Laser Assisted Delivery of Minoxidil in Androgenetic Alopecia

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and efficacy of fractionated ablative 10,600nm CO2 laser assisted delivery of 2% minoxidil solution in the treatment of MPHL. In this cohort study, patients will randomly be assigned stand-alone laser treatment, laser assisted drug delivery of minoxidil 2% solution, and laser assisted drug delivery of minoxidil 2% solution plus at home 5% minoxidil treatment. The primary endpoints will be to assess the change from baseline in investigator and subject Hair Growth Assessments (HGA), Hair Growth Index (HGI) and the Hair Growth Satisfaction Scale (HGSS) over 8-12 weeks in each of the three groups. The secondary endpoints will be expert assessment of hair density from baseline and evaluation of safety and adverse events, and pharmacokinetic (PK) data.

Detailed Description
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Male pattern hair loss (MPHL) is a common, frustrating, and difficult to manage scalp disease with few treatment options available. Though the mechanism remains unclear, minoxidil is a well-established treatment for MPHL. With the advent of laser assisted drug delivery, the investigators seek to investigate the use of laser assisted minoxidil delivery to improve bioavailability, and subsequent hair growth for subjects MPHL. With an improved clinical outcome and increased treatment efficiency, patient quality of life would be enhanced and fewer at home topical treatments with minoxidil may be required. Additionally, this study will assist in understanding the effects of stand-alone laser therapy on hair growth and may also be used as a background or framework for a growing number of studies investigating this technology as a drug delivery system. MPHL, also known as androgenetic alopecia, is a non-scarring alopecia resulting in gradual hair loss localized to the scalp. In men, this progressive hair loss disorder results in characteristic thinning of hair over the vertex and frontal regions.1 The Hamilton-Norwood scale categorizes this typical clinical progression.2 While the pathogenesis of MPHL is not entirely elucidated, it has been proposed to be an age and hormone dependent process with dihydrotestosterone playing a significant role.2,3 Genetic factors may also contribute to the disease.4 Topical minoxidil is an FDA approved treatment for MPHL. Minoxidil 2 and 5% solution are known to increase hair regrowth in men with androgenetic alopecia.7 While the mechanism remains unknown, it has been proposed minoxidil increases the duration of anagen and vascular supply to the follicular structure.8 Topical treatments for MPHL such as minoxidil have limited efficacy, as topical delivery of medication has low bioavailability.9 With the advent of fractionated ablative and non-ablative laser technologies, more efficient drug delivery to the level of the superficial epidermis and dermis is now possible. The outermost layer of skin, the stratum corneum, impedes the diffusion of topical medications to follicular structures in the dermis and hypodermis. 9 Ablative fractionated laser devices create vertical channels, permitting topical medication to breach the skin's top layer, the stratum corneum, and reach deep skin layers where hair follicles reside.9 Both ablative and non-ablative fractionated laser treatments augment collagen deposition and cause growth factor mediated changes to skin ultrastructure.10 Non-ablative fractionated laser therapy in MPHL patients improves hair density with and without topical administration of growth factor.10 Our proposed study confers an additional mode of treatment beyond laser-only therapy by using an ablative fractionated laser to deliver minoxidil 2% solution percutaneously. Herein, the investigators seek to further optimize patient treatment by investigating a combination of these treatment modalities for management of MPHL. The investigators hypothesize that fractionated ablative 10,600nm CO2 laser treatment and laser assisted drug delivery of minoxidil 2% solution will result in increased hair growth. With this improved clinical outcome and increased treatment efficiency, patient quality of life will be enhanced and fewer at home topical treatments may be required.

Official Title
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The Safety and Efficacy of Fractional Ablative 10, 600nm CO2 Laser-assisted Treatments for Male Pattern Hair Loss: a Randomized Cohort Study Comparing Stand-alone Laser Treatment, Laser Assisted Drug Delivery of Minoxidil 2% Solution , and Laser Assisted Drug Delivery of Minoxidil 2% Solution Plus Self-administration of Minoxidil 5% at Home.

Conditions
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Male Pattern Hair Loss, Androgenetic Alopecia, Male Pattern Baldness

Intervention / Treatment
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* Drug: Post-Laser Minoxidil 2%
* Drug: At-Home Minoxidil 5%
* Device: Laser
* Drug: Post-laser 5mg minoxidil
* Drug: Post-laser 10mg minoxidil
* Drug: Post-laser 20mg minoxidil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males ages 21-65 years old with MPHL Norwood III vertex-V. The vertex scalp must be involved MPHL diagnosed by a board-certified dermatologist Willing to abstain from use of over the counter products and prescription products other than those supplied in the study Willing to abstain from the use of non-steroidal anti-inflammatory medications, aspirin, St. Johns Wart, and high doses of Vitamin E supplementation Subjects must be capable of giving informed consent Willing to adhere to protocol, including scalp examinations and photography Exclusion Criteria: Allergy or intolerance to minoxidil Underlying disease that might be adversely affected by minoxidil. Immunosuppressed patients (history of transplantation, cancer, chemotherapy, splenectomy, HIV) Application of topical immunomodulatory or immunosuppressive agent in the preceding 6 weeks Systemic administration of corticosteroid or other systemic treatment (e.g. prednisone) that has immunomodulatory or other immunosuppressive mechanism of action, in the preceding 8 weeks or planned usage at any time throughout the study Clinical evidence of secondary skin infection (e.g. folliculitis) Other inflammatory or infectious skin disease that might interfere with evaluations during the study Investigational medications within the past 30 days Severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies Oral retinoids within the past 6 months and topical retinoid usage within the past 4 weeks Patients with history of or susceptible to keloid formation Finasteride or dutasteride within the past 6 weeks Spironolactone within the past 6 weeks Active infection Lesions in the treated area suspicious for malignancy Known allergy to hair dye or hair dye components Relevant history of hypotension Hypertension that is untreated or uncontrolled Radiation or chemotherapy to the site Use of topical or oral ketoconazole in the past 6 weeks Hair transplants or weaves Other concomitant types of history of hair loss such as telogen effluvium Medical problems including HIV, connective tissue disorder, PCOS, untreated thyroid disease Psychiatric disease that that may increase risks within the trial Current use of tanning beds or any active tanning Use of antihypertensives or vasodilators following a first-time diagnosis of hypertension within the past 6 months Planned upcoming surgeries Tattoo on scalp Use of oral minoxidil within the past 6 months History of orthostatic hypotension Adults lacking capacity to consent Adults who do not speak English. A medical history or clinical evidence of: acute myocardial infarction, angina, cardiac disease, cardiac tamponade, cerebrovascular disease, coronary artery disease, hypotension, orthostatic hypotension, pericardial effusion, peripheral edema, heart failure, pulmonary hypertension, renal disease, renal failure, renal impairment, pregnancy, breast-feeding, children, pheochromocytoma, skin abrasion, and geriatric.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety Group<br>will participate in one visit, receiving laser assisted delivery of minoxidil and PK data. The safety group treatments will follow dose escalation as follows: Safety Participant 1: Post-laser 5mg minoxidil (0.25ml of 20mg/ml sterile solution, applied post-laser procedure) Safety Participant 2: Post-laser 10mg minoxidil (0.5ml of 20mg/ml sterile solution, applied post-laser procedure) Safety Participant 3: Post-laser 20mg minoxidil (1mL of 20mg/mL sterile solution, applied post-laser procedure) | Device: Laser<br>* Fractional ablative, deep mode, 5% fractional coverage<br>Drug: Post-laser 5mg minoxidil<br>* 0.25ml of 20mg/ml sterile solution, applied post-laser procedure<br>* Other names: Rogaine;Drug: Post-laser 10mg minoxidil<br>* 0.5ml of 20mg/ml sterile solution, applied post-laser procedure<br>* Other names: Rogaine;Drug: Post-laser 20mg minoxidil<br>* 1ml of 20mg/ml sterile solution, applied post-laser procedure<br>* Other names: Rogaine;|
| Placebo Comparator: Placebo<br>Laser: Fractional ablative, deep mode, 5% fractional coverage Post-Laser Saline 0.9%: 2ml of sterile saline solution applied post-laser procedure | Device: Laser<br>* Fractional ablative, deep mode, 5% fractional coverage<br>|
| Experimental: Treatment A<br>Laser: Fractional ablative, deep mode, 5% fractional coverage Post-Laser Minoxidil 2%: 2ml of 20mg/ml sterile solution, applied post-laser procedure | Drug: Post-Laser Minoxidil 2%<br>* 2ml of 20mg/ml sterile solution, applied post-laser procedure<br>* Other names: Rogaine;|
| Experimental: Treatment B<br>Laser: Fractional ablative, deep mode, 5% fractional coverage Post-Laser Minoxidil 2%: 2ml of 20mg/ml sterile solution, applied post-laser procedure At-Home Minoxidil 5%: 2ml of 50mg/ml foam q24 h for duration of study | Drug: Post-Laser Minoxidil 2%<br>* 2ml of 20mg/ml sterile solution, applied post-laser procedure<br>* Other names: Rogaine;Drug: At-Home Minoxidil 5%<br>* 2ml of 50mg/ml foam q24 h for duration of study<br>* Other names: Rogaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hair Growth Assessment (HGA) | Scale indicating graded degree of change represented as no change, worse outcome, better outcome. | End of trial (8-16 weeks) | 
| Hair Growth Index (HGI) | Hair growth is compared from baseline by three self-report questions on a health outcome questionnaire | End of trial (8-16 weeks) | 
| Change in Hair Growth Satisfaction Scale (HGSS) | Hair appearance/growth is compared from baseline by five self-report questions that rank satisfaction with hair growth on a scale from -3 (very dissatisfied) to 3 (very satisfied). | Week 0, Week 4(+4), Week 8(+4) | 
| Change in Investigator Global Assessment of Photography | Scale from -3 (significant worsening) to 3 (significant improvement) assessing hair loss/growth | Week 0, end of trial (8-16 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Additional Investigator Global Assessment of Photography | Scale from -3 (significant worsening) to 3 (significant improvement) assessing hair loss/growth | Week 0, end of trial (8-16 weeks) | 
| Change in Scalp Symptom Assessments | Measure 4 criteria, erythema, scaling, pruritis, and burning/stinging, on a scale from 0 (none) to 4 (severe) | Week 0, Week 4(+4), Week 8(+4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Male Pattern Hair Loss, Androgenetic Alopecia, Male Baldness, Bald, Baldness