Skin Laxity
Conditions
Keywords
knee area, suprapatellar skin, aging, laxity
Brief summary
The human skin aging process is characterized by thinning dermis, atrophy of the extracellular matrix, and reduced collagen synthesis. Loss of collagen in the dermis is of aesthetic concern, as it is the main structural support in the dermis and its loss results in skin laxity. Photo-damaged skin, mostly due to UVR, causes degradation of elastic fibers. This is histologically seen as disorganized tangles of elastin. Additionally, as humans age, skin tends to appear more dry due to its poor hydration and turgor capacity. The use of minimally invasive aesthetic treatments in reducing signs of aging has been gaining in popularity over surgical treatments in recent years. Several energy types including, laser, radiofrequency, infrared, and ultrasound, have been developed for facial rejuvenation. These treatments induce controlled thermal damage into the dermis and cause collagen contraction and neocollagenesis resulting in skin tightening over several months. For improving appearance of other anatomical areas, micro-focused ultrasound has been the preferred method, but has shown limited success in tightening the suprapatellar skin. As with facial skin aging, the suprapatellar skin loses elasticity with age and begins to sag. Noninvasive treatments used for the face may also be used in other anatomical areas to produce the same effects of tightening. Minimally invasive bipolar radiofrequency produces a controlled thermal injury in a fractional manner without damaging the dermal-epidermal junction, epidermis or subcutis. Radiofrequency, unlike lasers, are chromophore-independent providing better penetration than lasers, and spare sweat glands, sebaceous glands, and hair follicles.
Detailed description
The Profound System is a bipolar fractional radiofrequency device which uses microneedles and thermal heat to stimulate neocollagenesis. Based on the its effect on facial skin, it can be hypothesized that bipolar fractional radiofrequency will stimulate similar effect on suprapatellar skin, lifting and reducing laxity of the skin in that region. This study intends to evaluate the effectiveness of the Profound System on suprapatellar skin, which has been FDA approved for treatment of facial wrinkles and improvement in the appearance of cellulite. This device is a well studied and frequently used on facial skin, however, there are no studies showing its effectiveness elsewhere on the body. There are alternative treatments that have been shown to decrease laxity of the suprapatellar skin, however, the studies include a small and limited population, and have not produced the desired effects in practice. The Profound device may be able to produce clinically significant improvement in laxity of the suprapatellar skin.
Interventions
DEVICEProfound system
Profound system is a bipolar fractional radiofrequency device which uses microneedles and thermal heat to stimulate neocollagenesis. Based on the its effect on facial skin, it can be hypothesized that bipolar fractional radiofrequency will stimulate similar effect on suprapatellar skin, lifting and reducing laxity of the skin in that region. Bilateral suprapatellar regions will be identified and marked for treatment.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female adults between ages 18-75 years of age. * Subjects who can read, understand, and sign the Informed Consent Form. * Subjects willing and able to comply with all study requirements * Fitzpatrick skin type I-III
Exclusion criteria
* Subjects with active localized or systemic infections. * Immunocompromised subjects. * Subjects with coagulation disorder. * History of skin photosensitivity disorders, or use of photosensitizing drugs (e.g., tetracycline or sulfa drugs). * Pregnant and/or lactating (All female volunteers will be advised about using birth control during the period of study). * In the opinion of the trained clinician, subject is unwilling or unable to adhere to all study requirements, including application and follow-up visits. * Subjects with a history of radiation therapy to the treatment area. * Subject has a history of allergy to lidocaine or ester-based local anesthetics. * Subjects with any skin pathology or condition that could interfere with evaluation or with the use of typical ancillary medical treatments or care used before, during or after treatments. * Subjects have undergone dermatological procedures (e.g., laser or light treatments) for the treatment of wrinkles, skin resurfacing, or skin rejuvenation in the treatment area within 1 year of study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Photographic Knee Laxity and Texture Evaluation | baseline and 6 months | Photographs will be used to evaluate efficacy of treatment. The photographs from final visit will be compared to their baseline photographs and visually evaluated by the study team. The study team will assess the laxity from baseline to 6 months. |
| Epidermal Thickness | baseline, 7 Days, 3 Weeks, 3 Months and 6 Months | Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. |
| Dermal Thickness | Baseline, 7 Days, 3 Weeks, 3 Months and 6 Months | Dermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. |
| Change in Blood Flow at 0.25mm | Baseline, Day 7, Week 3 Month 3 and Month 6 | Blood Flow will be measured via optical coherence tomography prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. |
| Transepidermal Water Loss | Baseline, Day 7, Week 3, Month 3 and Month 6 | Transepidermal Water Loss will be masured via Aquaflux prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. |
| Skin Elasticity | Baseline, Day 7, Week 3, Months 3 and Months 6 | Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. |
| Change in Skin Laxity | baseline, 7 days, 3 weeks, 3 months and 6 months | BTC2000 will be used to measure skin laxity prior to treatment and post treatment. The BTC2000 is a non-invasive device that measures skin laxity by creating a negative pressure against the skin and calculates laxity when the pressure is released. |
| Histological Analysis- Collagen 1 | Baseline. Day 7 and 3 Months | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. |
| Gene Expression- Collagen 1 | Day 7, Month 3 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change was calculated at each time point past baseline. Fold change = sample/average of the baseline. |
| Epidermal Density | Baseline, Day 7, Week 3, Month 3 and Month 6 | Epidermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame. |
| Histological Analysis- Collagen 3 | Baseline, Day 7, Month 3 | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Sample/Average of the baseline. |
| Histological Analysis- Elastin | Baseline, Day 7, Month 3 | Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Samples/Average of the baseline |
| Gene Expression- Collagen 3 | Day 7, Month 3 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. |
| Gene Expression- Elastin | Day 7, Month 3 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. |
| Gene Expression- Interluekin 6 | Day 7, Month 3 | Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment All patients will undergo treatment with Profound system device (bipolar fractional radiofrequency device which uses microneedles and thermal heat to stimulate neocollagenesis). Using the radiofrequency and temperature setting within the FDA approved limits (460 +/- 5kHz and 65-75°C +/- 1°C), patients will be treated one time over the entire suprapatellar region bilaterally and followed for a 6 month period. The acute effect of the radiofrequency application will be determined by subjective and objective analysis using standard, close-up, 3D, cross-polarized, high resolution ultrasound, optical coherence tomography, transepidermal water loss measurements, and/or BTC 2000 measurements.
Biopsies will be taken using 0.33mm WellTech Rapid Core 0.33mm Biopsy Punch. Biopsies will allow investigators to correlate changes seen in skin measurements with histology and gene expression. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 4 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Change in Blood Flow at 0.25mm
Blood Flow will be measured via optical coherence tomography prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment.
Time frame: Baseline, Day 7, Week 3 Month 3 and Month 6
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in Blood Flow at 0.25mm | Baseline | 0.3294 mm/s | Standard Deviation 0.009815 |
| Treatment | Change in Blood Flow at 0.25mm | Day 7 | 0.23 mm/s | Standard Deviation 0.41 |
| Treatment | Change in Blood Flow at 0.25mm | Week 3 | -0.02 mm/s | Standard Deviation 0.37 |
| Treatment | Change in Blood Flow at 0.25mm | Month 3 | 0.080534 mm/s | Standard Deviation 0.33661 |
| Treatment | Change in Blood Flow at 0.25mm | Month 6 | 0.1045 mm/s | Standard Deviation 0.3411 |
Primary
Change in Skin Laxity
BTC2000 will be used to measure skin laxity prior to treatment and post treatment. The BTC2000 is a non-invasive device that measures skin laxity by creating a negative pressure against the skin and calculates laxity when the pressure is released.
Time frame: baseline, 7 days, 3 weeks, 3 months and 6 months
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in Skin Laxity | Day 7 | 12.5364 mm | Standard Deviation 27.762 |
| Treatment | Change in Skin Laxity | Week 3 | 3.75791 mm | Standard Deviation 21.921 |
| Treatment | Change in Skin Laxity | Month 3 | 0.85623 mm | Standard Deviation 21.253 |
| Treatment | Change in Skin Laxity | Month 6 | -5.54778 mm | Standard Deviation 16.383 |
| Treatment | Change in Skin Laxity | Baseline | 0.7408 mm | Standard Deviation 0.1200845 |
Primary
Dermal Thickness
Dermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame.
Time frame: Baseline, 7 Days, 3 Weeks, 3 Months and 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Dermal Thickness | Baseline | 1104.7 mm | Standard Deviation 192.626 |
| Treatment | Dermal Thickness | Day 7 | 1179.2 mm | Standard Deviation 177.83 |
| Treatment | Dermal Thickness | Week 3 | 1241.367 mm | Standard Deviation 191.049 |
| Treatment | Dermal Thickness | Month 3 | 1167.933 mm | Standard Deviation 150.659 |
| Treatment | Dermal Thickness | Month 6 | 1122.233 mm | Standard Deviation 200.07 |
Primary
Epidermal Density
Epidermal thickness will be masured via high resolution ultrasound prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame.
Time frame: Baseline, Day 7, Week 3, Month 3 and Month 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Epidermal Density | Baseline | 0.00380558 um | Standard Deviation 0.000635 |
| Treatment | Epidermal Density | Day 7 | 0.028518 um | Standard Deviation 0.09374 |
| Treatment | Epidermal Density | Week 3 | 0.004336 um | Standard Deviation 0.00232 |
| Treatment | Epidermal Density | Month 3 | 0.020107 um | Standard Deviation 0.08714 |
| Treatment | Epidermal Density | Month 6 | 0.00392152 um | Standard Deviation 2.783 |
Primary
Epidermal Thickness
Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame.
Time frame: baseline, 7 Days, 3 Weeks, 3 Months and 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Epidermal Thickness | Baseline | 96.53333 mm | Standard Deviation 10.2578 |
| Treatment | Epidermal Thickness | 7 Days | 106.9 mm | Standard Deviation 24.0632 |
| Treatment | Epidermal Thickness | 3 Weeks | 98.33333 mm | Standard Deviation 16.3524 |
| Treatment | Epidermal Thickness | 3 Months | 92.36667 mm | Standard Deviation 9.55739 |
| Treatment | Epidermal Thickness | 6 Months | 91.36667 mm | Standard Deviation 12.1414 |
Primary
Gene Expression- Collagen 1
Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change was calculated at each time point past baseline. Fold change = sample/average of the baseline.
Time frame: Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Gene Expression- Collagen 1 | Day 7 | 1.91 fold change | Standard Error 1.68 |
| Treatment | Gene Expression- Collagen 1 | Month 3 | 1.38 fold change | Standard Error 0.57 |
Primary
Gene Expression- Collagen 3
Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline.
Time frame: Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Gene Expression- Collagen 3 | Day 7 | 2.07 fold change | Standard Error 1.68 |
| Treatment | Gene Expression- Collagen 3 | Month 3 | 1.36 fold change | Standard Error 0.96 |
Primary
Gene Expression- Elastin
Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline.
Time frame: Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Gene Expression- Elastin | Day 7 | 0.89 fold change | Standard Error 0.41 |
| Treatment | Gene Expression- Elastin | Month 3 | 1.74 fold change | Standard Error 1.37 |
Primary
Gene Expression- Interluekin 6
Biopsies of the treated are will be taken prior to treatment and post treatment for gene expression analysis. This analysis will identify gene expression related to collagen formation and increased cell turnover. Fold change = sample/average of the baseline.
Time frame: Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Gene Expression- Interluekin 6 | Day 7 | 18.60 fold change | Standard Error 13.37 |
| Treatment | Gene Expression- Interluekin 6 | Month 3 | 4.04 fold change | Standard Error 4.78 |
Primary
Histological Analysis- Collagen 1
Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame.
Time frame: Baseline. Day 7 and 3 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Histological Analysis- Collagen 1 | Day 7 | 1.00 fluorescence intensity | Standard Deviation 0.23 |
| Treatment | Histological Analysis- Collagen 1 | Month 3 | 1.04 fluorescence intensity | Standard Deviation 0.23 |
| Treatment | Histological Analysis- Collagen 1 | Baseline | 1.38 fluorescence intensity | Standard Deviation 0.51 |
Primary
Histological Analysis- Collagen 3
Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Sample/Average of the baseline.
Time frame: Baseline, Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Histological Analysis- Collagen 3 | Baseline | 0.63 fluorescence intensity | Standard Deviation 0.17 |
| Treatment | Histological Analysis- Collagen 3 | Day 7 | 0.72 fluorescence intensity | Standard Deviation 0.18 |
| Treatment | Histological Analysis- Collagen 3 | Month 3 | 0.71 fluorescence intensity | Standard Deviation 0.28 |
Primary
Histological Analysis- Elastin
Relative changes in protein abundance in biopsies taken at post treatment compare to control or entreated group will be quantified using an image processing software based on fluorescence signal intensity. The change from baseline was calculated at each time frame. Samples/Average of the baseline
Time frame: Baseline, Day 7, Month 3
Population: Results at each visit show the change from baseline values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Histological Analysis- Elastin | Month 3 | 0.58 fluorescence intensity | Standard Deviation 0.17 |
| Treatment | Histological Analysis- Elastin | Baseline | 1.29 fluorescence intensity | Standard Deviation 0.24 |
| Treatment | Histological Analysis- Elastin | Day 7 | 0.90 fluorescence intensity | Standard Deviation 0.5 |
Primary
Photographic Knee Laxity and Texture Evaluation
Photographs will be used to evaluate efficacy of treatment. The photographs from final visit will be compared to their baseline photographs and visually evaluated by the study team. The study team will assess the laxity from baseline to 6 months.
Time frame: baseline and 6 months
Population: Reviewers were asked to evaluate the visible change in texture and laxity on a scale of 1-3. Worsened (1), No Change (2) and Improved (3).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Photographic Knee Laxity and Texture Evaluation | Texture | 1.87 score on a scale | Standard Deviation 0.52 |
| Treatment | Photographic Knee Laxity and Texture Evaluation | Laxity | 2.02 score on a scale | Standard Deviation 0.52 |
Primary
Skin Elasticity
Skin Elasticity will be measured via BTC2000 prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame.
Time frame: Baseline, Day 7, Week 3, Months 3 and Months 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Skin Elasticity | Baseline | 0.80199 mm | Standard Deviation 0.1263 |
| Treatment | Skin Elasticity | Day 7 | 0.811731094 mm | Standard Deviation 0.256170747 |
| Treatment | Skin Elasticity | Week 3 | 0.82434 mm | Standard Deviation 0.1549 |
| Treatment | Skin Elasticity | Month 3 | 0.77234 mm | Standard Deviation 0.11494 |
| Treatment | Skin Elasticity | Month 6 | 0.74615 mm | Standard Deviation 0.11275 |
Primary
Transepidermal Water Loss
Transepidermal Water Loss will be masured via Aquaflux prior to treatment (baseline), 7 days, 3 weeks, 3 months and 6 months post treatment. The change from baseline was calculated at each time frame.
Time frame: Baseline, Day 7, Week 3, Month 3 and Month 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Transepidermal Water Loss | Baseline | 9.379 g/(m2h) | Standard Deviation 2.05288 |
| Treatment | Transepidermal Water Loss | Day 7 | 9.6007 g/(m2h) | Standard Deviation 2.1681 |
| Treatment | Transepidermal Water Loss | Week 3 | 10.9986 g/(m2h) | Standard Deviation 3.9201 |
| Treatment | Transepidermal Water Loss | Month 3 | 11.744 g/(m2h) | Standard Deviation 8.7825 |
| Treatment | Transepidermal Water Loss | Month 6 | 8.772 g/(m2h) | Standard Deviation 1.966 |