FLE线粒体面部年轻化试验文献
FLE线粒体面部年轻化试验文献
FLE线粒体面部年轻化试验文献
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Clinical, Cosmetic and Investigational Dermatology Dovepress
open access to scienti[[f]]ic and medical research
open access Full Text article ClInIC al TrIal repor T
a randomized, placebo-controlled, single-blinded,
split-[[f]]aced clinical trial evaluating the efficacy and
sa[[f]]ety of KloX-001 gel formulation with KloX
light-emitting diode light on [[f]]acial rejuvenation
andreas nikolis1 Purpose: Many treatment modalities exist to counteract the e[[f]]fects of cutaneous aging. Ablative
Steven Bernstein2 methods have been the mainstay [[f]]or nonsurgical facial rejuvenation. In recent years, nonablative
Brian Kinney3 techniques have been developed with the aim o[[f]] achieving facial rejuvenation without epidermal
nicolo Scuderi4 damage. Light-emitting diode (LED) photorejuvenation is a novel nonablative technique that
induces collagen synthesis through biophotomodulatory pathways.
Shipra rastogi5
Materials and methods: A single-center, randomized, single-blinded, placebo-controlled,
John S Sampalis6
split-[[f]]aced clinical trial was designed. Thirty-two patients were enrolled for a 12-week study.
Section, Westmount, QC, Canada;
[[f]]ormulation and white LED (placebo) light; Group B, treatment with a placebo/base gel (no
o[[f]] Montreal Health Centre, Montreal, active chromophore) formulation and KLOX LED light; Group C, treatment with KLOX-001
QC, Canada; 3Department o[[f]] plastic
gel [[f]]ormulation and KLOX LED light; and Group D, treatment with the standard skin reju-
Surgery, USC School o[[f]] Medicine,
Beverley Hills, Ca, USa; 4Department venating treatment (0.1% retinol-based cream). Patients received treatment at weeks 0, 1, 2,
o[[f]] plastic and reconstructive Surgery, and 3, and returned to the clinic at weeks 4, 8, and 12 for clinical assessments performed by
la Sapienza, rome, Italy; 5KloX
an independent, blinded committee o[[f]] physicians using subjective clinician assessment scales.
Technologies, laval, 6JSS Medical
research, Montreal, QC, Canada Tolerability, adverse outcomes, and patient satis[[f]]action were also assessed.
Results: Analysis demonstrated that the KLOX LED light with KLOX placebo/base gel and
the KLOX LED light + KLOX-001 gel [[f]]ormulation groups were superior to standard of care
and KLOX-001 gel [[f]]ormulation with placebo light on subjective clinical assessment and mul-
tiple wrinkle scales, with statistically signi[[f]]icant results obtained for brow positioning, perioral
wrinkling, and total wrinkle score.
Conclusion: The study results show that KLOX LED light with KLOX-001 gel [[f]]ormulation and
KLOX LED light with KLOX placebo/base gel are e[[f]]fective, safe, well-tolerated, and painless
treatment modalities [[f]]or skin rejuvenation.
Keywords: biophotonics, skin rejuvenation, chromophore, rejuvenation, non-invasive
Introduction
Cutaneous aging is a natural inevitable process leading to a considerable desire [[f]]or
many patients to achieve a more youth[[f]]ul look. Many treatment modalities exist, both
Correspondence: andreas nikolis medical and nonmedical, to improve an individual’s physical appearance as well as their
Victoria park, plastic Surgery Section,
perception o[[f]] their appearance, consequently influencing psychological well-being.1
Quebec, H3Z1C3 Canada Cutaneous aging results [[f]]rom a combination of intrinsic biological factors and extrinsic
Tel +1 514 488 7722 environmental [[f]]actors2 leading to a variety of clinical manifestations, including fine
Fax +1 514 488 3830
email anikolis@vicpark.com lines and rhytides, dyspigmentation, telangiectasia, elastosis, and textural irregularities.3
submit your manuscript | www.dovepress.com Clinical, Cosmetic and Investigational Dermatology 2016:9 115–125 115
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php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work
http://dx.doi.org/10.2147/CCID.S100697 you hereby accept the Terms. Non-commercial uses o[[f]] the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission [[f]]or commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
nikolis et al Dovepress
Histologically, aged skin presents with epidermal thickening, Drug Administration and the American National Standard
diminished collagen synthesis leading to dermal atrophy Institute Z135 regulations on optical exposure to skin. As
and loss o[[f]] dermal papillae, as well as a fragmented and the blue light illuminates the chromophores, it gets converted
disorganized elastin network.3–8 Extrinsic [[f]]actors are many into a broad range of wavelengths.
and include tobacco use, sleeping positions, repetitive [[f]]acial This study was designed to assess the efficacy, tolerability,
expressions, and ultraviolet radiation [[f]]rom the sun.1,3 Current and safety of KLOX-001 gel formulation with KLOX LED
nonsurgical therapies are centered on ablative methods o[[f]] light on skin rejuvenation in women. The primary endpoint
skin rejuvenation. These include chemical peels, dermabra- was subjective clinical assessment o[[f]] KLOX-001 gel formu-
sion, and laser resur[[f]]acing.9–13 Ablative methods remove the lation and KLOX LED light, alone or in combination, on
epidermis and induce a controlled [[f]]orm of wounding, thus skin rejuvenation of the face after four weekly treatments.
promoting collagen synthesis and dermal extracellular matrix Secondary endpoints included the e[[f]]fects of treatment with
remodeling.13–15 These procedures may require complex KLOX-001 gel [[f]]ormulation and KLOX LED light on the
postoperative care, can be quite pain[[f]]ul, and can also lead severity of glabellar lines, marionette lines and perioral
to signi[[f]]icant complications.9,16,17 wrinkling, nasolabial wrinkle severity, forehead wrinkling,
The development o[[f]] nonablative techniques stems from periocular wrinkling and crow’s feet, cheek wrinkling, overall
patients’ desire to decrease discom[[f]]ort and downtime and photo-damage, subjective patient satisfaction with treatment,
clinicians’ desire to o[[f]]fer simpler, effective alternatives with pain, and erythema, histologic changes, as well as patient
[[f]]ewer side effects.13,18–21 Nonablative skin rejuvenation can safety and tolerability.
be classi[[f]]ied into two types: type I photorejuvenation targets
primarily telangiectasia and irregular pigmentation, whereas Materials and methods
type II photorejuvenation aims [[f]]or wrinkle and fine line A single-center, randomized, single-blinded, placebo-
reduction and skin tightening.13,22 controlled, split-control-[[f]]aced clinical trial was designed. The
Light-emitting diode (LED) photorejuvenation is a novel KLOX internal clinical number [[f]]or this study is CL-K1001-
noninvasive procedure that is nonthermal, atraumatic, and 001. The duration o[[f]] active phase of the study was 12 weeks.
induces collagen synthesis through biophotomodulatory Ethics approval was obtained [[f]]rom the Canadian SHIELD
pathways.9 Subtypes o[[f]] LED photomodulation include, but Ethics Review Board, which reviewed the study protocol and
are not limited to, the photodynamic and the biophotonic [[f]]ound it to be acceptable. Written consent was also obtained
plat[[f]]orms. The biophotonic platform is distinct from the from the patients by KLOX Technologies for the use of the
photodynamic one in that both use a combination o[[f]] LED photos in this paper.
light and a chromophore-rich gel; however, in the biophotonic All eligible patients (Table 1) who agreed to participate
plat[[f]]orm, chromophores act topically to enhance the effects in the study and signed an informed consent form were
o[[f]] the LED light and are neither absorbed nor metabolized. randomized in a 1:1:1:1 ratio into one of the following four
Many clinical trials have shown the e[[f]]ficacy of LED therapy groups: Group A received treatment for half the face with
in skin rejuvenation.9,20,23–29 They include increased collagen KLOX-001 gel [[f]]ormulation and white LED (placebo) light
deposition and decreased collagen degradation by upregula- and the contralateral side was treated with a placebo (base
tion o[[f]] fibroblast activity.9,19 gel – no chromophores) formulation and light; Group B
Preliminary studies with the KLOX-001 [[f]]ormulation received treatment for half the face with a placebo/base gel
demonstrate in vitro antibacterial e[[f]]ficacy and a stimulatory formulation and KLOX LED light and the contralateral side
e[[f]]fect on human dermal fibroblasts. Additionally, KLOX-001 was treated as Group A; Group C received treatment for half
gel [[f]]ormulation and KLOX LED light biophotonic combi- the face with KLOX-001 gel formulation and KLOX LED
nation has been shown to decrease necrosis in the rat [[f]]lap light and the contralateral side was treated as the other con-
model, as well as increase collagen [[f]]ibrin deposition.30 The trols; and Group D received treatment for half the face with
KLOX-001 topical gel [[f]]ormulation comprises principally of the standard skin rejuvenating treatment (0.1% retinol-based
an oxidant, chromophores, and a hydrophilic gel carrier. The cream) and the control side received a basic moisturizer. A[[f]]ter
KLOX LED light delivers symmetrical peak wavelengths in initial randomization, patients were randomly allocated in a
the visible range (400–470 nm) with a peak at 446 nm. It 1:1 ratio to treatment o[[f]] either right or left side.
produces a power density o[[f]] 150 mW/cm2 at a distance of Prior to treatment, all patients received a single micro-
Dovepress
Dovepress KloX-001 gel [[f]]ormulation with KloX leD light in facial rejuvenation
Table 1 Study inclusion and exclusion criteria was completed and a standardized clinical assessment
Inclusion criteria was per[[f]]ormed. Patients were asked to complete a short
[[f]]ollowing each visit.
The primary endpoint o[[f]] the study was the change in the
Exclusion criteria
committee o[[f]] three physicians using a subjective 5-point
scale [[f]]rom 0 to 4 (0 = worse; 1 = little or no improvement
[76%–100%]). In addition, the committee o[[f]] physicians
assessed: 1) severity o[[f]] glabellar lines using the 4-point
completing the study
system32 (perioral wrinkling was also assessed using the
using the modi[[f]]ied Fitzpatrick Wrinkle Scale;35 4) forehead
wrinkling using the 5-point photonumeric Forehead Lines
kling using Lemperle’s 6-point Wrinkle Assessment Scale,
Day’s Wrinkle Severity Rating Scale, and Fitzpatrick’s
wrinkle scoring system;32,38,39 7) overall photo-damage
using Glogau’s classi[[f]]ication of patient photoaging types
were taken [[f]]rom the retroauricular region at weeks 0 and subjective satisfaction with treatment, as measured by the
while minimizing con[[f]]ounding factors. During the active of board-certified physicians who were trained in scoring
treatment period, there were a total o[[f]] four weekly visits. using standardized patient photographs. They were not
Patients received treatment on one hal[[f]] of the face and the blinded to time elapsed from treatment, but were blinded to
biopsy region. Groups A and C were treated with a 2 mm treatment type and side.
thick layer o[[f]] KLOX-001 gel formulation on the experimental Thirty-two patients were enrolled. Sample size was
side and a nonchromophore placebo/base gel [[f]]ormulation on calculated on the basis of detecting a 20% difference in pri-
the control side. Groups B and C were treated with KLOX mary outcome measure with a power o[[f]] 80%. The secondary
LED light by the light source at a distance o[[f]] 5 cm from the outcome measure was the change in the total wrinkle score
skin sur[[f]]ace (power density of 150 mW/cm2) for a duration (TWS) from baseline to 4, 8, and 12 weeks. The TWS was
o[[f]] 5 minutes per facial subunit to ensure complete facial calculated as the sum of patient’s self-assessment of the
coverage on the experimental side and with sham placebo horizontal, marionette, glabellar, and crow’s [[f]]eet wrinkle
light (white LED) on the control side. Group D received a severity classi[[f]]ied as 1 = none, 2 = mild, 3 = moderate, and 5
standard skin rejuvenating treatment (0.1% retinol-based = severe. The TWS had a minimum value o[[f]] 4 and maximum
cream) on the experimental side and a basic moisturizer on value o[[f]] 20, with higher values indicating higher severity.
the control side. Tolerability o[[f]] treatment was assessed using the 4-point
During treatment, all patients were blinded with external Pain Assessment Scale (1 = no pain; 2 = some pain; 3 = very
eyelid protectors to shield the retina [[f]]rom direct illumina- painful, but bearable; and 4 = unbearable pain). Descriptive
tion. Only the treatment segment o[[f]] the face was exposed statistics (including mean, standard deviation, median, range,
to light. A subjective patient assessment questionnaire and 95% con[[f]]idence intervals) were produced for continuous
Clinical, Cosmetic and Investigational Dermatology 2016:9 submit your manuscript | www.dovepress.com 117
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| nikolis et al | Dovepress | ||||
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| scale variables and [[f]]requency distributions for categorical | Results |
scale variables. Thirty-two patients satis[[f]]ied the inclusion/exclusion criteria.
The chi-square statistic was used to assess the between-
Only two (6.2%) subjects discontinued the study prior to
group di[[f]]ferences with respect to the primary outcome
completion; they were only lost to [[f]]ollow-up at week 12
| measure. For the secondary outcome measures, the statisti- | (Table 2). |
cal analysis involved the use o[[f]] multivariate general linear Analysis of subjective physician assessment demon strated
models, adjusting [[f]]or patient’s age and baseline values of that the group treated with KLOX LED light + KLOX-001
the TWS. The general linear models were used to produce
gel [[f]]ormulation had superior performance when compared
estimates o[[f]] placebo-adjusted least-square mean estimates
to the other treatment groups, with statistically signi[[f]]icant
[[f]]or the change in TWS at each visit. This was done by esti- results seen for changes in brow positioning (P=0.001) and
mating the placebo-adjusted estimate o[[f]] the TWS at each perioral wrinkling (P=0.018) (Table 3, Figures 1–4).
visit [[f]]or each patient using a predictive linear regression Analysis of TWS least-square mean adjusted predicted
model to o[[f]]fset the TWS of each KLOX-treated patient by
value changes demonstrated that while the KLOX LED light
the estimated standard o[[f]] care (SOC) value. When com-
with base KLOX-001 gel group was superior in the majority
pared to group-based adjustments, this method allows [[f]]or of the comparisons, the KLOX LED light + KLOX-001 gel
less-biased placebo adjustment since each patient’s TWS group was also superior to SOC and KLOX-001 gel alone.
was o[[f]]fset by the estimated value that the individual patient This is seen across all treatment weeks (Figure 5) with sta-
would have achieved i[[f]] she was treated by SOC. Tukey’s
tistically signi[[f]]icant P-values for regression slopes when sub-
Least Signi[[f]]icant Difference test was used to estimate the
jected to Student’s t-test against the null hypothesis (Figure 6).
pair-wise statistical signi[[f]]icance while adjusting for mul- While interpreting TWS results, higher values correlate to
tiplicity due to the six di[[f]]ferent pair-wise comparisons for a less-favorable esthetic result, as they constitute a sum of
| each outcome every week. | [[f]]our different scales. |
A skin biopsy behind one ear was per[[f]]ormed at weeks
Due to the small sample size, no [[f]]ormal statistical analy-
ses were per[[f]]ormed on the biopsy results. The average score
Phloxine, and Eosin, Gomori Trichrome, and Luna’s methods and % o[[f]] change from baseline with the Gomori Trichrome
according to standard protocols. A thorough histopatho- [[f]]or each group was calculated, as it was the only parameter
logical examination o[[f]] the sections at weeks 0 and 12 was that did stand out clearly indicating an increase in the col-
per[[f]]ormed by an experienced pathologist blinded to the
lagen [[f]]rom baseline to week 12 that was particularly notable
treatment assignment.
(400% increase) in the group treated with the combination o[[f]]
Treatment-emergent adverse events (AEs) were summa- KLOX-001 gel [[f]]ormulation and KLOX LED light (Table 4,