Intrinsic Aging of Skin
Conditions
Brief summary
There has been increasing evidence for different rates of natural aging in humans and one of the best organs to study human aging is skin. Studies have demonstrated anti-aging effects of topical agents (such as creams, gels, lotions, or ointments) and one of them, retinol or vitamin A, was shown to decrease fine wrinkling in skin of older individuals. Additionally, studies of retinol in humans have largely occurred in white populations and so this study aims to focus on skin aging in individuals of East Asian descent as they represent a majority of the world population. This study aims to better characterize the molecular basis of rejuvenation effects and to potentially discover new topical agents with similar and/or more effective preservation of skin youthfulness.
Interventions
DRUGRetinol
Retinol in the form of vitamin A lotion
DRUGPlacebo
Placebo of Retinol
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* able to provide written informed consent * older group: age between 50 and 75 years * young group: age 18 to 25 years * all four grandparents of Han Chinese, Japanese, Korean descent * body mass index within normal or overweight range * no history of weight loss of \>20 lbs within past 5 years
Exclusion criteria
* skin condition in the areas of skin biopsy that would obscure results of analysis * topical creams or treatment to arms 2 weeks prior to study baseline visit * individuals with known hypersensitivity to retinoid class of agents (older group only) * prior anti-aging treatments to arms including retinol, microdermabrasion within 2 weeks of baseline visit * prior laser therapy or surgical procedure to arms * prior radiation or other trauma (extensive burns or abrasions) to arm skin * hormone-based therapy within 4 weeks of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Older Group, Retinol Versus Placebo) | Week 12 | Differences in transcript levels are reported as the number that were upregulated or downregulated in the participant's retinol-treated arm versus their placebo-treated arm. |
| Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Younger Group Versus Older Group as Baseline) | Week 1 | Differences in transcript levels are reported as the number of genes that were upregulated or downregulated in the Younger Group participant tissue samples, as compared to a baseline provided by tissue samples collected from the Older Group (prior to their treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transepidermal Water Loss | Baseline; Week 12 | Transepidermal Water Loss of arm skin was measured in units of grams/hours/meters squared. |
| Severity of Arm Skin Wrinkling | Baseline; Week 12 | Wrinkling was assessed by the investigator using a 10-point Likert scale (range 0 to 9, lower scores correspond to less wrinkling). |
| Elasticity on Arm Skin | Baseline; week 12 | Elasticity was assessed using cutometry (R2 curve) as millimeters per second |
| Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events | Baseline through week 12 | Skin and subcutaneous adverse events were assessed for this outcome and documented and scored according to CTCAE version 4.03. |
Countries
United States
Participant flow
Pre-assignment details
110 participants were consented; 34 participants were assigned to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Older Group Ages 55-75 Participants received retinol lotion on one arm and placebo to match on the other arm. | 24 |
| Young Group Ages 18-25 Participants in the group will give a tissue sample from one arm only for comparison. | 10 |
| Total | 34 |
Baseline characteristics
| Characteristic | Young Group Ages 18-25 | Total | Older Group Ages 55-75 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 13 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 21 Participants | 11 Participants |
| Age, Continuous | 21.7 years STANDARD_DEVIATION 3.1 | 51.7 years STANDARD_DEVIATION 21.5 | 66 years STANDARD_DEVIATION 4.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 34 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 Participants | 34 Participants | 24 Participants |
| Sex: Female, Male Female | 10 Participants | 34 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 10 |
| other Total, other adverse events | 4 / 24 | 0 / 10 |
| serious Total, serious adverse events | 0 / 24 | 0 / 10 |
Outcome results
Primary
Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Older Group, Retinol Versus Placebo)
Differences in transcript levels are reported as the number that were upregulated or downregulated in the participant's retinol-treated arm versus their placebo-treated arm.
Time frame: Week 12
Population: Participants in the Young Group Ages 18-25 attended a single study visit at week 1 to provide tissue samples for comparison purposes, and are not included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Older Group Ages 55-75 | Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Older Group, Retinol Versus Placebo) | Upregulated | 23 genes |
| Older Group Ages 55-75 | Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Older Group, Retinol Versus Placebo) | Downregulated | 21 genes |
Primary
Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Younger Group Versus Older Group as Baseline)
Differences in transcript levels are reported as the number of genes that were upregulated or downregulated in the Younger Group participant tissue samples, as compared to a baseline provided by tissue samples collected from the Older Group (prior to their treatment).
Time frame: Week 1
Population: Only the participants in Younger Group (ages 18-25) are included in the analysis, since a comparison of the baseline data for the Older Group (ages 55-75) against itself is not clinically meaningful.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Older Group Ages 55-75 | Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Younger Group Versus Older Group as Baseline) | Downregulated | 775 genes |
| Older Group Ages 55-75 | Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Younger Group Versus Older Group as Baseline) | Upregulated | 587 genes |
Secondary
Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events
Skin and subcutaneous adverse events were assessed for this outcome and documented and scored according to CTCAE version 4.03.
Time frame: Baseline through week 12
Population: Participants in the Young Group Ages 18-25 attended a single study visit at week 1 to provide tissue samples for comparison purposes, and are not included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Older Group Ages 55-75 | Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events | Dermatitis (Grade 1) | 1 Participants |
| Older Group Ages 55-75 | Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events | Tingling sensation after application (Grade 1) | 0 Participants |
| Placebo Treated Arm | Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events | Dermatitis (Grade 1) | 1 Participants |
| Placebo Treated Arm | Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events | Tingling sensation after application (Grade 1) | 1 Participants |
Secondary
Elasticity on Arm Skin
Elasticity was assessed using cutometry (R2 curve) as millimeters per second
Time frame: Baseline; week 12
Population: Participants in the Young Group Ages 18-25 attended a single study visit at week 1 to provide tissue samples for comparison purposes, and are not included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Group Ages 55-75 | Elasticity on Arm Skin | Baseline | 0.8623 millimeters per second | Standard Deviation 0.0791 |
| Older Group Ages 55-75 | Elasticity on Arm Skin | Week 12 | 0.8587 millimeters per second | Standard Deviation 0.0655 |
| Placebo Treated Arm | Elasticity on Arm Skin | Baseline | 0.8753 millimeters per second | Standard Deviation 0.0464 |
| Placebo Treated Arm | Elasticity on Arm Skin | Week 12 | 0.8576 millimeters per second | Standard Deviation 0.0684 |
Secondary
Severity of Arm Skin Wrinkling
Wrinkling was assessed by the investigator using a 10-point Likert scale (range 0 to 9, lower scores correspond to less wrinkling).
Time frame: Baseline; Week 12
Population: Participants in the Young Group Ages 18-25 attended a single study visit at week 1 to provide tissue samples for comparison purposes, and are not included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Group Ages 55-75 | Severity of Arm Skin Wrinkling | Baseline | 5.15 units on a scale | Standard Deviation 1.96 |
| Older Group Ages 55-75 | Severity of Arm Skin Wrinkling | Week 12 | 4.85 units on a scale | Standard Deviation 1.79 |
| Placebo Treated Arm | Severity of Arm Skin Wrinkling | Baseline | 5.5 units on a scale | Standard Deviation 1.59 |
| Placebo Treated Arm | Severity of Arm Skin Wrinkling | Week 12 | 5.175 units on a scale | Standard Deviation 1.28 |
Secondary
Transepidermal Water Loss
Transepidermal Water Loss of arm skin was measured in units of grams/hours/meters squared.
Time frame: Baseline; Week 12
Population: Participants in the Young Group Ages 18-25 attended a single study visit at week 1 to provide tissue samples for comparison purposes, and are not included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Group Ages 55-75 | Transepidermal Water Loss | Baseline | 17.1 g/h/m^2 | Standard Deviation 10.2 |
| Older Group Ages 55-75 | Transepidermal Water Loss | Week 12 | 9.4 g/h/m^2 | Standard Deviation 6.7 |
| Placebo Treated Arm | Transepidermal Water Loss | Week 12 | 10.2 g/h/m^2 | Standard Deviation 6.1 |
| Placebo Treated Arm | Transepidermal Water Loss | Baseline | 16.2 g/h/m^2 | Standard Deviation 11.7 |