Reduced Side-Effects Of Photodynamic Therapy For The Treatment Of Moderate To Severe Acne (i-PDT)

Study Overview
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Brief Summary
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This research study aims to compare different methods for helping difficult to treat or scarring (cystic) acne, ALA-PDT and i-PDT. There is an investigational procedure called photodynamic therapy (ALA-PDT) that has been reported to be very efficient for acne treatment since 2000. Photodynamic therapy (PDT) uses a drug called ALA (aminolevulinic acid), which is marketed as Levulan®. Levulan® is applied directly to facial/back acne. This is the way that it is usually applied. Levulan® is left on the skin for three hours so the skin can absorb it. Next, the skin where the Levulan® was applied is exposed to a red light for activation. The sebaceous glands get obstructed and inflamed causing acne. ALA gets down under your skin through the skin pores to where the glands are. PDT destroys the glands reducing the acne lesion. Levulan® is absorbed by normal skin surrounding the oil glands. Therefore, this procedure also has some side effects. Some of the side effects include pain, burning sensation during the procedure, and redness, tenderness, and swelling after the procedure. At Massachusetts General Hospital's Wellman Center for Photomedicine, the investigators developed another procedure called inhibitory-PDT (i-PDT) that is similar to ALA-PDT. i-PDT is aimed at reducing the side-effects of ALA- PDT. The difference between these two procedures is that i-PDT uses a light source that will prevent Levulan® accumulation in the normal skin surface. The investigators would like to find out if Levulan® will be placed only inside the sebaceous glands.

Detailed Description
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This is a pilot study to compare efficacy and side effects i-PDT and ALA-PDT. All subjects will receive ALA-PDT and i-PDT. Face or back regions will be divided into two sides, the right and left. One half of the face or back will receive ALA-PDT and the other half will receive i-PDT. For subjects with back acne, red light and blue light alone will be applied for comparison. Healthy subjects with difficult to treat moderate or severe acne on the face or back are eligible to enroll. The investigators will enroll about 35 patients at Massachusetts General Hospital (MGH) with follow-ups 1, 3 and 6 months after treatment.

Official Title
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A Pilot Clinical Trial To Reduce Side-Effects Of Photodynamic Therapy For The Treatment Of Moderate To Severe Acne

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: 20 % Aminolevulinic Acid
* Device: Red light only
* Device: Blue light only


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subjects with ages between 14 and 50 years, male or female. Subjects with severe acne lesions (one or more nodules or cysts present) on their backs or face Presence of moderate acne on the back and/or face that has been recalcitrant to previous treatments. Recalcitrant acne is acne with no or mild/temporary (less than 3 months) improvement after using: Accutane® for at least one completed treatment cycle, and/or Oral antibiotic for ≥ 3 months; and/or Topical prescription retinoids (tretinoin - retinoic acid, adapalene, tazarotene or other derivatives) for ≥ 3 months, and/or Topical benzoyl peroxide 2.5% or higher concentrations for ≥ 3 months Hormonal treatments** for ≥ 3 months. Willingness to participate in the study Willingness to receive ALA-PDT treatment Informed consent agreement signed by the subject Willingness to follow the treatment schedule and post treatment care requirements Willingness to not use topical or systemic (oral) anti-acne medications including medicated shampoo or soap during the study period. Exclusion criteria Subjects receiving concurrent oral retinoids or antibiotics ** Subjects with chronic use of antibiotics may be included if proven that its use has not changed the severity of their acne. AND *** Chronic use of antibiotic is considered ≥ 2 years of continuous use. Scarring or infection of the area to be treated Known photosensitivity Presence of suntan in the area to be treated Subjects who have taken medication known to induce photosensitivity in the previous 3 months Subjects who have had prior oral retinoid (Accutane®) use within 6 months of entering the study Prior oral antibiotic use within 1 month of entering the study (see exclusion #1) Topical antibiotic or other topical anti-acne treatments use within 2 weeks of entering the study Known anticoagulation or thromboembolic condition Subjects who are immunosuppressed Subject is unable to comply with treatment, home care or follow-up visits Subject is pregnant or breast feeding Subject has a history of being on photosensitive medications (thiazides [used to treat high blood pressure], tetracyclines, fluoroquinolones griseofulvin or sulfonamides [used to treat infections], sulfonylureas [used to treat diabetes], calcium channel blockers [used to treat hypertension]. phenothiazines [used to treat serious emotional problems]). Known skin sensitivity to blue light Porphyria (a disorder of the metabolism that can lead to sensitivity to light) Allergies to chemicals called porphyrins Subjects who started hormonal treatment (for medical conditions or birth control) within less than 3 months.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No drug, no treatment | |
| Active Comparator: ALA-PDT<br>Drug- topical 20% Aminolevulinic acid - ALA followed by red light irradiation - conventional photodynamic therapy -PDT | Drug: 20 % Aminolevulinic Acid<br>* topical medication for ALA-PDT and i-PDT<br>* Other names: 5-Aminulevulinic acid HCl (ALA): Levulan® Kerastic® (Dusa Pharmaceuticals, Inc, Wilmington, MA, USA) (Dusa Pharmaceuticals);|
| Experimental: i-PDT<br>Drug - topical 20% Aminolevulinic acid - followed by inhibitory light during incubation time, then red light for photodynamic therapy | Drug: 20 % Aminolevulinic Acid<br>* topical medication for ALA-PDT and i-PDT<br>* Other names: 5-Aminulevulinic acid HCl (ALA): Levulan® Kerastic® (Dusa Pharmaceuticals, Inc, Wilmington, MA, USA) (Dusa Pharmaceuticals);Device: Blue light only<br>* Blue light only<br>* Other names: 415 nm LED (Phototherapeutics, Cheshire, UK);|
| Active Comparator: Red Light only<br>Red light only - no drug | Device: Red light only<br>* Red Light therapy<br>* Other names: 635 nm - LED (Phototherapeutics, Cheshire, UK);|
| Active Comparator: Blue light only<br>Blue light only - no drug | Device: Blue light only<br>* Blue light only<br>* Other names: 415 nm LED (Phototherapeutics, Cheshire, UK);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Investigator Global Assessment (IGA) scale for acne vulgaris | 0. Clear: No lesions but erythema and residual hyperpigmentation may be present Almost Clear: few scattered comedones and a few (< five) small papules Mild:< 50% face involved, many comedones/papules and pustules Moderate:> 50% of face involved. Numerous comedones, papules and pustules Severe: Entire face is covered with comedones, numerous papules and pustules and a few nodules and cysts. 1) Clear or almost clear (Grades 0 or 1) as success at 12 weeks. 2) Two grade improvement as success at 12 weeks. | 0, 4, 8, 12, 16, 24 and 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain reduction | Visual Pain Scale - 0 (no pain) -10 (severe pain) | During, immediately after and 24 h after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acne vulgaris, Photodynamic Therapy, Side-effects, Pain