Topical Imipramine Cream for Photosensitivity

Overseen By Regulatory Specialist

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Wright State Physicians

Must not be taking: Photosensitizers, Anti-inflammatories, Tricyclics

Disqualifiers: Uncontrolled diabetes, Large tattoos, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a cream containing imipramine, an antidepressant, can help people with photosensitivity, which causes abnormal reactions to sunlight. Researchers aim to determine if the cream can reduce skin redness and block tiny particles released in the skin after UVB light exposure. Participants should have self-identified photosensitivity and not be using medications that increase sensitivity to sunlight. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they are known to make your skin more sensitive to sunlight or if they are anti-inflammatory drugs. The trial does not allow participants to use medications like doxycycline, NSAIDs (except low-dose aspirin), steroids, or any form of imipramine.

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

Research has shown that imipramine has been studied for safety in humans, primarily for treating depression. When taken as a pill, it is generally well-tolerated, though some people have experienced side effects like dizziness, dry mouth, and constipation.

This trial is in its early stages and tests the safety of using imipramine as a cream for skin sensitivity to sunlight. While imipramine is usually safe as a pill, using it as a cream for photosensitivity is new and still under investigation.

Currently, no specific data exists on how well the cream is tolerated. In this early phase, researchers are gathering basic safety information and closely monitoring for any side effects or reactions to ensure its safety for skin use. So far, existing studies have not reported any serious issues from the cream. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for photosensitivity focus on avoiding triggers or using sunscreens and protective clothing. Unlike these standard approaches, the investigational 4% imipramine cream offers a novel topical solution by directly addressing the skin's reaction to UVB exposure. Imipramine, typically known as an antidepressant, is being explored for its potential to stabilize skin cells and reduce photosensitivity reactions. Researchers are excited about this treatment because it could offer a proactive way to manage photosensitivity, potentially reducing the need for lifestyle changes and improving the quality of life for those affected.

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

Research shows that imipramine cream might help reduce skin reactions from UVB light, such as redness and the release of tiny bits of cell material. Some studies suggest that imipramine can alter how skin cells respond to sunlight by reducing certain cellular changes. Although typically known as an antidepressant, imipramine's potential to modify skin reactions to UVB light is under investigation. In this trial, participants will receive 4% imipramine cream applied to UVB-treated areas to evaluate its effectiveness. While the cream's ability to prevent these reactions is still being researched, the aim is to assist people with photosensitivity, who experience unusual reactions to sunlight. ^{3 4 6 7 8}

Who Is on the Research Team?

Jeffrey B Travers, MD, PhD

Principal Investigator

Wright State University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 with photosensitivity, who can provide their medical history and aren't using medications that increase sensitivity to light. Pregnant or nursing women, recent tanning bed users, those on certain antidepressants or anti-inflammatories, and individuals with abnormal scarring or diseases affecting wound healing are excluded.

Inclusion Criteria

Must be able to give informed consent

I can provide my medical history and current medications, and I'm not on any photosensitizing drugs.

People with all skin types are eligible to participate.

Exclusion Criteria

You have a history of unusual scarring, such as keloids.

I am currently taking a tricyclic antidepressant.

I do not have conditions like uncontrolled diabetes that could affect wound healing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive UVB treatment and topical imipramine application to assess microvesicle particle release and erythema reactions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in microvesicle particle levels and skin erythema after treatment

24 hours

What Are the Treatments Tested in This Trial?

Interventions

• Imipramine

Trial Overview The study tests if a cream containing 4% Imipramine can prevent skin reactions like redness and microvesicle particle release after exposure to UVB light in people sensitive to sunlight. Participants will apply the cream before UVB treatment on a small skin area.

How Is the Trial Designed?

Group I: 4% Imipramine Cream on UVB-Treated Areas Experimental Treatment 2 Interventions

* 2g of 4% imipramine cream will be applied to the UVB-treated areas on volar forearm and back. * 2g of base cream will be applied to the UVB-treated areas on volar forearm and back. * No cream will be applied to a UVB-treated area on the back

Imipramine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tofranil for:

• Depression
• Bedwetting (Nocturnal Enuresis)
• Painful Diabetic Neuropathy†
• Social Phobia (Social Anxiety Disorder)†
• Panic Disorder†
• Stress and Urge Urinary Incontinence† (Non-neurogenic Overactive Bladder)†

Approved in European Union as Imipramine for:

• Depression
• Nocturnal Enuresis

Approved in Canada as Imipramine for:

• Depression
• Nocturnal Enuresis

Who Is Running the Clinical Trial?

Wright State Physicians

Lead Sponsor

Trials

4

Recruited

100+

Wright State University

Lead Sponsor

Trials

47

Recruited

55,300+

Published Research Related to This Trial

In a study of 40 patients with depressive illness, both single-dose imipramine pamoate and divided-dose imipramine hydrochloride were found to be highly effective antidepressants, confirming their therapeutic equivalence.

Both treatments had similar mild side effects, with no significant adverse effects on blood, kidney, or liver functions, indicating a good safety profile for both forms of imipramine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled double blind comparative study of single dose administration of imipramine pamoate and divided dose of imipramine hydrochloride in depressive illness. Khorana, AB.[2013]

Imipramine, a tricyclic antidepressant, shows a dose-dependent ability to reduce pain in mice, with effective doses (ED50) around 20-27.5 nmol, indicating its potential as a pain relief option.

The antinociceptive effects of imipramine do not rely on common pain pathways involving alpha-adrenergic, serotonergic, or opioid receptors, suggesting a unique mechanism of action that may involve blocking substance P receptors in the spinal cord.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipramine inhibits intrathecal substance P-induced behavior and blocks spinal cord substance P receptors in mice. Iwashita, T., Shimizu, T.[2019]

In a 4-week study involving 17 centers and comparing 300-600 mg/d of moclobemide to 100-200 mg/d of imipramine in patients with Major Depressive Episode, both medications showed similar efficacy in reducing depression symptoms, with a mean reduction of 51.7% for moclobemide and 52.1% for imipramine.

Moclobemide demonstrated better tolerability, with 83% of patients reporting good or very good tolerability compared to 74% for imipramine, and fewer adverse events (56% for moclobemide vs. 69% for imipramine), indicating it may be a safer alternative for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of moclobemide compared with imipramine in the treatment of major depressive disorder. Double-blind multicenter study, Austria. Hebenstreit, GF., Loidl, M., Baumhackl, U., et al.[2019]

Amitriptyline, a tricyclic antidepressant, can cause various skin reactions, including rashes and hypersensitivity reactions, which are among the most common side effects of psychotropic drugs.

The case of a 24-year-old woman illustrates that hypersensitivity syndrome can occur three weeks after starting amitriptyline, leading to serious skin and systemic symptoms, but these typically resolve after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity syndrome caused by amitriptyline administration. Milionis, HJ., Skopelitou, A., Elisaf, MS.[2019]

Maprotiline is a new type of antidepressant that shows potent effects similar to traditional antidepressants like amitriptyline and imipramine, particularly in inhibiting certain behavioral responses in animal models.

It has a lower toxicity profile compared to amitriptyline and imipramine, with an LD50 approximately twice that of imipramine, indicating a safer therapeutic window.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Behavior pharmacology of maprotiline, a new antidepressant]. Ueki, S., Fujiwara, M., Inoue, K., et al.[2019]

Classical antidepressants like imipramine and amitriptyline, as well as the atypical antidepressant iprindole, produce a sustained reduction in pain perception in mice, which is sensitive to the opiate antagonist naloxone, indicating an involvement of opioid pathways in their pain-relieving effects.

The study suggests that the pain-relieving effects of these antidepressants may also involve serotonin receptors, as blocking these receptors with methysergide eliminated the antidepressants' ability to change pain thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoalgesia induced by antidepressants in mice: a case for opioids and serotonin. de Felipe, MC., de Ceballos, ML., Fuentes, JA.[2019]

In a four-week double-blind trial involving 341 patients, maprotiline and imipramine both significantly reduced depression symptoms, showing similar efficacy based on various assessment scales.

Maprotiline was associated with fewer treatment-emergent side effects, particularly nausea, nervousness, and increased sweating, suggesting it may be better tolerated than imipramine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of maprotiline with imipramine in severe depression: a multicenter controlled trial. Logue, JN., Sachais, BA., Feighner, JP.[2019]

In a study of 557 outpatients treated with imipramine, 75% of patients were treated for depression, and the medication showed a 65% efficacy rate at a typical dose of 75 mg per day, suggesting that optimal dosing may relate to the severity of mood disorders.

Imipramine was also effective for post-contusional syndrome, particularly when treatment was initiated early and without loss of consciousness, as well as for phobic symptoms and functional headaches, indicating its potential use in cases where depression may be masked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Imipramine and neuro-psychiatry. Retrospective study of 557 out-patients treated in a neuro-psychiatric unit (author's transl)]. Brion, S., Boulenger, JP.[2015]

In a four-week study involving neurotic depressives, maprotiline demonstrated slightly greater effectiveness than imipramine on various depression rating scales, indicating its potential as a strong antidepressant.

Maprotiline also showed a faster onset of action and fewer anticholinergic side effects compared to imipramine, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maprotiline versus imipramine and placebo in neurotic depression. van der Velde, CD.[2013]

Imipramine, at a dose of 15 mg/kg, effectively reduced immobility in the forced swimming test in mice, indicating its anti-immobility or antidepressant-like effect, which was influenced by various receptor antagonists.

The study suggests that the 5-HT1C receptors play a significant role in the mechanism of action of imipramine, as evidenced by its ability to inhibit binding to these receptors, while other receptor antagonists did not affect imipramine's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence that imipramine activates 5-HT1C receptor function. Borsini, F., Cesana, R., Vidi, A., et al.[2019]

Maprotiline hydrochloride was evaluated for its antidepressant effects in a multicenter study involving 134 patients aged 17 to 83 with dysthymic or major depressive disorders.

The study primarily used a starting dosage of 75 mg/day, with a mean dosage of 71.6 mg/day, indicating a standardized approach to treatment among participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of depression with maprotiline hydrochloride: multicenter evaluation of efficacy and tolerability. [2013]

In a study of 72 depressed outpatients, both moclobemide and imipramine were found to be significantly more effective than placebo in reducing depressive symptoms over 6 weeks, with moclobemide showing a slightly faster response.

Moclobemide was well tolerated in the long term, maintaining its efficacy over a 52-week follow-up, suggesting it could be a viable option for ongoing treatment of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind comparison of moclobemide, imipramine and placebo in depressive patients. Ucha Udabe, R., Márquez, CA., Traballi, CA., et al.[2019]

In a study of 57 neurotically depressed outpatients, both imipramine pamoate and amitriptyline were found to be equally effective in treating neurotic depression over a four-week period.

Patients taking imipramine pamoate experienced significantly earlier rising times and a trend towards better sleep quality, while side effects were similar for both medications, though more patients reported side effects with amitriptyline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline? Goldberg, HL., Finnerty, RJ.[2015]

Citations

1. withpower.com withpower.com/trial/phase-1-7-2021-68f70

Topical Imipramine Cream for Photosensitivity Trial Overview The study tests if a cream containing 4% Imipramine can prevent skin reactions like redness and microvesicle particle release after exposure to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04520217

Testing Use of Topical Imipramine in Reducing Ultraviolet ... First, researchers will assess whether subjects who have clinically abnormal reactions to sunlight (photosensitivity) have increased levels of microvesicle ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8401619/

Drug-Induced Photosensitivity—From Light and Chemistry to ... Imipramine causes purple/slate-grey/golden-brown/dark brown discoloration of the sun-exposed areas and iris color change. There is a hypothesis that imipramine ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05688904/the-effect-of-topical-imipramine-on-pain-and-effectiveness-of-topical-photodynamic-therapy

The Effect of Topical Imipramine on Pain and ... 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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38433456/

The acid sphingomyelinase inhibitor imipramine enhances the ... The acid sphingomyelinase inhibitor imipramine enhances the release of UV photoproduct-containing DNA in small extracellular vesicles in UVB- ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/imipramine-oral-route/description/drg-20072148

Imipramine (oral route) - Side effects & dosage Imipramine is used to treat depression. It belongs to a group of medicines known as tricyclic antidepressants (TCA).

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/t/Tofraniltab.pdf

Data sheet Hypersensitivity to imipramine and any of the excipients listed in section 6.1, or cross- sensitivity to tricyclic antidepressants of the dibenzazepine group.

8. webmd.com webmd.com/drugs/2/drug-8664/imipramine-oral/details

Imipramine: Uses, Side Effects, Interactions, Pictures, ... Find patient medical information for Imipramine on WebMD including its uses, side effects and safety, interactions, pictures, warnings, ...