Topical Imipramine for Actinic Keratosis

Overseen By Jeffrey Travers, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Tricyclics, SSRIs, others

Disqualifiers: Porphyria, Pregnancy, Rashes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat actinic keratosis (AK), which are rough skin patches that can become cancerous, by combining two treatments. The researchers aim to determine if a cream containing imipramine, typically an antidepressant, can enhance the effectiveness of photodynamic therapy (PDT), a standard skin treatment, by reducing its impact on the immune system. This study targets individuals with numerous AK spots who are already scheduled to receive PDT on their forearms. Participants should have fair skin and be able to visit the study site in Dayton. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

You will need to stop taking any tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) to participate in this trial. Also, you cannot take any oral or topical medications that could interfere with the photodynamic therapy (PDT).

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using imipramine as a skin treatment has been tested for safety and tolerability. In these studies, side effects were manageable, and no major safety issues emerged. Both imipramine and photodynamic therapy (PDT) have FDA approval for other uses, indicating thorough safety evaluations in people. However, this study explores their combined use, which is new.

Previous studies with similar skin treatments for actinic keratosis (AK) have shown few safety problems, suggesting that this treatment might be well-tolerated. Although imipramine is not typically used for AK, it has proven safe in its approved uses. These points may help prospective trial participants feel more informed about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for actinic keratosis?

Unlike the standard treatments for actinic keratosis, which typically involve cryotherapy, topical creams like 5-fluorouracil, or photodynamic therapy, imipramine offers a novel approach. Imipramine is a tricyclic antidepressant, and its use here is unique because it taps into an entirely different mechanism of action, potentially affecting cellular pathways involved in skin lesion development. Researchers are excited about this topical treatment because it could provide a new, non-invasive option that minimizes side effects associated with more aggressive therapies. Plus, applying it directly to the skin might offer a targeted approach, reducing the risk of systemic side effects.

What evidence suggests that this treatment might be an effective treatment for actinic keratosis?

This trial will evaluate the use of topical imipramine for actinic keratosis. Research has shown that combining imipramine with photodynamic therapy (PDT) might enhance the treatment of actinic keratosis (AK). In animal studies, imipramine reduced the immune system suppression caused by PDT, potentially improving the treatment's effectiveness. Another study found that a similar treatment method cleared 95% of AK cases. While imipramine may help reduce treatment pain, its combination with PDT could improve outcomes for those with numerous precancerous skin spots. ^{2 6 7 8 9}

Who Is on the Research Team?

Jeffrey Travers, MD

Principal Investigator

Dayton VA Medical Center, Dayton, OH

Are You a Good Fit for This Trial?

This trial is for US veterans with many pre-cancers on their skin, known as actinic keratosis. Participants must be candidates for photodynamic therapy (PDT) as decided by their provider. The study excludes those who cannot consent to PDT or have conditions that might interfere with the treatment.

Inclusion Criteria

Has stable transportation to attend study visits at DVA

I will avoid too much sun or using tanning beds on the area treated.

Willing to participate and understand the informed consent document

Exclusion Criteria

I am currently taking tricyclic antidepressants.

I am currently taking an SSRI medication.

Large tattoos in areas to be tested

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical imipramine in combination with photodynamic therapy (PDT) to assess its effect on immunosuppression

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of skin reactions, gene profiles, redness, pain, and precancerous lesions

12 months

Multiple visits at 7, 30, 90 days, and 6, 12 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Imipramine

Trial Overview The study tests topical imipramine combined with PDT against a control vehicle (placebo) with PDT to see if it reduces immunosuppression and enhances treatment effectiveness. Only the combination use of imipramine is experimental; PDT alone is standard care.

How Is the Trial Designed?

Group I: Imipramine (right forearm/dorsal wrist) and Control Vehicle (left forearm/dorsal wrist) Experimental Treatment 2 Interventions

10% imipramine and control vehicle (1.5 ml each) are applied on designated separate dorsal forearm.

Group II: Imipramine (left forearm/dorsal wrist) and Control Vehicle (right forearm/dorsal wrist) Experimental Treatment 2 Interventions

10% imipramine and control vehicle (1.5 ml each) are applied on designated separate dorsal forearm.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Citations

1. withpower.com withpower.com/trial/phase-1-keratosis-actinic-2-2023-b7217

Imipramine + Photodynamic Therapy for Actinic Keratosis In a study involving 31 patients, the new treatment method of Intense Pulsed Light-Photodynamic Therapy (IPL-PDT) achieved a remarkable 95% complete clearance ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3013595/

Topical Imiquimod Therapy for Actinic Keratosis However, after 12 months of follow-up, investigator assessments rated the cosmetic outcome as excellent in 81 percent of topical imiquimod-treated subjects, as ...

3. careacross.com careacross.com/clinical-trials/trial/NCT05688904

The Effect of Topical Imipramine on Pain and ... The investigators have been doing studies using animals that suggest that imipramine might make the PDT less painful and might help it work better. In order to ...

4. reporter.nih.gov reporter.nih.gov/search/15EEC10D4C8DC5D37598B8961CAA4A01A2FFCEB861BF/project-details/11051941

Project Details PROJECT SUMMARY Actinic neoplasia (precancerous actinic keratosis ... topical aSMase inhibitor imipramine will increase the effectiveness of this therapy.

5. mdpi.com mdpi.com/2072-6694/16/6/1133

Topical Immunotherapy for Actinic Keratosis and Field ... A network meta-analysis showed that 5-FU 5% followed by 5-FU 4% seemed to be superior in efficacy than other treatments for AK [44]. Additionally, pretreatment ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33834933/

Safety of topical interventions for the treatment of actinic ... This expert review provides a comprehensive and up-to-date overview of the safety considerations of the commonly prescribed topical treatment agents.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2010/022483Orig1s000OtherR.pdf

22483Orig1s000 - accessdata.fda.gov A review of the clinical trial safety database, “Analysis of Adverse Events from 3M Sponsored. Clinical Studies of Topical Imiquimod,” was ...

8. go.drugbank.com go.drugbank.com/conditions/DBCOND0065881

Actinic Keratosis (AK) (DBCOND0065881) Associated Data ; NCT00544297. A Study to Examine the Safety and Toleration of PEP005 Topical Gel in Patients With Actinic Keratoses on the Top of the Hand.

9. jddonline.com jddonline.com/wp-content/themes/jdd-salient-child/download.php?pii=S1545961621Ss4s4X&download=1

Safety and Tolerability of Topical Agents for Actinic Keratosis Conclusions: FDA-approved topical agents for the treatment of multiple AKs have minimal safety concerns.