Trial Outcomes & Findings for Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis (NCT NCT00470392)

Last Updated: 2016-10-05

Results Overview

Lesions were treated with either Imiquimod or Clobetasol cream. Lesions were subsequently treated with UVB and biopsied. From the biopsy samples obtained from the Imiquimod arm, quantitative PCR was performed to measure levels of Myx A, an imiquimod response gene.

Recruitment status

TERMINATED

Study phase

Target enrollment

9 participants

Primary outcome timeframe

Biopsy samples for analysis were taken 1 hour post UVB treatment

Results posted on

2016-10-05

Participant Flow

Subjects were recruited from the Dermatology clinics at University Hospitals Case Medical Center and the Louis Stokes Cleveland VAMC.

Subjects with moderate to severe psoriasis were recruited from May 2007 to July 2012. 23 subjects were screened but only 9 were assigned to a study arm and received treatment. Per protocol, subjects underwent a washout period of 1 week for topical treatments and 1 month for systemic treatments prior to pre-treatment with Imiquimod or Clobetasol.

Participant milestones

Participant milestones
Measure	Imiquimod Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Overall Study STARTED	7	2
Overall Study COMPLETED	7	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Imiquimod n=7 Participants Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol n=2 Participants Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Total n=9 Participants Total of all reporting groups
Age, Customized <=18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized Between 18 and 80 years	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Age, Customized >=80 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Biopsy samples for analysis were taken 1 hour post UVB treatment

Population: Per protocol.

Outcome measures

Outcome measures
Measure	Imiquimod n=7 Participants Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. No synchronized T cell reactivation was observed upon immunohistochemical analysis, nor upon analysis of T cell death associated gene (TDAG) mRNA by PCR, with Clobetasol treatment, so this arm was terminated.
Number of Subjects With Elevated MyxA	1 participants	—

SECONDARY outcome

Timeframe: 2 weeks after Imiquimod and UVB

Population: Per protocol.

The PASI is a disease burden measure that integrates area, erythema, thickness and scale of each target lesion. The severity score for each region is calculated by adding the scores for redness, thickness and scale (each of which are graded from 0 to 4). The maximum severity score is 12. The higher the PASI, the worse the disease. Thus, an improvement in PASI score is a lower score than the pre-treatment PASI.

Outcome measures

Outcome measures
Measure	Imiquimod n=7 Participants Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. No synchronized T cell reactivation was observed upon immunohistochemical analysis, nor upon analysis of T cell death associated gene (TDAG) mRNA by PCR, with Clobetasol treatment, so this arm was terminated.
Number of Subjects With Improvement in Lesional Psoriasis Area and Assessment (PASI) Score After Imiquimod and UVB Treatment	4 participants	—

SECONDARY outcome

Timeframe: Biopsy samples for analysis were taken 1 hour post UVB treatment

Based upon upregulated mRNA expression of MyxA in 1 out of 7 patients treated with Imiquimod, a list of alternative target genes responsive to Imiquimod was generated. The target mRNAs examined included GRAMD1A, IL2RA, TGHD1, DMXL2. The target gene was consider upregulated if there was a 1.5 fold increase in the mRNA expression of the target gene.

Outcome measures

Outcome measures
Measure	Imiquimod n=7 Participants Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. No synchronized T cell reactivation was observed upon immunohistochemical analysis, nor upon analysis of T cell death associated gene (TDAG) mRNA by PCR, with Clobetasol treatment, so this arm was terminated.
Number of Subjects With a 1.5 Fold Increase in mRNA Expression of GRAMD1A and DMXL2	1 participants	—

Adverse Events

Imiquimod

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Clobetasol

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Imiquimod n=7 participants at risk Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.	Clobetasol n=2 participants at risk Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Skin and subcutaneous tissue disorders Exacerbation of non-target psoriasis plaques during washout of topical medications	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	50.0% 1/2 • Number of events 2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Skin and subcutaneous tissue disorders Grade 4 target site reaction - blistering post UVB	28.6% 2/7 • Number of events 2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Infections and infestations Common cold	0.00% 0/7 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	50.0% 1/2 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Skin and subcutaneous tissue disorders Contact vs irritant dermatitis surrounding target sites secondary to bandages	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Skin and subcutaneous tissue disorders Grade 3 target site reaction - erythema with mild discomfort post UVB	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Skin and subcutaneous tissue disorders Exacerbation of psoriasis surrounding target sites secondary to bandages	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
General disorders Hypertension	0.00% 0/7 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	50.0% 1/2 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Skin and subcutaneous tissue disorders Burning sensation with use of study product	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.
Musculoskeletal and connective tissue disorders Right knee trauma and pain	14.3% 1/7 • Number of events 1 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.	0.00% 0/2 • Adverse event data was collected for 30 days. The investigators assessed for adverse events at each study visit.

Additional Information

Kevin D. Cooper MD

Louis Stokes VA Medical Center and University Hospitals Case Medical Center

Phone: 216 844 3111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place