Clinical Trial: Effect of RANKL Inhibition on UV-induced Immunosuppression

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of RANKL Inhibition on UV-induced Immunosuppression

Brief Summary:

Ultraviolet (UV) light is part of normal sunlight and has many effects on human skin and health. One of the harmful effects of long-term UV light exposure is that it can cause skin cancer. The mechanism by which UV light causes skin cancer is not entirely understood. One of the ways UV light causes cancer is by modifying DNA molecules in the cells of the skin. Another mechanism involved in cancer formation by UV light is immunosuppression. By this mechanism, UV light inactivates cells of the immune system of the skin. The immune cells are responsible for the detection and destruction of foreign substances and organisms such as bacterias and viruses but they also recognize and destroy cancer cells. UV light is known to prevent cells of the immune system to destroy cancer cells.

In laboratory experiments, a medication called denosumab has been shown to diminish the inhibition of ultraviolet-induced suppression of skin immunity. In other words, this medication could block the effect of UV on cells of the immune system and might allow patients taking this drug to be better protected from skin cancer.

The objective of this study is to test whether denosumab blocks the immunosuppressive effect of UVB light in healthy subjects. This study is divided into two stages. In the first stage, ten subjects (Cohort 1) will be sensitized to diphenylcyclopropenone (DPCP), a topical sensitizer commonly used for the treatment of alopecia areata and cutaneous warts. By reexposing the subjects to DPCP in incremental doses, dose-response levels of cutaneous hypersensitivity reactions in normal skin will be obtained. This will allow comparison of the normal levels of DPCP-induced cutaneous hypersensitivity (CHS) reaction in non UV-exposed skin (Cohort 1) to the CHS obtained from the two UVB-exposed experimental groups of Cohort 2.

Mean dermal thickness, as measured by 20 MHz ultrasonography, after challenge with incremental doses of DPCP for subjects randomized to denosumab as compared to subjects randomized to placebo.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical score of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2 [ Time Frame: Three weeks after sensitization to DPCP. ]
    Mean clinical scores of contact hypersensitivity reaction sites elicited by incremental doses of DPCP challenges between the denosumab group and the placebo group.
  • Diameters of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2 [ Time Frame: Three weeks after sensitization to DPCP. ]
    Mean diameters (mm) of contact hypersensitivity reaction sites elicited by incremental doses of DPCP challenges between the denosumab group and the placebo group.
  • Change in dermal thickness: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2) [ Time Frame: Three weeks after sensitization to DPCP. ]
    Mean dermal thickness, as measured by 20 MHz ultrasonography, after challenge with incremental doses of DPCP for subjects previously exposed to UVB as compared to subjects non-exposed to UVB.
  • Clinical score of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2) [ Time Frame: Three weeks after sensitization to DPCP. ]
    Mean clinical scores of contact hypersensitivity reaction sites elicited by incremental doses of DPCP between UV-exposed skin and non-UV exposed skin.
  • Diameters of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2) [ Time Frame: Three weeks after sensitization to DPCP. ]
    Mean diameters of contact hypersensitivity reaction sites elicited by incremental doses of DPCP between UV-exposed skin and non-UV exposed skin.
  • Gene expression levels: denosumab group vs placebo group of Cohort 2 [ Time Frame: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure. ]
    Differences in gene expression levels of RANK, RANKL and proteins that are regulated by the RANK-RANKL interaction in the denosumab versus placebo groups.
  • Histological pattern of expression of RANKL and other proteins of interest: denosumab group vs placebo group of Cohort 2 [ Time Frame: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure. ]
    Differences in the cutaneous histological pattern of expression of RANK, RANKL and proteins and cells that are involved in RANK-RANKL interaction in the denosumab versus placebo groups.


Original Secondary Outcome: Same as current

Information By: Innovaderm Research Inc.

Dates:
Date Received: October 31, 2013
Date Started: November 2013
Date Completion:
Last Updated: July 23, 2014
Last Verified: July 2014