Photodynamic Therapy-Induced Immune Modulation: Part III

This study is designed as a double-blinded proof of concept of feasibility study to define if the immunosuppression associated with photodynamic therapy (PDT) can be blocked by treatment with cyclo-oxygenase-2 (COX-2) inhibitor celecoxib in comparison to placebo. PDT consists of application of the photosensitizer 5-aminolevulinic acid followed by treatment with a blue light. PDT is used to treat pre-cancerous actinic keratosis on large areas of skin. These studies are a continuation of ongoing studies that indicate that the lipid mediator platelet-activating factor (PAF) is generated in skin following PDT, and that PDT suppresses the immune system. It is hypothesized that PDT-generated PAF results in the immunosuppression associated with PDT. Therefore, it is proposed that a treatment to block that immunosuppression could protect the patient undergoing PDT. Blockers of the PAF system are not currently commercially available. However research studies done at Wright State University using mice indicate that PAF- and PDT-induced immunosuppression is blocked by treatment with COX-2 inhibitors. This study is conducted as a proof of concept.

Study length and visit for subjects with actinic keratoses: The first part of the study is completed in 12 days then there are follow up visits at 6 and 12 months. There are a total of 6 separate visits to the research office.

Study length and visit for control subjects: The study is completed in 10 days. There are a total of 4 separate visits to the research office.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis; Photodynamic Therapy
• Intervention / Treatment: Drug: Celecoxib 200mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Fairborn, Ohio, United States, 45324
      • Wright State Physicians

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Control Subjects:

• Adult age 45 or older
• Caucasian (Fair skin, Fitzpatrick types I and II)
• Ability to understand and consent to the instructions of the study
• Have access to stable transportation

Inclusion Criteria for Study Subjects:

• Wright State University dermatologist has prescribed PDT for the treatment of actinic damage (Presence of precancerous actinic keratoses whose treatment necessitates PDT with the BLU-U).
• Undergoing PDT on greater than 5% body surface area: face and scalp, face and dorsal surface of arms, face and chest, face and back, or dorsal surface of arms alone, chest alone, or back alone.
• Caucasian (Fair skin, Fitzpatrick types I and II)
• Adult-age 45 or older
• Ability to understand the informed consent and comply with instructions and have stable transportation.

Exclusion Criteria for All Subjects:

• PDT on less than 5% body surface area (eg, forehead)
• Present treatment with corticosteroids or Non-steroidal inflammatory drugs (e.g., cyclooxygenase inhibitors) within past 2 months (except low-dose 81 mg aspirin).
• On antioxidant supplements (e.g., vitamin C) for past 2 months
• Tanning bed use within last 3 months
• PDT treatments within last 3 months
• Significant health issues that could affect the immune system (e.g., uncontrolled Diabetes Mellitus, Rheumatoid arthritis, skin rashes, psoriasis) that could interfere with testing
• Pregnant or nursing
• No immunosuppression, and on no immunosuppressive medications or NSAIDS within past 30 days (except low-dose [81 mg daily] aspirin).
• No significant underlying diseases that could potentially interfere with the immune assays or cardiac or renal or liver problems.
• History of blood clot or hypercoagulable state or GI bleed/ulceration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PDT + Celecoxib; Patient receiving PDT taking 200mg celecoxib.	Drug: Celecoxib 200mg; 14 Celecoxib 200mg taken 1 in the morning and 1 in the evening.
Placebo Comparator: PDT + Placebo; Patient receiving PDT taking placebo.	Drug: Placebo; 14 placebo capsules taken 1 in the morning and 1 in the evening.
Active Comparator: Control + Celecoxib; Control subject not receiving PDT taking 200mg celecoxib.	Drug: Celecoxib 200mg; 14 Celecoxib 200mg taken 1 in the morning and 1 in the evening.
Placebo Comparator: Control + Placebo; Control subject not receiving PDT taking placebo.	Drug: Placebo; 14 placebo capsules taken 1 in the morning and 1 in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Photodynamic Therapy (PDT)-induced Systemic Immunosuppression From Baseline with Celecoxib Treatment.	Investigator will assess change through clinical laboratory values and reactions to skin testing.	Day 7
Change From Baseline in the Number of Actinic Keratosis at 6 months.	Investigator will assess the number of actinic keratosis in the PDT-treated areas.	6 Months
Change From Baseline in the Number of Actinic Keratosis at 12 months.	Investigator will assess the number of actinic keratosis in the PDT-treated areas.	12 Months

Collaborators and Investigators

• Sponsor: Wright State University
• Investigators: Principal Investigator: Jeffrey B Travers, MD, PhD, Wright State University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): March 21, 2023
• Study Completion (Actual): March 21, 2023

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Actinic Keratosis; Photodynamic Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: 06499

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes