Role of Reverse Transcriptase Inhibitors in the Treatment of Psoriasis

Study Overview
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Brief Summary
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The investigators hypothesize that the inhibition of endogenous reverse transcriptase would: (1) reduce excess cytosolic DNA, stress initiating the inflammatory loop at the origin of psoriatic lesions, and (2) interrupt the loop and lighten lesions

Official Title
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Role of Reverse Transcriptase Inhibitors in the Treatment of Psoriasis: A Proof of Biological Concept Test

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Generic antiretroviral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient suffering from plaque psoriasis for more than a year with at least one active skin lesion> 4 cm2 in the photo-protected area. Patient using effective contraception (IUD, adapted pill, condom, etc.) The patient must have given their free and informed consent and signed the consent form The patient must be a member or beneficiary of a health insurance plan Exclusion Criteria: Patient with another form or stage of psoriasis Patient on anti-cytokine treatment during the 6 months (180 days) before inclusion Patient under systemic treatment based on (1) corticosteroids, (2) antibiotics, (3) methotrexate, ciclosporin, soriatane, hydroxyurea, apremilast or (4) PUVA, (5) UVB, (6) vitamin D3 during the 4 weeks (28 days) before inclusion Patient on topical corticosteroid or retinoid treatment during the 2 weeks (15 days) before inclusion Patient with renal insufficiency; taking nephrotoxic agents (aminoglycosides, multiple or high doses of NSAIDs, etc.); creatinine clearance less than 50 ml / min; serum phosphorus below 1.0 mg / dl (0.32 mmol / l). Patient with active viral infection (HBV, HCV and HIV), or uncontrolled acute infection. Patient with hypersensitivity to one of the active substances or to any of the excipients (non-medicinal ingredients). Patient with uncontrolled coagulation disorder, history of keloid scars Patient with an allergy to local anesthetics; any condition likely to interfere at the time of the pre-inclusion visit, with the evaluation of the main objective such as eczema, psychiatric disorders Patient with uncontrolled systemic parameters The subject is participating in an interventional study, or is in a period of exclusion determined by a previous study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psoriasis patients<br> | Drug: Generic antiretroviral<br>* 200mg emtricitabine plus 245mg tenofovir diisopropyl fumarate for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients no longer presenting S9.6:D5H6 RNA:DNA duplex | Biopsy screening for S9.6:D5H6 RNA:DNA duplex by immunofluorescence | Day 0 | 
| Percentage of patients no longer presenting S9.6:D5H6 RNA:DNA duplex | Biopsy screening for S9.6:D5H6 RNA:DNA duplex by immunofluorescence | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in endogenous reverse transcriptase | µUI/mL reverse transcriptase activity tested in serum assayed using CAVIDI HS Mg-RT kit | Day 0 | 
| Percentage change in endogenous reverse transcriptase | µUI/mL reverse transcriptase activity tested in serum assayed using CAVIDI HS Mg-RT kit | Day 7 | 
| Percentage change in Ki67 proliferation marker expression | Percentage of cells positive for Ki67 marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in Ki67 proliferation marker expression | Percentage of cells positive for Ki67 marker on cutaneous immunohistochemistry | Day 7 | 
| Percentage change in CK10 differentiation marker expression | Percentage of cells positive for CK10 marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in CK10 differentiation marker expression | Percentage of cells positive for CK10 marker on cutaneous immunohistochemistry | Day 7 | 
| Percentage change in filaggrin differentiation marker expression | Percentage of cells positive for filaggrin marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in filaggrin differentiation marker expression | Percentage of cells positive for filaggrin marker on cutaneous immunohistochemistry | Day 7 | 
| Percentage change in CD4 inflammation marker expression | Percentage of cells positive for CD4 marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in CD4 inflammation marker expression | Percentage of cells positive for CD4 marker on cutaneous immunohistochemistry | Day 7 | 
| Percentage change in CD8 inflammation marker expression | Percentage of cells positive for CD8 marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in CD8 inflammation marker expression | Percentage of cells positive for CD8 marker on cutaneous immunohistochemistry | Day 7 | 
| Percentage change in CD11c inflammation marker expression | Percentage of cells positive for CD11c marker on cutaneous immunohistochemistry | Day 0 | 
| Percentage change in CD11c inflammation marker expression | Percentage of cells positive for CD11c marker on cutaneous immunohistochemistry | Day 7 | 
| Average percentage change of Psoriasis Area Severity Index | Scale of four variables of psoriasis severity (minimum score 0 maximum score 72) | Day 7 | 
| Number of side effects | Anticipated side effects = diarrhea, vomiting, nausea, dizziness or headache, feeling weak or rash | Day 7 | 
| Number of side effects | Anticipated side effects = diarrhea, vomiting, nausea, dizziness or headache, feeling weak or rash | Day 14 |