Evaluating the Effect of Solius UV Light Source in Improving Serum Levels of 25-hydroxyvitamin D in Vitamin D Deficient/ Insufficient Adults of Various Skin Types: A Feasibility Study
Phase: NA
Conditions: Vitamin D Deficiency, Vitamin D Insufficiency
Sponsor: Boston University

 
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Evaluating the effect of Solius UV light source in improving 
serum levels of 25-hydroxyvitamin D in vitamin D deficient/ 
insufficient adults of various skin types: A feasibility study 
 
 
ClinicalTrials.gov number: NCT04865432 
Protocol Version Number: 1.3 Revised 6-28-2021 
Funding Mechanism: Provided by SOLIUS company 
Principal Investigator: Dr. Michael F. Holick 
 
Phone: (617) 358-6139 
 
E-mail: mfholick@bu.edu 
Study Coordinator: Kimberly Garcia 
85 E Newton St, M-1013 
Boston, MA 02118 
P: (617) 358-6139 
F: (617) 358-6141 
Email: kgarcia2@bu.edu  
 
Statistical Plan page 19 
 
 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of Boston University School of Medicine. No part of it 
may be transmitted, reproduced, published, or used by other persons without prior written 
authorization from the study sponsor. 
 
 

 
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TABLE OF CONTENTS 
1 List of Abbreviations .............................................................................................................. 3 
2 Protocol Summary .................................................................................................................. 3 
3 Background/Rationale & Purpose ....................................................................................... 4 
3.1 
Background Information .............................................................................................. 4 
3.2 
Rationale and Purpose ................................................................................................ 7 
4 Objectives ................................................................................................................................ 7 
4.1 
Study endpoint .............................................................................................................. 7 
4.1.1 
Endpoint Measures ........................................................................................ 7 
5 Study Design ........................................................................................................................... 8 
6 Potential Risks and Benefits ............................................................................................... 10 
6.1 
Risks ............................................................................................................................. 10 
6.2 
Potential Benefits ........................................................................................................ 11 
6.3 
Analysis of Risks in Relation to Benefits ................................................................. 12 
7 Study Subject Selection ...................................................................................................... 12 
7.1 
Subject Inclusion Criteria ........................................................................................... 12 
7.2 
Subject Exclusion Criteria ......................................................................................... 12 
8 Study Intervention ................................................................................................................ 13 
9 Study Procedures ................................................................................................................. 13 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ................................ 15 
10.1 Definitions .................................................................................................................... 15 
10.2 Safety Review ............................................................................................................. 16 
10.3 Reporting Plans .......................................................................................................... 17 
10.4 Stopping Rules ............................................................................................................ 17 
11 Data Handling and Record Keeping .................................................................................. 17 
11.1 Confidentiality .............................................................................................................. 17 
11.2 Source Documents ..................................................................................................... 18 
11.3 Case Report Forms .................................................................................................... 18 
11.4 Study Records Retention .......................................................................................... 18 
12 Statistical Plan ...................................................................................................................... 19 
12.1 Study Hypotheses ...................................................................................................... 19 
12.2 Sample Size Determination ...................................................................................... 19 
13 Ethics/Protection of Human Subjects ................................................................................ 19 
14 Literature References .......................................................................................................... 20 

 
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1 
List of Abbreviations 
 
Abbreviation 
Abbreviation definition 
UVR 
Ultraviolet Radiation 
UVB 
Ultraviolet B Radiation 
25(OH)D 
25-hydroxyvitamin D 
SPS 
Solius Photobiologic System 
MED 
Minimal Erythemal Dose 
 
2 
Protocol Summary 
 
Title: 
Evaluating the effect of Solius Photobiological System in improving 
serum levels of 25-hydroxyvitamin D in vitamin D deficient/ 
insufficient adults: A feasibility study  
 
Population: 
Healthy adults ages 22 years and older; both sexes, approximately 
14 adults for serum 25-hydroxyvitamin D screening, 10 adults with 
vitamin D deficiency/insufficiency for the feasibility study 
Intervention: 
The study treatment is a weekly exposure to the Solius 
Photobiological System, which emits Ultraviolet B Radiation (UVB). 
This will be accomplished with an established dose of UVB radiation 
for 4 weeks. SOLIUS delivers 0.6 Minimal Erythemal Dose (MED) to 
achieve non-perceivable erythema for a therapeutic dose.  
  
Objectives: 
To assess the safety and effectiveness of the Solius Photobiological 
System in improving serum levels of 25-hydroxyvitamin D in vitamin 
D deficient/ insufficient adults of various skin types  
 
Design/Methodology: 
We will conduct an interventional study to determine the changes 
in serum 25-hydroxyvitamin D levels in subjects who received 
Ultraviolet B Radiation (UVB) generated by the Solius 
Photobiological System for 4 weeks. Subjects will first undergo an 
evaluation of each individual's sensitivity to the Solius 
Photobiological System UVB using the device titration system for 
the first 5 weeks.  Once determined after the 5 weeks, the 
subjects will be enrolled in a 4-week study where they will be 
exposed to their individualized titration evaluation. Approximately 
14 adult subjects will be enrolled for serum 25-hydroxyvitamin D 
screening. We expect to enroll 10 vitamin D-deficient or 
insufficient subjects in this study. Serum 25-hydroxyvitamin D 
levels will be measured prior to the first titration (week 2), prior to 
the intervention (week 6) and after end of the study, and the 
changes in serum 25-hydroxyvitamin D levels will be analyzed. We 
expect that the levels will increase from the baseline.  
Total Study Duration: 
6 months 

 
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Subject Participation Duration: 10 weeks including one week for screening, 5 weeks for titration, 4 
weeks for intervention 
 
3 
Background/Rationale & Purpose 
 
3.1 
Background Information 
 
Vitamin D deficiency has been a worldwide health problem for over a century, now affecting over 1 
billion people on this planet1. Although technology is drastically advancing, we still are unable to put an 
end to this health emergency.  
 
Vitamin D can be introduced in the body in two ways, 1) via diet and 2) through the sun. Few foods 
naturally contain vitamin D (either D2 or D3)2 such as oily fish. For instance fresh, wild salmon (3.5oz or 
100g) has between 600-1000 IU of vitamin D3. Canned tuna (3.6oz or 102 g) has about 230 IU of vitamin 
D3.2  Sun-dried mushrooms and egg yolks are also viable sources of vitamin D.  Sun-dried shiitake 
mushrooms have about 1600 IU of vitamin D2 whereas egg yolks have about 20 IU of vitamin D2 or 
vitamin D3 2. There are some fortified foods that also contain vitamin D; fortified milk and fortified 
orange juice each has about 100 IU/8 oz of vitamin D3. Some cereals, such as Quaker Oatmeal has as 
much as 40 IU vitamin D/cup.3 Margarine has about 60 IU of vitamin D/tablespoon.3 In a study that 
looked at the plasma levels of 25(OH)D3 amongst fish eaters and non-fish eaters (vegans and 
vegetarians), those who did not consume fish had lower levels of 25(OH)D3 in both the summer months 
(20%) and winter months (38%).4 Thus the consumption of fish in the diet is critical in maintaining 
vitamin D status throughout the year, especially during the winter months. 
 
When assessing the optimal dietary intake of vitamin D, there might be some controversy as to which 
guideline to follow. The Institute of Medicine (IOM) issued guidelines to maintain adequate serum 
25(OH)D levels above 20 ng/mL.5 The Endocrine Society’s guidelines reflect the needs to treat and 
prevent vitamin D deficiency and maintain a 25(OH)D status above 30 ng/mL.6 One would have to 
consume a significant amount of fish and fortified food products to meet the above recommendations. 
Thus it is critical that we incorporate sun exposure into our everyday lives, and/or take vitamin D 
supplements.  
 
When ultraviolet B (UVB) radiation (wavelength of 290-320 nm) from the sun is absorbed into the skin, it 
converts 7-DHC, which is predominantly located in the stratum spinosum and stratum basale7, to 
previtamin D3, which is thermodynamically unstable. Over several hours it isomerizes into vitamin D3.8  
The vitamin D3 from the skin and the vitamin D2 from food and supplements enters the circulation and 
are hydroxylated in the liver by a 25-hydroxylase to become 25-hydroxyvitaminD (25(OH)D), which is the 
major circulating form of vitamin D.8-9 25(OH)D is hydroxylated again in the kidneys by 1alpha-
hydroxylase to become 1,25-dihydroxyvitamin D (1,25(OH)2D), which is the active form of vitamin D. 
When calcium levels are too high, 24-hydroxylase activity increases, hydroxylating C24 and making, 
24,25-Dihydroxyvitamin D (24,25(OH)2D) and 1,24,25-trihydroxyvitamin D (1,24,25-(OH)3D). This step 
begins the process of the degradation of both metabolites into inactive water soluble metabolites that 

 
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can be excreted in the bile. The ability to maintain 25(OH)D levels via sun exposure is influenced by the 
zenith angle of the sun.10 The zenith angle is defined as the oblique angle between the sun’s rays and 
the earth’s surface. The time of day, season, and latitude on the earth’s surface all affect the zenith 
angle. Above 37 latitude during the months of November through February, there is a significant 
decrease in the amount of UVB photons hitting the earth’s surface, as much as 80%-100% depending on 
latitude 11. Thus, for those living in areas at a zenith angle incompatible for producing vitamin D in the 
winter, they need to obtain their vitamin D via supplements and/or food containing or fortified with 
vitamin D.  
 
Those living above 37 latitude during the months of November through February could also rely on 
artificial UVB light sources such as the Sperti lamp or UVB emitting LEDs. These lights permit the skin to 
convert 7-dehydrocholesterol into vitamin D allowing the body to maintain adequate vitamin D levels 
while avoiding exposure to the sun. In particular, these lights are resourceful to those having fat 
malabsorption disorders such as Crohn’s disease, cystic fibrosis, and/or gastric bypass. For these 
individuals who are unable to absorb vitamin D from the diet, exposure to UVB is the primary way of 
maintaining an adequate vitamin D status.  
 
UVB phototherapy is a potential solution to the problem. Importantly, narrowband UVB (NB-UVB) 
phototherapy can be safely used.  Long-term studies to date do not indicate a significantly increased risk 
of skin cancer in an age- and sex-matched control population who have not received UVB phototherapy. 
20-24 In a 2005 literature review, a search from 1966 to June 2002 was conducted.  Eleven studies 
involving about 3400 subjects (including those with >300 lifetime treatments) were included. Except for 
1 Finnish study, all studies showed no increased skin cancer risk with UVB phototherapy.25 In a 2012 
systematic literature review examining NB-UVB and risk of skin cancer, four studies followed a total of 
6,385 subjects. None of the four studies found an increased risk of skin cancer in psoriasis subjects 
treated with NBUVB. 26 The above studies were mostly in Caucasians with skin types I-III. In a 2011 study 
of 445 Koreans (skin type III-V) treated with NB-UVB, no melanoma cases were reported within the 
mean follow-up period of 34.4 months.27 The investigators also concluded that there were no 
statistically significant differences in non-melanoma skin cancer between the NB-UVB and control 
groups. In the largest study on the safety of vitiligo treatment ever conducted, a 2020 retrospective 
cohort enrolled 60,321 subjects with vitiligo. 28 Subjects were classified into 5 groups: 0 sessions of NB-
UVB; 1-49 sessions; 50-99 sessions; 100-199 sessions; and ≥200 sessions. 717 subjects had at least 500 
phototherapy sessions. The risk of nonmelanoma skin cancer did not increase with increasing total 
sessions of NB-UVB. Further, the subjects who had at least 500 sessions of NB-UVB phototherapy had no 
greater risk of skin cancer than the subjects who did not undergo NB-UVB phototherapy at all. 
 
Solius has created The Solius Photobiologic System (SPS), which is an experiential device that allows a 
user to receive a calibrated and calculated dose of vitamin D using wavelengths of UV light that facilitate 
the body’s endogenous production of vitamin D and a variety of biologically controlled feedback 
mechanisms. The output of SPS is very similar to a NB-UVB device, but without the wavelengths that are 
less effective in endogenous vitamin D production.  Exposure of individuals with varying skin types to 
these lights will enable us to observe the effect of artificial UVR  exposure in creating vitamin D in 
individuals with varying shades of skin color. The benefit of this lamp will allow individuals who live in 
northern locations or individuals with malabsorption problems to create vitamin D.  

 
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Solius previously has completed two human clinical trials. The first study was a pilot feasibility study 
aimed to validate if the Solius Photobiological System efficiently stimulated the endogenous vitamin D 
process. The second study was a randomized non-inferiority study comparing the SOLIUS device to oral 
vitamin D supplements.  
In a prospective cohort study (QR-TRP-002), six healthy adults with Fitzpatrick skin types I, II, and III were 
exposed to a 0.75 minimal erythemal dose (MED) of UVB radiation to approximately 75% of their body 
surface area once per week for 4 weeks. The individual dose was determined with Fitzpatrick skin 
typing, followed by exposure of the underneath of one forearm to 10 successively increasing durations 
of exposure to UVB. The subjects had a significant increase in mean 25(OH)D from 22.8 ± 13.9 ng/ml to 
27.2 ± 12.0 ng/ml (P<0.05), representing a 19% increase over baseline after 4 weekly UVB exposures. No 
adverse events occurred. 
Another study was performed on military personnel. Military personnel are at high risk for low vitamin D 
status which is common in individuals who regularly perform extreme physical exertion, particularly in 
combination with periods of psychological stress, inadequate nutrition, and sleep disruption. A total of 
98 participants enrolled in the study; 10 (10.2%) either dropped out or were removed after enrollment. 
The final sample included 45 participants in the supplement and 43 in the phototherapy group. There 
were no between group differences noted based on age or gender distribution (P=0.06). There were also 
no between group differences observed with respect to race / ethnicity, Fitzpatrick skin type, birth 
location with respect to 37th parallel, prior diagnoses of vitamin D deficiency, vitamin D 
supplementation history, stress fractures, or family history of bone disorders, and total number of hours 
per week of sun exposure, with P > 0.05 for these groups. 
The median serum 25(OH)D levels at baseline for the supplement and phototherapy were 25.0 ng/mL 
(IQR 21.0–32.0) and 28.0 ng/mL (IQR 22.0–35.0), respectively. By month three, the phototherapy group 
showed significantly higher levels of serum 25(OH)D than the supplement group (P=0.01, ŋ2=0.08) with 
a median level of 25.5 ng/mL (IQR 21.0–29.8) compared to a median level of 30.0 ng/mL (IQR 25.8-37.0) 
for the phototherapy group. By the four-month follow up the two groups again showed a slight 
difference in serum 25(OH)D levels with higher levels in the phototherapy group (P=0.04, ŋ2=0.05).  At 
this timepoint the supplement group had decreased from baseline to median levels of 21.0 ng/mL (IQR 
17.0-30.0) and phototherapy returned to baseline (median 27.0 ng/mL, IQR 22.0-32.5) (supplementary 
documents). 
With suboptimal intake of key nutrients like calcium and vitamin D, historically low compliance with 
taking pills, and low sun exposure, limited potential to optimize serum 25(OH)D continues to pose a 
threat to physical and mental health, disease prevention, and resilience so critical to individual wellness 
and readiness. At a time when self-care measures are highly valued for health promotion, programmed 
UVB photobiologic therapy, available as a kiosk in the community, appears to be a safe, efficacious 
alternative to oral vitamin D supplementation. 
 
As discussed above, there is an ever growing need to improve the vitamin D status of the global 
population. Many individuals who live above 37 latitude and/or have malabsorption problems will 
greatly benefit from an artificial light source to combat their increased risk for vitamin D deficiency. The 
purpose of this study is to observe the effects of exposure of individuals of varying shades of skin color 

 
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to Solius light source. The findings from the study have enormous health implications as it could be a 
potential treatment plan for many people battling vitamin D deficiency.8,11,13 
 
This study will be conducted in compliance with the protocol, applicable regulatory requirements, and 
BMC/BU Medical Campus Human Research Protection policies and procedures. 
 
3.2 
Rationale and Purpose  
 
We aim to conduct this feasibility study in anticipation of conducting a more extensive study that will be 
used to evaluate the safety and efficacy of the Solius Photobiologic system for improvement of vitamin 
D status. 
 
4 
Objectives 
 
4.1 
Study endpoint 
 
The endpoints are to gain experience in using this device to determine if exposure to UVB generated by 
the Solius Photobiologic system will lead to some improvement in vitamin D status.  
 
Study Outcome Measures 
 
Improvement of serum levels of 25(OH)D will be measured by 25(OH)D analysis at baseline,  
prior to the intervention (week 6) and the end of the study.  Serum 25(OH)D levels 
measurement will be performed by Quest Diagnostics. 
 
4.1.1 Endpoint Measures 
 
1. At each visit, the subjects will be asked to report any adverse events and any skin changes.  
These adverse events will be tabulated and reported at the study completion. 
2. Blood samples will be obtained from all subjects at baseline (prior to the first titration, week 2),  
prior to the intervention (week 6) and end of the study. Blood samples will be sent to the Quest 
Diagnostics or to the Boston Medical Center’s clinical laboratory for determining the serum 
25(OH)D levels.  
 
 

 
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5 
Study Design 
 
This is a pilot interventional study aiming to gain experience in using of the Solius Photobiologic System 
that is designed to increase the serum levels of 25(OH)D in a vitamin D deficient/insufficient adult 
population. We will make our best effort to recruit individuals with different Fitzpatrick skin types. The 
study will be conducted at Boston University after it is approved by Boston University’s Institutional 
Review Board. The use of a single location will keep uniform natural UVB exposure of the study as opposed 
to multiple geographic locations what would create a wide variety of natural exposures to UVB and result 
in a less uniform impact of this natural exposure in both study arm. 
 
Table 1.  The below guidelines will be used to make this distinction:  
 
Table 1: Fitzpatrick Skin Types 
Skin 
type 
Typical Features 
Tanning ability 
I 
Pale white skin, blue/green eyes, blond/red hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
 
 
Each subject will be categorized into one of 6 Fitzpatrick skin types, type I, II III, IV and skin type V or VI. 
Skin types V and VI will be combined to represent the group with the darkest skin tone for subgroup 
analysis.  
 
A total of 14 adult subjects with 5 skin types groups (I, II, III, IV and V/ VI) will be enrolled for vitamin D 
deficiency/ insufficiency screening.  The screening test for 25(OH)D will be performed by the Boston 

 
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Medical Center’s clinical laboratory which is able to perform the test within 24 hours.  We expect at least 
80% of the population in the Boston area has a level of 25(OH)D below 30 ng/ml. Thus, we expect to enroll 
approximately 14 subjects with different group skin types to enroll 10 vitamin D deficient or insufficient 
subjects in this study to receive UV exposure by the Solius Photobiologic System. The device will have a 
strip of colored LED installed inside the light towers. Both UV lamps and purple LED will turn on during the 
treatment.  
 
Blood samples will be obtained prior to the first titration (week 2) , prior to the intervention (week 6) 
and end of the study. The blood samples will be sent to Quest Diagnostics or the Boston Medical 
Center’s clinical laboratory for determining the serum 25(OH)D levels. The study design is summarized in 
Table 2. 
 

 
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Table 2. Outcomes measurement at each time point of the study for both study groups 
 
 
 
6 
Potential Risks and Benefits 
 
6.1 
Risks 
 
The main acute adverse effects of narrowband UVB (NB-UVB) are erythema and induction of 
photosensitivity diseases, such as polymorphic light eruption (PLE). Although the risk of erythemal 
episodes may be increased by concomitant phototoxic drugs14,15, this can be minimized by undertaking a 
baseline minimal erythema dose (MED) and establishing treatment protocols based on an individual's 
MED16. This also allows any unsuspected abnormal photosensitivity diseases to be detected, in particular 
solar urticaria or chronic actinic dermatitis (CAD). Induction of PLE may occur during a treatment course 
but generally can be accommodated via dose adjustments and judicious use of topical corticosteroid, 
without the need to stop NB-UVB17. Other uncommon side-effects, such as psoriatic lesional blistering, 
occasionally occur but generally treatment is very well-tolerated18,19.  
 
Overexposure to our artificial UVB source may incur similar symptoms to a mild sunburn (slight reddish 
coloration to the skin). The Solius Photobiological System was designed to minimize total UVB exposure 
to minimize the potential for sunburn. To make sure subjects do not develop redness (erythema) or 
psoriatic lesional blistering, the exposure will set for the lamp to 60% or 0.60 of the minimal erythemal 
dose (MED) for each individuals’ skin type. 
 
Over exposure to the UVB to the eyes may cause photokeratitis.  
 
To prevent the overexposure, the subject’s dosage will be determined during titration period. Eye 
protection will be provided to the subjects before each treatment. The device software will require 
subject confirmation that is in place before treatment can be delivered. 
As the appropriate doses are individualized to the subject, to establish the correct dose, each subject 
will complete a titration period of up to 5 weeks.  The titration period will start with an erythemally 
weighted dose of 10.53 mJ/cm2 to 43.07 mJ/cm2 (depending on skin type) and increase by 26 – 36% 
Activity 
Baseline 
Wk 1 
Titration  
Intervention  
Wk 2 
Wk 3 
Wk 4 
Wk 5 
Wk 6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
Demographics/ 
Skin typing 
X 
 
 
 
 
 
 
 
 
 
UVB Exposure 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
25(OH)D  
X 
X 
 
 
 
 
X 
 
 
X 
Sun exposure/ 
Vit. D food 
checklist 
X 
X 
 
 
 
 
 
 
 
X 
Concomitant 
Medications 
X 
X 
 
 
 
 
X 
X 
X 
X 
Adverse Events 
 
X 
 
 
 
 
X 
X 
X 
X 

 
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each step until a maximum erythemally weighted dose of 34.88 mJ/cm2 – 109.33 mJ/cm2 (depending 
on skin type) or the subject shows a skin reaction.  This dose will be the subject’s dosage.   
 
The subject’s dosage will be administered under conditions of full-body exposure (males in swimming 
trunks or briefs and females in bikini or bra and panties) of 0.6 minimal erythemal dose (MED) once per 
week for 4 weeks. At each visit, the subject will report adverse events and any skin changes.   
 
We will have the blood samples drawn by trained professionals to minimize the risk of hematoma 
formation, bleeding, or infection at the site of needle insertion. Study staff will update subjects in a 
timely way on any new information that may affect their health, welfare, or decision to stay in this 
study. Any and all side effects reported will be recorded in the subjects' file in the study binder. Subjects 
will be instructed to call the study staff or PI immediately if any side effects do occur. The PI will advise 
the subjects according to the symptoms reported. After the determination, all samples will be 
de-identified. The PI will be available to answer any questions or concerns from potential subjects prior 
to consenting. We have a plan to protect subject privacy and confidentiality, which is explained in the 
plan to protect subject privacy and confidentiality in the data section. 
 
Vitamin D deficiency and insufficiency is common in adults due to an inadequate dietary intake of 
vitamin D and or inadequate sun exposure.  Chronic vitamin D deficiency and insufficiency can lead to 
bone loss resulting in increased risk of fracture later in life.  Chronic vitamin D deficiency can also cause 
a mineralization defect of the skeleton resulting in osteomalacia.  Short term (10 weeks) vitamin D 
deficiency and insufficiency is not associated with significant bone loss or osteomalacia. Therefore, the 
participants are at no increased risk for fracture or osteomalacia.  At the termination of this study those 
participants will be encouraged to take a vitamin D supplement along the guidelines recommended by 
the Endocrine Society to correct their vitamin D deficiency and insufficiency.   
 
Chronic excessive exposure to sunlight or ultraviolet radiation for prolonged periods of time, in years or 
decades, can increase risk for nonmelanoma skin cancer.  To minimize the risk the subjects will be 22 
years and older and will be exposed to suberythemal doses of UVB radiation for the duration of the 
study 
 
6.2 
Potential Benefits 
 
The study participants may receive no benefit. However, possible benefits include an increase in vitamin 
D status or resolution of vitamin D deficiency/insufficiency. However, subjects may not receive any 
benefit.  The subjects’ being in the study may help the investigators evaluate whether the SoliusONE 
device is safe and effective in increasing blood levels of 25-hydroxyvitamin D and treating vitamin D 
deficiency/insufficiency. Subjects will not be responsible for any research related costs. They will receive 
compensation in each of their visit, which is shown below. Parking vouchers or transportation cost are 
available for each visit.  
 
 
 
 
 
 
 

 
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Note: BD: Blood draw; UV: Ultraviolet B radiation exposure; PV: Parking voucher  
 
6.3 
Analysis of Risks in Relation to Benefits 
 
Highly trained professionals will be performing the blood draws which is likely to be a chance of risk. The 
adverse skin reaction from the Solius Photobiological System such as skin erythema and pruritus is a 
possible risk in this study. However, this study will expose the participants to a relatively low intensity of 
UVB (0.6 MED), so the risk of adverse reaction is minimal. All the participants will be asked for their 
willingness to receive the intervention at every exposure and will be questioned and examined for any 
potential adverse reaction due to the intervention. If any significant adverse reaction is detected, the 
intervention will immediately stop and the affected participant will receive immediate medical 
attention. Significant adverse reactions include photokeratitis, moderate to severe skin tenderness, 
itchness and tightening, skin blistering, or bruising or tearing of skin. The risks of breach of 
confidentiality are highly unlikely, and therefore benefits will greatly outweigh the risks. 
 
7 
Study Subject Selection 
 
7.1 
Subject Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Age at least 22 years old 
2. Male or Female 
3. Skin Type I-VI 
4. Women of child bearing potential must be on birth control and not pregnant based on a negative 
pregnancy test at baseline. 
5. Ability and Willingness to give informed consent and comply to protocol requirements 
6. Serum total 25(OH)D < 30 ng/mL  
 
7.2 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Ongoing treatment with supplemental or pharmacological doses of vitamin D, vitamin D 
metabolites or analogues 
2. Pregnant 
3. History of underlying photosensitivity  
4. Use of medications that cause a photosensitivity reaction (including but not limited to): 
tetracycline, tretinoin, amiodarone, doxycycline, naproxen, diphenhydramine, methotrexate, 
and hydrochlorothiazide 
5. History of skin cancer 
6. Plan to received significant sun exposure below the 33rd parallel during study  
7. Used tanning or phototherapy devices within the last 30 days 
8. Vitamin D supplement use of more than 600 IUs daily.   
Study 
group/activity 
Screening 
visit 
Wk 1 
Titration 
Intervention  
Total 
Wk 2 
Wk 3 
Wk 4 
Wk 5 
Wk 6 
Wk 7 
Wk 8 
Wk 9 
Wk 10 
 
Activity  
Screening 
Consent 
BD 
BD 
UV 
UV 
UV 
UV 
UV 
 
BD *2 
UV 
 
UV 
UV 
UV 
BD*2 
$750 
Up to 
$1,050 
Compensation 
$100 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$250 
Transportation 
cost 
PV or $30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
PV or 
$30 
Up to 300 

 
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9. Systemic steroids use  
10. H1 antihistamine use in the last 7 days  
11. Diagnosed with light allergies (including but not limited to): actinic prurigo, polymorphous light 
eruption, or solar urticaria 
12. Diagnosed with light sensitivities (including but not limited to): protoporphyria, photodermatitis,  
xeroderma pigmentosum, lupus erythematosus, chronic actinic dermatitis, or UV-sensitive 
syndrome 
 
8 
Study Intervention 
 
Subjects (n=10) will be exposed to the Solius Photobiological System which includes exposure to visible 
purple LEDs and invisible UVB radiation. The study intervention will involve an investigational UVB 
emitting device, The Solius Photobiologic System created by Solius. The Solius Photobiological System 
emits UVB.  To make sure subjects do not develop redness, the exposure will set for the lamp to 60% or 
0.60 of the minimal erythemal dose (MED) for each individual’s skin type.  
 
As the appropriate doses are individualized to the subject, to establish the correct dose, each subject 
will complete a titration period of up to 5 weeks.  The titration period will start with an erythemal 
weighted dose of 10.53 mJ/cm2 to 43.07 mJ/cm2 (depending on skin type) and increase by 26 – 36% 
each step until a maximum erythemal weighted dose of 34.88 mJ/cm2 – 109.33 mJ/cm2 (depending on 
skin type) or the subject shows a skin reaction.  This dose will be the subject’s dosage.   
 
The device will have a strip of purple LEDs installed inside the light towers. Both UV lamps and purple 
LEDs will turn on during the treatment. According to a previous study by Solius where 43 subjects were 
exposed to a 0.6 MED, the stimulation of cutaneous vitamin D and subsequent increase in serum 
concentrations of 25(OH)D  from phototherapy was compared to the effect of a Recommended Daily 
Allowance (RDA) based dose of 600 IU vitamin D3 supplement daily for 10 weeks.  Thus, we will expose 
these individuals a 0.6 MED once per week for 4 weeks to observe the effect on 25(OH)D serum 
concentration.  
 
9 
Study Procedures 
 
We will advertise for this study at the Boston University Medical campus via email newsletters and 
advertisements on various TV screens. Once subjects have responded to the study flyer and contacted 
study staff, they will be screened over the phone to determine eligibility. During the preliminary 
screening telephone call, the subject will be asked about their medical history and inclusion/exclusion 
criteria. For the subjects who are determined to be eligible, they will be assigned with a study ID and 
their answers to the questions will be documented in the study binder. Eligible subject’s contact 
information and identifier will be kept separate from the answers. For individuals with screening failure, 
no answer or identifiable information will be retained.  
 
Eligible subjects be scheduled for their first visit to Boston University Medical Center’s General Clinical 
Research Unit at 80 E. Concord St or in the clinical research space in the Vitamin D, Skin, and Bone 
Research Laboratory located at 85 E Newton St, M-1013 Boston, MA 02118. The study coordinator or 
IRB-approved research assistants will consent the subjects. Dr. Holick will not participate in consenting 
the subjects, but will be available to answer any questions or concerns that the subjects may have 
during the process. We will ask the subjects to read and ask any questions in regards to the screening 

 
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process that they have prior to signing the consent form. This consent form will also allow us to conduct 
a urine pregnancy test on women of child bearing potential, perform a 25(OH)D blood screen, and 
conduct our study experiment. Researchers will document that consent was given in our consent form 
log sheet where (s)he will need to sign and date that informed consent was given and that the subject 
received a copy of the ICF.  
 
Approximately 14 adult subjects with 5 skin types groups (I, II, III, IV and V/ VI) will be enrolled for 
vitamin D deficiency/ insufficiency screening. We expect at least 80% of the population in the Boston 
area has a level of 25(OH)D below 30 ng/ml. Thus, we will enroll approximately 14 subjects with 
different group skin types to enroll 10 vitamin D deficient or insufficient subjects in this study. All of the 
subjects will receive the UVB intervention. The device will have a strip of colored LED installed inside the 
light towers. Both UV lamps and colored LED will turn on during the treatment. To elaborate further, all 
subjects will use the same device with the exact same workflow on the touchscreen user interface. The 
experience in starting a SOLIUS session, answering the safety questions, automatic dispensing of 
eyewear, etc. will be the same for all subjects. This is achieved by adding an independent software 
branch to the existing system that replicates the user workflow code but only turn on the LED drivers. 
LED strips are added to the existing light tower, and the lights will project through the same light path as 
the UV lamps. As a result, visible purple light will be emitted from the same emitting window as the UV 
lamps.   
 
Blood samples will be obtained prior to the first titration (week 2), prior to the intervention (week 6) and 
end of the study. The blood samples for the screening will be performed by the Clinical Laboratory at 
Boston Medical Center which will be able to provide the test result within 24-48 hours.  The blood 
samples for the study collected after screening, will be sent to Quest Diagnostics for determining the 
serum 25(OH)D levels. The study design is summarized in Table 2. 
 
Each subject will be advised to come in for five titration visits.  The purpose of these visits to establish 
the correct UVB dose in the SoliusONE device.  At these visits, each subject will be asked questions 
about consumption of vitamin D, sun exposure, and whether he/she has had any adverse changes in 
his/her health.  After the titration visit, each subject will complete a 4-week course of SoliusONE 
treatment.  During each titration/treatment session, the study personnel will record subject’s 
information in the application that is installed in the study personnel’s smartphone. The information to 
be recorded include subject ID, age and sex. This allows the software to link to database and create user 
profiles for dosing. None of the identifiable information will be recorded in the application. Then, each 
subject will stand in the SoliusONE device while exposed to UVB light. Each subject will be asked to wear 
a swimsuit, swimming trunks (for males) or bikini (for females) while being exposed to UVB in the 
device.  The device is large enough so that the participant is able to remove their clothing and to hang it 
up on a hook that is provided in the device.  If they are wearing their bathing suit, they will then be 
exposed to the UVB light.  If they have brought their bathing suit with them, they will be able to put it on 
in the device and then be exposed to the UVB light.  They then have the option of keeping the bathing 
suit on and dressing or removing the bathing suit and putting on all of their undergarments and clothing 
before exiting the device.  For those who either do not want to wear a bathing suit under their clothing 
or have forgot to bring their bathing suit then they will have the option of being exposed to the UVB in 
their underwear (males in their underwear shorts and females in their panties and bra). Each session will 
take approximately 2-10 minutes depending on the subject’s skin type group (lighter skin type groups 

 
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require less treatment time). Before and after each treatment, the device will be cleaned using 
disinfectant to ensure proper hygiene. 
 
Blood samples will be obtained from all subjects at baseline (prior to the first titration, week 2), prior to 
the intervention (week 6) and end of the study. Blood samples will be sent to Quest Diagnostics for 
determining the serum 25(OH)D levels. The study design summarized in Table 2 
 
If a subject needs to end his/her regimen early they will be able to do so, with no change to the study 
procedure. We will require a final blood sample collection from the study subject prior to his/her 
removal.  
 
We anticipate the entire study will take 6 months to complete. As discussed earlier the study subject’s 
involvement will last 10 weeks from screening to completion include one week for screening, 5 weeks 
for titration, 4 weeks for treatment.  
 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) 
 
10.1 Definitions 
 
The following definitions will be used in the assessment of safety: 
 
Adverse Event (AE) is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research. 
 
Serious Adverse Event (SAE) is any adverse event that  
(1) results in death; 
(2) is life-threatening; 
(3) results in subject hospitalization or prolongation of existing hospitalization; 
(4) results in a persistent or significant disability/incapacity; 
(5) results in a congenital anomaly/birth defect;  
(6) based upon appropriate medical judgment, may jeopardize the subject's health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition 
(examples of such events include allergic bronchospasm requiring intensive treatment in the 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse).  
 
Life-threatening means that the event places the subject at immediate risk of death from the event as it 
occurred.  
 
Unanticipated Problem is defined as an event, experience or outcome that meets all three of the 
following criteria:  
• 
is unexpected; AND 
• 
is related or possibly related to participation in the research; AND 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  

 
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Possibly related means there is a reasonable possibility that the incident, experience, or outcome may 
have been caused by the procedures involved in the research 
 
Unexpected means the nature, severity, or frequency of the event is not consistent with either: 
• 
the known or foreseeable risk of adverse events associated with the procedures involved in the 
research that are described in (a) the protocol–related documents, such as the IRB-approved 
research protocol, any applicable investigator brochure, and the current IRB-approved informed 
consent document, and (b) other relevant sources of information, such as product labeling and 
package inserts; or 
• 
the expected natural progression of any underlying disease, disorder, or condition of the 
subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the 
adverse event. 
 
10.2 Safety Review 
 
Dr. Shirvani or Dr. Charoenngam will interview the subjects before their next exposure each week for any 
adverse events including erythema or any other skin reactions as shown in the table. At the time of the 
evaluation, it will be determined whether the subject will continue with the next exposure or whether the 
subject will be removed from the study. This will be based on the determination of the degree of erythema 
or adverse skin reaction.  Dr. Alan Farwell will serve as an Independent Scientific Reviewer (ISR). He will 
provide an assurance that the findings and conclusions reached are supported by the data presented, and 
also, to assure that the content is consistent with applicable scientific standards and  will be responsible 
for a review of the data analysis, data interpretation and/or presentations and manuscripts. 
 
The following known side effects of UVB will be monitored: 
Side effect 
Signs/symptoms 
Instruction for subjects on 
monitoring 
Sunburn 
Pain, tenderness of the 
skin, redness, tightness, 
itching, and rarely 
blistering 
 
Check for pain and redness 4-6 
hours after treatment. If there 
is severe pain, should seek 
medical attention.  
 
If there are blisters, should seek 
medical attention 
Photoaging 
Atrophic skin, coarseness, 
fibrotic areas, increased 
fragility, laxity, mottled 
pigmentation, 
telangiectasias, wrinkling 
If there is increased fragility (i.e. 
easy bruising or tearing of skin), 
then should seek medical 
attention.  The other 
photoaging side effects are 
benign and more of a cosmetic 
nature.  
 
Tanning  
Skin darkening 
As a benign side effect, no 
subject monitoring is needed 

 
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In addition, Prior to each treatment, Solius software will prompt the user with the following questions to 
assess erythema: 
 
1. Did you observe any pinkness (similar to sunburn) after your last treatment? (yes / no) 
2. Did the pinkness last for more than 3 days? (yes / no) 
3. Did you experience any pain or discomfort (excluding itch) with the pinkness? (none / mild / 
moderate/severe) 
 
Based on the user’s response, the software could maintain current dose, reduce dose, or block account 
for further investigation. The PI or Dr. Shirvani or Dr. Charoenngam will be notified to perform further 
assessment if an account was blocked by the software.  
 
10.3 Reporting Plans 
 
The Principal Investigator at BMC/BU Medical Campus will report Unanticipated Problems, safety 
monitors’ reports, and Adverse Events to the BMC/BU Medical Center IRB in accordance with IRB 
policies: 
• 
Unanticipated Problems occurring at BMC/BU Medical Campus involving a fatal or life-threatening 
event will be reported to the IRB within 2 days of the investigator learning of the event. 
• 
Unanticipated Problems occurring at BMC/BU Medical Campus not involving a fatal or life-
threatening event will be reported to the IRB within 7 days of the investigator learning of the 
event. 
• 
Reports from safety monitors with recommended changes will be reported to the IRB within 7 
days of the investigator receiving the report.  
• 
Adverse Events (including Serious Adverse Events) will be reported in summary at the time of 
continuing review, along with a statement that the pattern of adverse events, in total, does not 
suggest that the research places subjects or others at a greater risk of harm than was previously 
known. 
• 
Reports from safety monitors with no recommended changes will be reported to the IRB at the 
time of continuing review.  
 
10.4 Stopping Rules 
 
A subject will be withdrawn from the study if refuse to participate, or if subject’s serum 25(OH)D level is 
more than 100 ng/mL, or if the subject undergoes an adverse reaction to the light source e.g. skin 
erythema or pruritus.  
 
11 Data Handling and Record Keeping 
 
11.1 Confidentiality 
 
Subjects are assigned a code after consent and enrolled in the study. All coded records containing subject 
information will be stored in Dr. Holick’s offices under lock and key. The blood samples will be kept in the 
Dr. Holick lab (M-1011). The door to the Vitamin D lab is accessed by those who have ID access to the lab. 

 
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The data will be coded and after 7 years will be deidentified and kept indefinitely. Electronic information 
will be stored on a departmental server ("Y"drive) and "C" drive of study coordinator's computer both of 
which are password protected. Paper records will be stored in a locked room for which only study staff 
will have access to. Master list will be stored on the study coordinator’s PC and will not be stored with 
study data. All other electronic data will be on the PC of the study coordinator, which is password 
protected. Paper master list will be stored and locked in M1013; only study staff and study coordinator 
have access to this room. All locations where data will be kept are inaccessible to the public. Data will be 
available only to study personnel. Data will be kept in a locked room. Study code will be used for all study 
data that is collected. The study coordinator and study staff will keep the subject list on their computer, 
which is password accessible only. 
 
The study monitor or other authorized representatives of the sponsor may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the subjects in this study. The clinical study site will 
permit access to such records. 
 
11.2 Source Documents 
 
Data generated by the methods described in the protocol will be recorded in the subjects' medical 
records and/or study progress notes. Data may be transcribed legibly on CRFs supplied for each subject 
or directly inputted into an electronic system or any combination thereof. 
 
11.3 Case Report Forms 
 
The study case report form (CRF) will be the primary data collection instrument for the study. All data 
requested on the CRF will be recorded. All missing data will be explained. If a space on the CRF is left 
blank because the procedure was not done or the question was not asked, “N/D” will be written. If the 
item is not applicable to the individual case, “N/A” will be written. All entries will be printed legibly in 
black ink. If any entry error has been made, to correct such an error, a single straight line will be drawn 
through the incorrect entry and the correct data will be entered above it. All such changes will be 
initialed and dated.  There will be no erasures or white-out on CRFs.  For clarification of illegible or 
uncertain entries, the clarification will be printed above the item, then initialed and dated.  
 
See the Appendix for the following CRFs: Study Visit Report Form 
 
11.4 Study Records Retention 
 
All coded records containing subject information will be stored in Dr. Holick’s offices under lock and key. 
The blood will be kept in the Dr. Holick lab (M-1021A). The door to the Vitamin D lab is accessed by those 
who have ID access to the lab. The blood samples and data will be de-identified and kept indefinitely. They 
may be used for possible additional research in the future. Electronic information will be stored on a 
departmental server ("Y"drive) and "C" drive of study coordinator's computer both of which are password 
protected. Paper records will be stored in a locked room for which only study staff will have access to. 
Master list will be stored on the study coordinator’s PC and will not be stored with study data. All other 
electronic data will be on the PC of the study coordinator, which is password protected. Paper master list 
will be stored and locked in M1013; only study staff and study coordinator have access to this room. All 
locations where data will be kept are inaccessible to the public. Data will be available only to study 

 
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personnel. Data will be kept in a locked room. Study code will be used for all study data that is collected. 
The study coordinator and study staff will keep the subject list on their computer, which is password 
accessible only. Study records will be retained for at least seven years after completion of the study. 
Documentation of informed consent of subjects will be retained for at least seven years after the study is 
closed, unless the IRB waived the requirement for informed consent or documentation of informed 
consent. Such records may be preserved in hardcopy, electronic or other media forms and must be 
accessible for inspection and copying by authorized individuals.  
 
 
12 Statistical Plan 
12.1 Statistical analysis  
Data will be analyzed using the statistical software package SPSS (SPSS Institute, Chicago, USA). Serum 
levels of 25(OH)D will inspect for normal distribution using the Kolmogorov-Smirnov test, homogeneity 
of the variance (Levene-test), and outliers. The results will present as mean±standard deviation, or 
median. 
Serum levels of 25(OH)D will be compared before and after the study using the paired Student’s t-test 
(for normal distribution) or Wilcoxon test for repeated measures. Also, controlling for putative 
confounders such as skin type and sex, we will employ univariate general linear models (GLM) for the 
25(OH)D levels. Significant P-value will consider <0.05. 
 
12.2 Study Hypotheses 
 
We expect that with the incorporation of a 4-week phototherapy regiment, subjects will increase their 
serum 25(OH)D levels. In particular, we expect individuals with Fitzpatrick Type I and II skin to show the 
greatest response to phototherapy.  
 
12.3 Sample Size Determination 
 
A previous study by Chandra et al. demonstrated the increase in the mean serum 25(OH)D in subjects 
with malabsorption syndrome receiving UV therapy from 21± 3 ng/mL to 27±4 ng/mL.  According to this 
previous study, we postulate the mean and standard deviation of serum 25(OH)D before and after the 
intervention.  
To achieve a power of 90% and a level of significance (α) of 0.05 (two sided), for detecting a mean of the 
differences of 6 between pairs, assuming the standard deviation of the differences to be 4, the sample 
size in this  feasibility  is 8.  
 
We expect that 80% of the population in the Boston area has a level of 25(OH)D below 30 ng/ml. Thus, 
we have to enroll approximately 14 subjects with different group skin types to enroll 10 vitamin D 
deficient or insufficient subjects in this study. In our experience, the rate of screen failure and patient 
dropout is 10-15%. Then, we expect to have at least 8 subjects at the end of the study to achieve the 
desired power. 
 
  
13 Ethics/Protection of Human Subjects 
 
This study is to be conducted according to applicable US federal regulations and institutional policies 
(which are based in federal regulations, guidance, and ICH Good Clinical Practice guidelines). 

 
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This protocol and any amendments will be submitted to the Boston Medical Center and Boston 
University Medical Campus IRB, for formal approval of the study conduct. The decision of the IRB 
concerning the conduct of the study will be made in writing to the investigator.  
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. The 
consent form will be submitted with the protocol for review and approval by the IRB. The consent of a 
subject, using the IRB-approved consent form, must be obtained before that subject is submitted to any 
study procedure. Consent will be documented as required by the IRB.   
 
14 Literature References 
 
1. Holick MF, Chen TC. Vitamin D deficiency a worldwide problem with health consequences. Am J 
Clin Nutr 2008; 87;10805-68 
2. Holick M. Evolution and function of vitamin D. Recent Results Cancer Research. 2002;164:3-28. 
3. Office of Dietary Supplements - Vitamin D. https://ods.od.nih.gov/factsheets/VitaminD-
HealthProfessional/. Accessed March 14, 2016. 
4. Crowe FL, Steur M, Allen NE, Appleby PN, Travis RC, Key TJ. Plasma concentrations of 25-
hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC–
Oxford study. Public Health Nutrition. 2011;14(02):340-346. doi:10.1017/S1368980010002454. 
5. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies 
Press; 2011. http://www.nap.edu/catalog/13050. Accessed March 19, 2016. 
6. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of 
Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical 
Endocrinology & Metabolism. 2011;96(7):1911-1930. doi:10.1210/jc.2011-0385. 
7. Moody JP, Humphries CA, Allan SM, Paterson CR. Determination of 7-dehydrocholesterol in 
human skin by high-performance liquid chromatography. Journal of Chromatography B: 
Biomedical Sciences and Applications. 1990;530:19-27. doi:10.1016/S0378-4347(00)82298-7. 
8. Holick MF. Vitamin D Deficiency. New England Journal of Medicine. 2007;357(3):266-281. 
doi:10.1056/NEJMra070553. 
9. Reichrath J. Sunlight, Vitamin D and Skin Cancer. New York, NY: Springer New York; 2014. 
10. Kearns MD, Binongo JNG, Watson D, et al. The effect of a single, large bolus of vitamin D in 
healthy adults over the winter and following year: a randomized, double-blind, placebo-
controlled trial. European Journal of Clinical Nutrition. 2015;69(2):193+. 
11. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, 
cancers, and cardiovascular disease. American Journal of Clinical Nutrition. 2004;80(6):1678S - 
1688S. 
12. Holick, M.F., Chen, T.C., Sauter, E.R.  Vitamin D and Skin Physiology:  A D-Lightful Story.  J Bone 
Miner Res. 2007. 22(S2):V28-V33.   
13. Chandra P, Wolfenden LL, Ziegler TR, et al. Treatment of vitamin D deficiency with UV light in 
patients with malabsorption syndromes: a case series. Photodermatol Photoimmunol 
Photomed. 2007;23(5):179-85. 

 
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17. Man I, Dawe RS, Ferguson J. Artificial hardening for polymorphic light eruption: Practical points 
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18. Calzavara-Pinton PG, Zane C, Candiago E, Facchetti F. Blisters on psoriatic lesions treated with 
TL-01 lamps. Dermatology (2000) 200:115–9. 10.1159/000018342  
19. George SA, Ferguson J. Lesional blistering following narrowband (TL-01) UVB phototherapy for 
psoriasis: a report of four cases. Br J Dermatol. (1992) 127:445–6. 10.1111/j.1365-
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20. Archier E, Devaux S, Castela E, Gallini A, Aubin F, Le Maitre M, et al. . Carcinogenic risks of 
psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic 
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21. Man I, Crombie IK, Dawe RS, Ibbotson SH, Ferguson J. The photocarcinogenic risk of narrowband 
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22. Hearn RMR, Kerr AC, Rahim KF, Ferguson J, Dawe RS. Incidence of skin cancers in 3867 patients 
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23. Ibbotson SH. A Perspective on the Use of NB-UVB Phototherapy vs. PUVA Photochemotherapy. 
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24. Bae JM, Ju HJ, Lee RW, Oh SH, Shin JH, Kang HY, Park JH, Kim HJ, Jeong KH, Lee HJ, Lee S, Kim 
DH, Lee DY, Kim YC, Choi GS, Kim KH, Park CJ, Choi CW; Korean Society of Vitiligo.Evaluation for 
Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-term Narrowband UV-B 
Phototherapy. JAMA Dermatol. 2020 May 1;156(5):529-537. 
25. Int J Dermatol. 2005 May;44(5):355-60. UVB phototherapy and skin cancer risk: a review of the 
literature. Lee E1, Koo J, Berger T. 
26. J Eur Acad Dermatol Venereol. 2012 May;26 Suppl 3:22-31. doi: 10.1111/j.1468-3083.2012.04520.x. 
Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a 
systematic literature review. Archier E1, Devaux S, Castela E, Gallini A, Aubin F, Le Maître M, Aractingi S, 
Bachelez H, Cribier B, Joly P, Jullien D, Misery L, Paul C, Ortonne JP, Richard MA. 
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28. JAMA Dermatol . 2020 Mar 11;156(5):1-9. doi: 10.1001/jamadermatol.2020.0218. Online ahead 
of print. Evaluation for Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-
term Narrowband UV-B Phototherapy Jung Min Bae 1, Hyun Jeong Ju 1, Ro Woo Lee 1, Sang Ho 
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