Safety and Efficacy of High-Intensity Macrofocused Ultrasound for Solar Lentigo in Chinese Population: A Prospective Study
Conditions: Solar Lentigo
Sponsor: The First Affiliated Hospital with Nanjing Medical University

Project Title: Safety and Efficacy of High-Intensity Macrofocused
Ultrasound for Solar Lentigo in Chinese Population: A Prospective Study
Sponsor: The First Affiliated Hospital of Nanjing Medical University
Department: Department of Dermatology
Principal investigator: Yang Xu
Telephone: +86 13851856794
Location: Jiangsu Province Hospital, the First Affiliated Hospital of
Nanjing Medical University
ClinicalTrials.gov ID: NCT06288607
Version: 1.0
Document date: Oct. 14, 2023

I. Background
Solar Lentigo (SL), also known as solar lentigines, or age spots, is a skin disorder
associated with photoaging. It primarily appears as irregular gray or dark brown
patches with a smooth surface and clear borders. Solar lentigo commonly occur in
sun-exposed areas, such as the face, neck, hands, and forearms, potentially affecting
appearance and causing psychological stress for patients. Current treatment options
include laser, cryotherapy, chemical peeling, topical medications, and combination
therapies. Among these, laser therapies, particularly Q-switched lasers, are considered
the most effective single therapy, as they can precisely target treatment areas through
selective photothermolysis. However, this method is influenced by skin color and
carries risks of pain, redness, and hyperpigmentation.
High-Intensity Focused Ultrasound (HIFU) is a technique that focuses high-frequency
ultrasound on selected tissue areas within the body. By utilizing thermal effects,
cavitation effects, and mechanical effects, HIFU can create instantaneous
temperatures exceeding 65°C in the focal zone, stimulating collagen regeneration and
remodeling, thus achieving skin tightening. It is widely used in skin rejuvenation
treatments. Both micro- and macro-focused ultrasound have been shown to be
effective non-invasive treatments for skin rejuvenation. Recent studies have shown
that HIFU can significantly reduce UVB-induced epidermal melanin deposition, a
finding confirmed in animal models of melasma and clinical studies. This effect may
be related to the vibration and friction of the pigment caused by ultrasound,
mechanically disrupting and eliminating melanin and pigment fragments in the
superficial epidermis and dermis. Moreover, the absorption of ultrasound energy does
not rely on skin pigmentation, which can reduce adverse reactions in individuals with
darker skin tones, suggesting that HIFU may serve as an alternative treatment for
solar lentigo.
II. Objective
Primary Objective: This study aims to evaluate the efficacy and safety of
high-intensity macro-focused ultrasound in treating facial solar lentigo, as well as its
additional effects on the skin using both subjective and objective assessment methods.
III. Study Design:
This study was a prospective, single-center trial, recruited from the First Affiliated
Hospital of Nanjing Medical University from November 2023 to February 2024. This
trial was approved by the ethics committee (No. 2023-SR-708). All participants have
signed written informed consents.
The treatment involves using two ultrasound devices with different focal depths of 3.0
mm (D3.0) and 4.5 mm (D4.5) (MFUS One, Hunan Peninsula Medical Technology
Co., Ltd., China) on both sides of the face. After the procedure, an ice pack will be

applied to the treated area for 10 minutes to help reduce redness and swelling.
Follow-up visits will be scheduled at 2, 4, 6, and 8 weeks after the treatment. During
these visits, clinical images and non-invasive skin assessments will be conducted to
monitor your progress.
IV. Study Population
Inclusion Criteria:
1.adults between 18 and 70 years old, regardless of gender;
2.those who comply the clinical diagnostic criteria for solar lentigo on both sides of
the face;
3.patients understand and are willing to participate in this clinical trial and voluntarily
sign an informed consent form;
Exclusion Criteria:
1.Women who are pregnant or breastfeeding, or who plan to become pregnant during
the trial period;
2.those who are allergic to medical condensation gel;
3.those with photosensitive diseases, immune deficiencies, or those who are taking
immunosuppressants;
4.those with scar physique;
5.those with inflammatory or infectious skin diseases;
6.those who have systemically used retinoic acid in the last six months or topically
applied retinoic acid drugs in the last three months, or have a history of sun exposure
in the four weeks prior to treatment;
7.those who have undergone high-intensity focused ultrasound treatment within the
last six months;
V. Procedures
Before the treatment, a 2-3mm layer of medical cooling gel will be evenly applied to
your face. Two macro-focused handpieces with focal depths at 3.0 mm (D3.0) and 4.5
mm (D4.5) were employed on both cheeks (MFUS One, Hunan Peninsula Medical
Technology Co., Ltd., China), targeting both the lesional area and surrounding
non-lesional regions while avoiding the periorbital and perioral areas. After the
procedure, an ice pack will be applied to the treated area for 10 minutes to help reduce

redness and swelling. Follow-up visits will be scheduled at 2, 4, 6, and 8 weeks after
the treatment. During these visits, clinical images and non-invasive skin assessments
will be conducted to monitor the improvement. For non-invasive skin assessment,
skin elasticity (R-value) and transepidermal water loss (TEWL) were measured using
a Cutometer Dual MPA580 (Courage Khazaka Electronic GmbH, Köln, Germany)
and Tewameter Hex (Courage Khazaka Electronic GmbH, Köln, Germany),
respectively.
VI. Outcome Measures
1. Primary Outcome
Title: Lab* Values of Lesional Area Using Dermoscopy and ImageJ
Description: This outcome measure involves the assessment of lesional areas in
dermoscopy images, with the Lab* conversion of pigmentation intensity performed
using ImageJ software. L represents the lightness (brightness) of the lesion, where
higher L values indicate lighter lesions (improvement). a and b represent the
chromatic components (red-green and yellow-blue). Lower values in these
components indicate lighter pigmentation, while higher values suggest darker lesions.
Time Frame: week0, week2, week4, week6 and week8
2. Primary Outcome
Title: Physician Global Aesthetic Improvement Scale
Description: The Physician Global Aesthetic Improvement Scale (PGAIS) is a
5-point scale used to rate the global aesthetic improvement in appearance compared to
baseline, as judged by the investigator. The scale ranges from -1 (worsening) to 3
(very much improved). The higher score indicates the better improving effect.
Time Frame: week2, week4, week6 and week8
3. Primary Outcome
Title: Subjective Global Aesthetic Improvement Scale
Description: The Subjective Global Aesthetic Improvement Scale (SGAIS) is a
5-point scale used to rate the global aesthetic improvement in appearance compared to
baseline, as judged by the patients. The scale ranges from -1 (worsening) to 3 (very
much improved). The higher score indicates the better improving effect.
Time Frame: week2, week4, week6 and week8
4. Primary Outcome

Title: Transepidermal Water Loss (TEWL) Measurement of Lesional Area
Description: This outcome measure involves the assessment of transepidermal
water loss (TEWL), which quantifies the amount of water evaporating through the
skin. TEWL is a key indicator of skin barrier function and hydration levels. In this
study, TEWL was measured using Tewameter Hex (Courage Khazaka Electronic
GmbH) that records the rate of water loss through the skin in g/m²/h (grams per
square meter per hour). Lower TEWL values (less water loss) suggest an improved
skin barrier, which is typically the result of effective treatment and increased skin
hydration.
Time Frame: week0, week2, week4, week6 and week8
5. Primary Outcome
Title: Skin Elasticity Measurement of Lesional Area
Description: Skin elasticity was assessed using Cutometer Dual MPA580
(Courage Khazaka Electronic GmbH, Köln, Germany), which measures the skin’s
resistance to deformation and recovery after deformation. The R-value represents the
ratio of skin’s ability to resist deformation and its ability to return to its original shape
Higher R-values (greater elasticity) suggest that the skin is more resilient and can
return to its original shape after deformation, indicating healthy skin with good
elasticity and tone.
Time Frame: week0, week2, week4, week6 and week8
IV. Statistical Analysis:
For dermoscopy images, ImageJ software was utilized to perform Lab* conversion on
both the lesional and surrounding non-lesional areas. The skin elasticity (R-value),
TEWL, skin chroma (Lab* values), and Global Aesthetic Improvement Scale (GAIS)
scores were analyzed using repeated-measures analysis of variance (RM-ANOVA)
with Greenhouse-Geisser correction to evaluate the statistical significance of
treatment effects over time. When interaction effects were observed, simple effects
analysis was performed to identify the specific source of the interaction. In cases
where no interaction effects were found, the main effects were analyzed. Statistical
significance was set at p < 0.05 (two-tailed). All statistical analyses were conducted
using SPSS Statistics for Windows (version 26.0; IBM Corp.).