Imipramine + Photodynamic Therapy for Actinic Keratosis

Overseen By Regulatory Specialist

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Wright State University

Must not be taking: Tricyclics, SSRIs, others

Disqualifiers: Porphyria, Pregnancy, Active rashes, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is testing the use of topical Imipramine in combination with topical photodynamic therapy's (PDT) effect on pain following treatment. PDT is a commonly used treatment in dermatology for patients who have many pre-cancers (actinic keratosis-AKs) on their skin. These are both FDA-approved treatments, but this study is evaluating their use in combination, which has not been evaluated in the past. 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 participate, the subject and their dermatologist have decided that they would benefit from PDT to treat their skin due to many AK precancerous lesions. Please note that neither PDT nor imipramine are experimental treatments, but treating their skin with imipramine before PDT is a new approach.

Will I have to stop taking my current medications?

Yes, if you are currently taking any tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), you will need to stop. Also, if you are taking any oral or topical medications that could interfere with the photodynamic therapy, you will need to stop those as well.

How does the treatment Imipramine + Photodynamic Therapy differ from other treatments for actinic keratosis?

The combination of Imipramine with Photodynamic Therapy (PDT) for actinic keratosis is unique because it potentially introduces a novel mechanism of action by combining a drug typically used for depression with a light-activated treatment. This approach may offer a new way to enhance the effectiveness of PDT, which is already known for being a safe and effective method with minimal side effects compared to other treatments like cryotherapy and topical medications. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Imipramine + Photodynamic Therapy for Actinic Keratosis?

Photodynamic therapy (PDT) is shown to be an effective and safe treatment for actinic keratosis, especially on the face and scalp, with minimal side effects. While Imipramine is not directly mentioned in the context of actinic keratosis, PDT itself is well-supported by research as a beneficial treatment for this condition. ^{1 3 5 6 7}

Who Is on the Research Team?

Craig Rohan, MD

Principal Investigator

Wright State University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with fair skin (Fitzpatrick type I to III) who have many pre-cancerous lesions called actinic keratosis and are prescribed photodynamic therapy (PDT) for their face, scalp, or forearms. Participants must avoid excess sun exposure and tanning beds. Excluded are those with porphyria, on certain antidepressants or SSRIs, pregnant or nursing women, people with active rashes or large tattoos in the area, and anyone taking medications that interfere with PDT.

Inclusion Criteria

I have a doctor's order for PDT treatment on my face, scalp, or forearms.

I have fair skin, prone to sunburns, Fitzpatrick type I to III.

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

Exclusion Criteria

I have porphyria.

I am currently taking tricyclic antidepressants.

I am currently taking an SSRI medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical Imipramine followed by photodynamic therapy (PDT) to treat actinic keratosis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in itch and pain levels, and the number of precancerous actinic keratosis lesions

6 months

Periodic assessments

What Are the Treatments Tested in This Trial?

Interventions

• Imipramine

Trial Overview The study tests topical Imipramine applied before PDT to see if it reduces pain from the treatment and improves its effectiveness against actinic keratosis. Both treatments are FDA-approved separately; this trial examines their combined use which hasn't been studied before.

How Is the Trial Designed?

Group I: Imipramine Active Control 1 Intervention

Topical 4% Imipramine

Group II: Vehicle Placebo Group 1 Intervention

Vehicle

Who Is Running the Clinical Trial?

Wright State University

Lead Sponsor

Trials

47

Recruited

55,300+

Published Research Related to This Trial

In a study involving 31 patients, the new treatment method of Intense Pulsed Light-Photodynamic Therapy (IPL-PDT) achieved a remarkable 95% complete clearance rate for actinic keratosis, demonstrating its high efficacy.

IPL-PDT is shown to be a safe and well-tolerated alternative to conventional treatments for actinic keratosis, with minimal side effects and a preference for its versatility and speed of application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy activated by intense pulsed light in the treatment of actinic keratosis. Michelini, M.[2021]

Topical 5-fluorouracil (5-FU) at 5% concentration is considered the most effective treatment for actinic keratosis (AK), although lower concentrations may also be effective, highlighting the need for personalized treatment based on patient factors.

Photodynamic light therapy is more effective than daylight phototherapy for treating AKs, despite being more painful, while other treatments like topical diclofenac are less effective than 5-FU and imiquimod.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review. Arcuri, D., Ramchatesingh, B., Lagacé, F., et al.[2023]

Topical 5-aminolaevulinic acid photodynamic therapy (5-ALA PDT) was effective in treating extensive scalp actinic keratoses (AKs) in four patients, with three achieving complete clearance and one showing significant improvement.

The treatment resulted in a remission period lasting up to 6 months, suggesting that 5-ALA PDT could be a promising alternative for patients with widespread AKs, especially when traditional methods like cryotherapy and 5-fluorouracil are insufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratoses. Markham, T., Collins, P.[2019]

Experts reached a consensus that lesion-directed treatments are best for patients with few actinic keratosis (AK) lesions, while those with multiple AKs require personalized therapy, often needing more than one treatment for effective clearance.

Methyl aminolevulinate photodynamic therapy (PDT), daylight PDT, and imiquimod cream showed the lowest rates of new AKs after treatment, and regular sunscreen use, along with oral nicotinamide, can help prevent new squamous cell carcinomas in patients with AKs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian expert consensus paper on the management of patients with actinic keratoses. Moscarella, E., Di Brizzi, EV., Casari, A., et al.[2021]

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is an effective and safe treatment for nonhypertrophic actinic keratosis (AK) lesions on the scalp and face, with a practical 1-hour incubation time.

Compared to other treatments like 5-fluorouracil (5-FU) and imiquimod, ALA PDT has shown efficacy against multiple AKs while having fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatments of actinic keratosis. Gold, MH., Nestor, MS.[2022]

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs), which can progress to squamous cell carcinoma if untreated, highlighting its importance in dermatological care.

The article provides practical guidance on PDT procedures and discusses outcomes from clinical trials, particularly emphasizing its use in high-risk groups like transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy for actinic keratoses. Kalisiak, MS., Rao, J.[2016]

In a pilot study involving 5 male subjects with actinic keratosis, daylight-mediated photodynamic therapy (DL-PDT) using 16% methyl aminolevulinate (MAL) cream showed an 80% complete response rate at 3 months, compared to 93% for topical 5-fluorouracil (5-FU).

DL-PDT resulted in fewer treatment-related adverse events and quicker recovery times than 5-FU, making it a preferred option for patients seeking effective treatment for actinic keratosis with minimal disruption to their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daylight Photodynamic Therapy Versus 5-Fluorouracil for the Treatment of Actinic Keratosis: A Case Series. Galimberti, GN.[2022]

Citations

1. Italy pubmed.ncbi.nlm.nih.gov

Photodynamic therapy activated by intense pulsed light in the treatment of actinic keratosis. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratoses. [2019]

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

Italian expert consensus paper on the management of patients with actinic keratoses. [2021]

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

Current treatments of actinic keratosis. [2022]

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

Photodynamic therapy for actinic keratoses. [2016]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Daylight Photodynamic Therapy Versus 5-Fluorouracil for the Treatment of Actinic Keratosis: A Case Series. [2022]