPS-treated skin that indicated the clearance of sebaceous glands within the treatment zone.
High sebum levels have often been associated with acne in teenagers and sebum levels did decline over the first 30 days following CellFX treatment. However, there was no significant relationship found between the sebum levels and the change in lesion count.
The overall skin quality was also evaluated by the physician for each study area at 30-, 60-, and 90-days post-last CellFX procedure. For skin treated with CellFX, the skin quality was rated better for more than 50% of the cases compared to only 8% of the sham-treated area (Table 2). This is an added benefit of CellFX treatment because it not only reduces the lesion count but also improves the overall skin quality. Hyperpigmentation was present in most subjects but continued to improve over time and was expected to resolve based on our observations of a similar treatment of sebaceous hyperplasia8 that was carried out for a full year.
4.1 | Limitations
The main limitation of the CellFX procedure is the requirement for the lidocaine injection prior to each treatment to reduce pain. A secondary limitation is a hyperpigmentation that occurs in Fitzpatrick IV patients.
5 | CONCLUSION
In summary, it is concluded that the CellFX Procedure is a safe and effective treatment for back acne and can achieve a short-term improvement in the number of acne lesions on the back. We followed 90 days post-last treatment with no increase in lesions. Some patients returned after 6 months with the maintenance of clearance. Further studies will be needed to further assess the longevity of the results as well as the effectiveness of acne in other regions of the body.
