Trial Outcomes & Findings for An Assessment of TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light (NCT NCT05398237)

Last Updated: 2024-09-24

Results Overview

The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TLR4 signaling pathway (AKT S473, AKT T308, IkBa S32/36, IRAK2, IRF-3, IRF-3 S386, MyD88, TAK1 S412, TBK1/NAK, TLR4, TRAF3, TRAF6, TRIF, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.

Recruitment status

COMPLETED

Study phase

Target enrollment

31 participants

Primary outcome timeframe

Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).

Results posted on

2024-09-24

Participant Flow

Participant milestones

Participant milestones
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Overall Study STARTED	31
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

An Assessment of TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light n=30 Participants We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants
Sun Damaged Skin Mild	10 Participants n=5 Participants
Sun Damaged Skin Moderate	10 Participants n=5 Participants
Sun Damaged Skin Severe	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).

Outcome measures

Outcome measures
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light n=28 Participants We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Number of TLR4 Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure) Number of analytes with significant change from baseline to 1 hour post-SSL	5 Number of analytes
Number of TLR4 Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure) Number of analytes with significant change from baseline to 24 hours post-SSL	11 Number of analytes

PRIMARY outcome

Timeframe: Changes from baseline (pre-SSL exposure) to post-SSL exposure (at 1hr and 24hr post-exposure).

Population: There are multiple pre-specified analytes in the TOPK/PRPK pathway. For each pre-specified analyte in a pathway, a paired t-test is applied to compare the log2 expression level between baseline and post-SSL time point, and the total number of analytes significantly different at the 0.05 level (with change in the expected direction) serves as the test statistic, with its null distribution estimated by randomly permuting the within-subject pre-/post-SSL labels 10,000 times.

The number of pre-specified Reverse Phase Protein Microarray Analysis (RPPA) analytes in the TOPK/PRPK signaling pathway (p90RSK S380, PBK/TOPK, PRPK, ERK 1/2 T202/Y204, c-Jun, c-Jun S63, c-Jun S73, NFkB p65 S536, and p38 MAPK T180/Y182) that had a significant change from pre-solar simulated light (pre-SSL) exposure (baseline) to 1hr and 24hr post-SSL in epidermis of sun damaged skin. This outcome will be used to test whether there was a change at the pathway level using the pathway analysis method based on a self-contained, subject-level permutation test: for each analyte a paired t-test is applied to compare the log2 expression level between baseline and the post-SSL time point, and the total number of analytes significantly different at the 0.05 level with change in the expected direction serves as the test statistic, with its null distribution to be estimated by subject-level permutation.

Outcome measures

Outcome measures
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light n=28 Participants We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Number of TOPK/PRPK Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure) Number of analytes with significant change from baseline to 1 hour post-SSL	4 Number of analytes
Number of TOPK/PRPK Signaling Pathway Analytes With a Significant Change in Expression From Baseline (Pre-solar Stimulated Light Exposure to 1 and 24 Hours Post Exposure) Number of analytes with significant change from baseline to 24 hours post-SSL	5 Number of analytes

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-SSL exposure) and post-SSL exposure (at 5hr and 24hr post-exposure).

The exploratory analyses will associate the sun damage score/severity level with analyte activation in the sun damage samples. Based on these analyses, the most appropriate post-solar simulated light time point (per pathway) will be selected based on the combination with the largest effect sizes. Furthermore, an exploratory systems biology analysis will be conducted based on these analyses; one post-SSL time point (per pathway) will be selected for future studies based on the combination with the largest effect sizes.

Outcome measures

Outcome data not reported

Adverse Events

TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	TLR4 and TOPK/PRPK Signaling in Sun Damaged Human Skin Acutely Exposed to Solar Simulated Light n=30 participants at risk We have one arm, which consists of participants with a broad range of sun damage on the forearm. Based on the standardized clinical photodamage scale (Hu C, Curiel-Lewandrowski C. Archives of Dermatology, 2011; 147(1):31-36), we will include mild (N=12), moderate (N=12), and severely (N=12) sun damaged skin. Solar Simulated Light (SSL): Acute SSL will be delivered to sun damaged skin at a rate of two-times the minimal erythema dose of each individual subject. Minimal erythema dose is defined as the smallest dose of energy necessary to produce confluent erythema with four distinct borders at 22-26 hours post-exposure.
Injury, poisoning and procedural complications Swelling	3.3% 1/30 • Number of events 1 • Adverse event data was collected through study completion, an average of 4 weeks
Injury, poisoning and procedural complications Pain at biopsy site	10.0% 3/30 • Number of events 4 • Adverse event data was collected through study completion, an average of 4 weeks
Injury, poisoning and procedural complications Erythema	3.3% 1/30 • Number of events 1 • Adverse event data was collected through study completion, an average of 4 weeks
Skin and subcutaneous tissue disorders Pruritis	3.3% 1/30 • Number of events 1 • Adverse event data was collected through study completion, an average of 4 weeks

Additional Information

Clara Curiel-Lewandrowski, MD

University of Arizona Cancer Center

Phone: (520) 626-5351

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place