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

Trial Summary

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).

What data supports the effectiveness of the drug Imipramine for treating actinic keratosis?

There is no direct evidence supporting the effectiveness of Imipramine for actinic keratosis, but antidepressants, including tricyclic ones like Imipramine, have shown anti-inflammatory effects in dermatological conditions, which might suggest potential benefits. ^{1 2 3 4 5}

Is topical imipramine safe for use in humans?

Imipramine, a tricyclic antidepressant, has been associated with rare cases of skin discoloration (hyperpigmentation) and potential phototoxicity (skin reaction to sunlight) when taken orally. These side effects suggest caution may be needed when considering its use on the skin. ^{4 5 6 7 8}

How does the drug Imipramine differ from other treatments for actinic keratosis?

Topical Imipramine is unique for actinic keratosis as it is traditionally a tricyclic antidepressant used for mood disorders, and its use in dermatology is not common. Unlike standard treatments for actinic keratosis, which often involve direct removal or destruction of lesions, Imipramine's potential dermatological effects may be related to its histamine-blocking properties, which are beneficial in other skin conditions. ^{4 5 6 9 10}

What is the purpose of this trial?

The purpose of this study is to test the use of topical imipramine in combination with topical photodynamic therapy's (PDT) effect on 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.

Research Team

Jeffrey Travers, MD

Principal Investigator

Dayton VA Medical Center, Dayton, OH

Eligibility Criteria

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

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

Has stable transportation to attend study visits at DVA

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

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

Treatment Details

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.

Participant Groups

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+

References

1. Canada pubmed.ncbi.nlm.nih.gov

Antidepressant drugs in dermatology. [2004]

2. Sweden pubmed.ncbi.nlm.nih.gov

Antidepressants have Anti-inflammatory Effects that may be Relevant to Dermatology: A Systematic Review. [2022]

3. Sweden pubmed.ncbi.nlm.nih.gov

Increased antidepressant drug exposure in psoriasis patients: a longitudinal population-based cohort study. [2013]

4. England pubmed.ncbi.nlm.nih.gov

The use of antidepressant drugs in dermatology. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Imipramine-induced hyperpigmentation. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Imipramine-associated hyperpigmentation. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Immune-Regulatory and Molecular Effects of Antidepressants on the Inflamed Human Keratinocyte HaCaT Cell Line. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

An approach to evaluate metabolite-related phototoxicity with combined use of photochemical properties and skin deposition. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Novel hyperpigmentation pathophysiology following a prolonged course of imipramine therapy. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A shea butter-based ketamine ointment: The antidepressant effects of transdermal ketamine in rats. [2023]