The Effect of Topical Imipramine on Photodynamic Therapy-Mediated Immunosuppression on Forearms or Face on US Veterans

Acid Sphingomyelinase Inhibition to Mitigate the Environmental Exposure Risks of Ultraviolet Light-Induced Actinic Neoplasia and Squamous Cell Carcinoma in US Veterans

The purpose of this study is to test the use of topical imipramine in combination with topical photodynamic therapy's (PDT) effect on the effectiveness and pain immunosuppression following treatment. PDT is a commonly used treatment in dermatology for patients who have many pre-cancers (actinic keratosis or "AK") on their skin. These are both FDA-approved medications, but this study is evaluating their use in combination, which has not been evaluated in the past. The investigators have been doing studies using mice that suggest imipramine might reduce immune system suppression by PDT thus allowing it to work better. Subjects whose provider has decided that they may benefit from PDT to treat their skin due to many AK precancerous lesions will be recruited for this study. Please note that the PDT itself is not experimental, only the imipramine treatment to the skin. There is a separate informed consent for the PDT.

Study Overview

• Status: Recruiting
• Conditions: Actinic Keratosis; Photodynamic Therapy; Imipramine
• Intervention / Treatment: Drug: Imipramine; Other: Control Vehicle

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Craig A Rohan, MD; Phone Number: (937) 245-7500; Email: craig.rohan@va.gov
• Study Contact Backup: Name: Jeffrey Travers, MD; Phone Number: 2026 (937) 268-6511; Email: Jeffrey.Travers@va.gov

Study Locations

• United States
  • Ohio
    • Dayton, Ohio, United States, 45428
      • Recruiting
      • Dayton VA Medical Center, Dayton, OH
      • Principal Investigator: Jeffrey Travers, MD
      • Contact: Elizabeth Cates, MPA; Phone Number: (937) 245-7500; Email: elizabeth.cates@wrightstatephysicians.org
      • Contact: Christina B Knisely, MPH; Phone Number: (937) 724-7500; Email: Christina.knisely@wright.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult Males and Females ages 18 and older who are patients at the Dayton VAMC Dermatology clinics
• Skin type must be "Fair", Fitzpatrick type I or II, due to the presence of actinic damage in this population.
• Subjects must have a VA physician's order to receive PDT treatment on their forearms.
• Willing to participate and understand the informed consent document.
• Willing to avoid excess sun exposure/tanning beds to the area to be treated with PDT.
• Has stable transportation to attend study visits at DVA

Exclusion Criteria:

• Currently taking any tricyclic antidepressants (TCAs)
• Currently taking any selective serotonin reuptake inhibitor (SSRI)
• Has Porphyria
• Large tattoos in areas to be tested
• Pregnancy or nursing
• Taking any oral or topical medications that could interfere with the PDT
• Active rashes in the areas

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imipramine and Control Vehicle on Forearms; 10% imipramine and control vehicle (1.5 ml each) are applied on designated separate dorsal forearm.	Drug: Imipramine; 10% imipramine; Other: Control Vehicle; polyethylene glycol: dimethyl sulfoxide Solution
Experimental: Imipramine and Control Vehicle on Face; 10% imipramine and control vehicle (1.5 ml each) are applied on one side of the face for 1 hour.	Drug: Imipramine; 10% imipramine; Other: Control Vehicle; polyethylene glycol: dimethyl sulfoxide Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Forearm Arm Only): Difference in areas of Candida antigen skin test results with PDT+ imipramine	Size of skin reactions from baseline values will be obtained following PDT + vehicle/imipramine using calipers.	7, 30, 90 days post-PDT treatments
(Forearm Arm Only): Difference in redness of Candida antigen skin test results with PDT+ imipramine	Redness of skin reactions from baseline values will be obtained following PDT + vehicle/imipramine using mexameter device and thermal imaging.	7, 30, 90 days post-PDT treatments
Difference in numbers of precancerous AK skin lesions with PDT and imipramine on the face	Differences in baseline values of AK will be obtained following PDT + vehicle/imipramine by counting and mapping on each side of face/scalp.	6, 12 months post-PDT treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in numbers of precancerous AK skin lesions with PDT and imipramine on the forearms	Differences in baseline values of AK will be obtained following PDT + vehicle/imipramine by counting and mapping each forearm/wrist.	6, 12 months post-PDT treatment
(Forearm Arm Only): Difference in gene profile of skin following treatment with PDT + imipramine	Differences in transcriptome RNA values from baseline will be obtained following PDT + vehicle/impramine by use of tissue RNA-seq with a commercial dermal transcriptomal patch.	7 days post-PDT treatment
Differences in post-PDT redness with PDT + imipramine	Differences in redness following PDT + imipramine vs PDT + vehicle from baseline values will be obtained using a mexameter device and thermal imaging on face/forearms.	10 min, 30 min, 24 hours post-PDT treatments
Differences in post-PDT pain with PDT + imipramine	Differences in pain following PDT + imipramine vs PDT + vehicle from baseline values will be obtained using a visual analog scale on face/forearms.	10 min, 30 min, 24 hours post-PDT treatments

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Jeffrey Travers, MD, Dayton VA Medical Center, Dayton, OH

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): January 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Skin Diseases; Precancerous Conditions; Keratosis; Skin and Connective Tissue Diseases; Keratosis, Actinic; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Imipramine
• Other Study ID Numbers: ONCE-001-24S; IRB-2024-639 (Other Identifier: Wright State University IRB); IRB-2024-674 (Other Identifier: Wright State University IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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