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?

This trial tests whether imipramine, a topical treatment, can reduce pain and possibly enhance the effectiveness of photodynamic therapy (PDT) for actinic keratosis, a skin condition with precancerous lesions. Both treatments have approval, but their combination is new and untested in humans. Ideal participants have fair skin, numerous actinic keratosis lesions, and have been advised by their dermatologist to undergo PDT on areas like the face, scalp, or forearms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both imipramine and photodynamic therapy (PDT) have already received FDA approval for other uses, which helps reassure about their safety. Imipramine typically serves as an antidepressant, while PDT often treats actinic keratosis, a type of skin pre-cancer.

Although combining these two treatments is new, animal studies suggest that imipramine might reduce pain and enhance PDT's effectiveness. This is a Phase 1 study, focusing primarily on safety. Early stages of clinical trials like this generally ensure a new treatment's safety for people.

Since these treatments already have FDA approval for other uses, they are expected to be well-tolerated. However, because this specific combination is new, participants must report any side effects experienced during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for actinic keratosis, which often include topical creams like 5-fluorouracil and procedures such as cryotherapy, imipramine uses a novel approach by targeting the condition with a topical antidepressant. Researchers are excited because imipramine, traditionally used to treat depression, may offer a unique mechanism of action that could reduce the proliferation of abnormal skin cells. This could potentially make the treatment more effective or faster-acting compared to existing options. Additionally, the combination with photodynamic therapy might enhance its efficacy, providing a promising new avenue for managing actinic keratosis.

What evidence suggests that this trial's treatments could be effective for actinic keratosis?

Research has shown that topical photodynamic therapy (PDT) effectively treats actinic keratosis, a skin condition, with about 74.5% of cases clearing up completely. In this trial, one group will receive PDT combined with imipramine, a medication typically used for depression. Animal studies suggest this combination might reduce pain and enhance effectiveness. Imipramine aims to boost PDT's efficacy. Although this combination is new, current evidence is promising for reducing pain and improving outcomes for actinic keratosis. ^{1 2 6 7 8}

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

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]

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]

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]

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]

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]

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]

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]

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The State of the Art in the Treatment of Actinic Keratosis ...

Real-world studies confirmed similar efficacy, reporting complete clearance in 74.5% of AKs and no recurrences at 6 months in 65% of cases [53].

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Keratosis

Integrated disease information for Keratosis including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 78 data sources.

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Imipramine is a tricyclic antidepressant indicated for the treatment of depression and to reduce childhood enuresis.

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Subject Index

... results on interim 4th-year safety and patient outcomes. AB170 ... Arms and forearms: LEO 43204 safety for actinic keratosis on, first in man trial of.

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Four placebo-controlled randomized controlled trials (RCTs) evaluated the efficacy and safety of 0.5% 5-FU, indicating that the lower concentration of 5-FU is ...