Retinol on Human Skin Aging in East Asian Descent

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02906566
• Collaborator: (none)
• Enrollment: 110
• Location: 1
• Arms: 2
• Duration (Months): 28.2
• Patients Per Site Per Month: 3.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intrinsic Aging of Skin	Drug: Retinol; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Discovery of Effects of Retinol on Human Skin Aging in Individuals of East Asian Descent
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Mar 9, 2018
• Actual Study Completion Date: Mar 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Older Group Ages 55-75 Active and Placebo. Participants received retinol lotion on one arm and placebo to match on the other arm.	Drug: Retinol; Retinol in the form of vitamin A lotion; Drug: Placebo; Placebo of Retinol
No Intervention: Young Group Ages 18-25 Participants in the group will give tissue sample only for comparison.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. Transepidermal Water Loss [Baseline; Week 12]

   Transepidermal Water Loss of arm skin was measured in units of grams/hours/meters squared.

2. 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).

3. Elasticity on Arm Skin [Baseline; week 12]

   Elasticity was assessed using cutometry (R2 curve) as millimeters per second

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Dermatology	Redwood City	California	United States	94603

Sponsors and Collaborators

• Stanford University

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 12, 2016

More Information

Publications

None provided.

• Responsible Party: Anne Chang, Associate Professor of Dermatology, Stanford University
• ClinicalTrials.gov Identifier: NCT02906566
• Other Study ID Numbers: 33762
• First Posted: Sep 20, 2016
• Last Update Posted: Apr 16, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Vitamin A

Study Results

Participant Flow

Pre-assignment Detail	110 participants were consented; 34 participants were assigned to a study arm.

Arm/Group Title	Older Group Ages 55-75	Young Group Ages 18-25
Arm/Group Description	Participants received retinol lotion on one arm and placebo to match on the other arm.	Participants in the group will give a tissue sample from one arm only for comparison.
Period Title: Overall Study
STARTED	24	10
COMPLETED	21	10
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Older Group Ages 55-75	Young Group Ages 18-25	Total
Arm/Group Description	Participants received retinol lotion on one arm and placebo to match on the other arm.	Participants in the group will give a tissue sample from one arm only for comparison.	Total of all reporting groups
Overall Participants	24	10	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 45.8%	10 100%	21 61.8%
>=65 years	13 54.2%	0 0%	13 38.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (4.7)	21.7 (3.1)	51.7 (21.5)
Sex: Female, Male (Count of Participants)
Female	24 100%	10 100%	34 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	24 100%	10 100%	34 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%	10 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Older Group, Retinol Versus Placebo)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Older Group Ages 55-75
Arm/Group Description	Participants received retinol lotion on one arm and placebo to match on the other arm.
Measure Participants	24
Measure genes	56615
Upregulated	23
Downregulated	21

2. Secondary Outcome

Title	Transepidermal Water Loss
Description	Transepidermal Water Loss of arm skin was measured in units of grams/hours/meters squared.
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Retinol Treated Arm	Placebo Treated Arm
Arm/Group Description	Participants in the older group (ages 55-75), retinol arm.	Participants in the older group (ages 55-75), placebo arm.
Measure Participants	21	21
Baseline	17.1 (10.2)	16.2 (11.7)
Week 12	9.4 (6.7)	10.2 (6.1)

3. Secondary Outcome

Title	Severity of Arm Skin Wrinkling
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Retinol Treated Arm	Placebo Treated Arm
Arm/Group Description	Participants in the older group (ages 55-75), retinol arm.	Participants in the older group (ages 55-75), placebo arm.
Measure Participants	20	20
Baseline	5.15 (1.96)	5.5 (1.59)
Week 12	4.85 (1.79)	5.175 (1.28)

4. Secondary Outcome

Title	Elasticity on Arm Skin
Description	Elasticity was assessed using cutometry (R2 curve) as millimeters per second
Time Frame	Baseline; week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	Retinol Treated Arm	Placebo Treated Arm
Arm/Group Description	Participants in the older group (ages 55-75), retinol arm.	Participants in the older group (ages 55-75), placebo arm.
Measure Participants	21	21
Baseline	0.8623 (0.0791)	0.8753 (0.0464)
Week 12	0.8587 (0.0655)	0.8576 (0.0684)

5. Secondary Outcome

Title	Count of Participants With Skin and Subcutaneous Adverse Events as a Measure of Type and Severity of Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Retinol Treated Arm	Placebo Treated Arm
Arm/Group Description	Participants in the older group (ages 55-75), retinol arm.	Participants in the older group (ages 55-75), placebo arm.
Measure Participants	21	21
Dermatitis (Grade 1)	1 4.2%	1 10%
Tingling sensation after application (Grade 1)	0 0%	1 10%

6. Primary Outcome

Title	Number of Genes Upregulated or Downregulated as Assessed by RNA Sequencing (Younger Group Versus Older Group as Baseline)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Young Group Ages 18-25
Arm/Group Description	Participants in the group will give a tissue sample from one arm only for comparison.
Measure Participants	10
Measure genes	56615
Downregulated	775
Upregulated	587

Adverse Events

Time Frame	Up to 12 weeks.
Arm/Group Title	Older Group Ages 55-75		Young Group Ages 18-25
Arm/Group Description	Participants received retinol lotion on one arm and placebo to match on the other arm.		Participants in the group will give a tissue sample from one arm only for comparison.
All Cause Mortality
	Older Group Ages 55-75		Young Group Ages 18-25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/10 (0%)
Serious Adverse Events
	Older Group Ages 55-75		Young Group Ages 18-25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Older Group Ages 55-75		Young Group Ages 18-25
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)		0/10 (0%)
Infections and infestations
Upper respiratory infection	3/24 (12.5%)	4	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/24 (8.3%)	2	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.