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
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 concentrations of 25-hydroxyvitamin D in vitamin D 
deficient/ insufficient adults of various skin types 
 
ClinicalTrials.gov number: NCT04780776 
Protocol Version Number: 2.0 
Protocol Version Date: November 5th, 2020  
Funding Mechanism: Provided by SOLIUS company 
  
Principal Investigator: Dr. Michael F. Holick 
 
Phone: (617) 358-6139 
 
E-mail: mfholick@bu.edu 
Study Coordinator: Engie Gobran 
85 E Newton St, M-1013 
Boston, MA 02118 
P: (617) 358-6139 
Email: engie@bu.edu  
 
Statistical Analysis Plan see pages 23-26 
 
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 ................................................................................................................................ 8 
4.1 
Study endpoint .............................................................................................................. 8 
4.1.1 
Endpoint Measures ........................................................................................ 8 
5 Study Design ........................................................................................................................... 9 
6 Potential Risks and Benefits ............................................................................................... 13 
6.1 
Risks ............................................................................................................................. 13 
6.2 
Potential Benefits ........................................................................................................ 15 
6.3 
Analysis of Risks in Relation to Benefits ................................................................. 16 
7 Study Subject Selection ...................................................................................................... 16 
7.1 
Subject Inclusion Criteria ........................................................................................... 16 
7.2 
Subject Exclusion Criteria ......................................................................................... 17 
8 Study Intervention ................................................................................................................ 17 
9 Study Procedures ................................................................................................................. 18 
10 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ................................ 20 
10.1 Definitions .................................................................................................................... 20 
10.2 Safety Review ............................................................................................................. 21 
10.3 Reporting Plans .......................................................................................................... 21 
10.4 Stopping Rules ............................................................................................................ 22 
11 Data Handling and Record Keeping .................................................................................. 22 
11.1 Confidentiality .............................................................................................................. 22 
11.2 Source Documents ..................................................................................................... 23 
11.3 Case Report Forms .................................................................................................... 23 
11.4 Study Records Retention .......................................................................................... 23 
12 Statistical Plan ...................................................................................................................... 23 
12.1 Study Hypotheses ...................................................................................................... 24 
12.2 Sample Size Determination ...................................................................................... 24 
13 Ethics/Protection of Human Subjects ................................................................................ 26 
14 Literature References .......................................................................................................... 26 

 
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1 
List of Abbreviations 
 
Abbreviation 
Abbreviation definition 
UVR 
Ultraviolet Radiation 
UVB 
Ultraviolet B  
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 concentrations of 25-hydroxyvitamin D in vitamin D 
deficient/ insufficient adults  
 
Population: 
Healthy adults ages >21 years; both sexes, approximately 100 adults 
for serum 25-hydroxyvitamin D screening, 80 adults with vitamin D 
deficiency/insufficiency for the main study, 40 adults for treatment 
group and 40 adults for sham controls 
 
Intervention: 
The study treatment is a weekly exposure to the Solius 
Photobiological System, which emits Ultraviolet B (UVB) Radiation. 
This will be accomplished with an established dose of UVB radiation 
for 16 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 concentrations of 25-hydroxyvitamin D 
[25(OH)D] in vitamin D deficient/ insufficient adults of various skin 
types  
 
Design/Methodology: 
We will conduct a double-blinded randomized clinical trial to 
compare the changes in serum 25-hydroxyvitamin D 
concentrations between subjects who receive (intervention group) 
and do not receive (placebo control group) weekly exposures to 
Ultraviolet B (UVB) Radiation generated by the Solius 
Photobiological System for 16 weeks.  Both groups will be exposed 
to blue/purple light which is turned on when the device is 
activated.  The intervention group that will be exposed to the 
Solius Photobiological System will first undergo an evaluation of 
each individual's sensitivity to the Solius Photobiological System 
using the device titration system for the first 5 weeks.  The control 
group will undergo the same process and will only be exposed to 
the blue/purple light.  After the 5 weeks, the subjects will be 
enrolled in a 16-week study where they will be exposed to an 

 
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amount of time based on their individualized titration evaluation.  
The control group will be exposed for the amount of time based on 
their skin type similar to the intervention group. After finishing the 
16-week intervention, the subjects will be asked to return to the 
study site once a week for 4 weeks for measurement of serum 
concentrations of 25-hydroxyvitamin D.  The control group,  will 
undergo the procedures as the treated group with the exception 
that the Solius Photobiological System will only be turned on to 
emit blue/purple visible radiation. We will enroll approximately 100 
adult subjects will be enrolled for serum 25-hydroxyvitamin D 
screening. We expect to enroll 80 vitamin D-deficient or 
insufficient subjects in this study. They will be randomized to 
receive or not receive the UVB radiation intervention.  Both groups 
will be exposed to the same blue/purple visible light so that the 
study subjects will not know whether they are receiving UVB 
radiation or not since UVB radiation is not visible to the human 
eye.  Serum 25-hydroxyvitamin D concentrations will be measured 
monthly, and the concentrations will be analyzed to compare 
between those who receive and who do not receive the UVB 
radiation intervention for baseline and during the 16-week 
treatment period and the end of the study. We expect that the 
serum levels of 25(OH)D will increase by more than ten ng/ml 
after 16 weeks of intervention in the treatment group compared to 
control group. Subjects converted from vitamin D 
deficient/insufficient to insufficient/sufficient is considered a 
minimum clinical important difference (MCID). We expect at least 
70% of vitamin D deficient/insufficient subjects in the treatment 
group to convert to insufficient/ sufficient. 
Also, because of seasonal variations and other confounders, we 
expect a maximum 30% of the subjects to convert to 
insufficient/sufficient in sham control group. 
Total Study Duration: 
12 months 
Subject Participation Duration: 26 weeks including one week for screening, 5 weeks for titration, 16 
weeks for treatment and 4 weeks for post-intervention follow up 
 
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 

 
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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 
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 

 
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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.  
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. 

 
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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) (see 
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 
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  
 
The FDA has required that Solius complete a clinical study with statistical significance to demonstrate 
that the Solius device can safely treat vitamin D insufficiency or deficiency. 
 
 

 
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4 
Objectives 
 
4.1 
Study endpoint 
 
The endpoint is to improve vitamin D status in the treatment group compared to sham controls. We 
expect at least 70% of vitamin D deficient/insufficient subjects in the treatment group to convert to 
insufficient/ sufficient. Also, because of seasonal variations and other confounders, we expect maximum 
30% of subject convert to insufficient/sufficient in sham control group. 
 
Study Outcome Measures 
 
Improvement of serum concentrations of 25(OH)D will be measured by 25(OH)D analysis at 
baseline, each month and the end of the study.  Serum 25(OH)D levels will be determined using 
the Liquid Chromatography with tandem mass spectrometry (LC/MS/MS) method. 
 
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 all subjects (case and control) monthly at various stages 
throughout the 5-week titration and 16-week intervention. Blood samples will be obtained once 
a week for 4 weeks after the 16-week intervention. Baseline samples will be obtained 
immediately preceding the first UVB exposure. Blood samples will be sent to the Quest 
Diagnostics for determining the serum 25(OH)D levels. An additional tube of blood will be 
collected for future study at week 1, week 5, week 13, week 21 and week 25. 
 
 

 
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5 
Study Design 
 
This is a double-blinded sham control clinical trial seeking to determine the safety and efficacy of the 
Solius Photobiologic System in increasing the serum concentrations of 25(OH)D in a vitamin D 
deficient/insufficient adult population. We will make our best effort to recruit individuals with all 
Fitzpatrick skin types as requested by the FDA. The study will be conducted at Boston University after it 
is approved by Boston University’s Institutional Review Board.  
 
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 80 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 
Medical Center’s clinical laboratory for local Quest diagnostic 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 

 
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below 30 ng/ml. Thus, we expect to enroll approximately 100 subjects with different group skin types to 
enroll 80 vitamin D deficient or insufficient subjects in this study. The research coordinator will be 
responsible for randomization and allocation. Thus, the study will be blinded to other members of the 
research team.  Solius and the PI will have no contact with the participants. Subjects will be selected to 
or not to receive the UVB intervention (40 subjects in the treatment group and 40 subjects in the control 
group) (Figure 1). Two study groups will be matched by age, sex, BMI, and skin type by stratified 
randomization.  
The device will have a strip of blue/purple colored LEDs installed inside the device. For users that are 
defined in the treatment group, both UVB lamps and blue/purple colored LEDs will turn on during the 
treatment. For users that are defined in the control group, they will go through the same pre-treatment 
workflow. However, when the user hits start treatment program in the device, only the blue/purple 
LEDs will turn on instead of the UV lamps, which emit radiation that is not visible to the naked eye. 
 
Blood samples that will be obtained at the screening visit will be sent to either BMC’s clinical laboratory 
or a local Quest laboratory for a 24 hour turnaround to determine eligibility of each participant. All 
blood samples collected monthly during the intervention and weekly after the intervention will be sent 
to Quest Diagnostics for measurement of serum concentrations of 25(OH)D by liquid chromatography 
with tandem mass spectrometry analysis as requested as requested by the FDA.  The study design is 
summarized in Figure 1 and Table 2. As shown in the Table 2, blood samples will be collected at the 
screening visit, during the intervention period (week 1, week 5, week 9, week 13, week 17 and week 21). 
As requested by the FDA, we will also obtain blood sample after the intervention (week 22 – 25). We will 
collect an additional tube of blood for future study at week 1, week 5, week 13, week 21 and week 25. 
 

 
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Figure 1. Summary of protocol: Evaluating the effect of the Solius Photobiologic System in improving 
vitamin status in adults  
        
 
 

 
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Table 2. Outcomes measurement at each time point of the study for both study groups 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activity 
Screening 
Titration  
Intervention  
Wk  
1 
Wk  
2 
Wk  
3 
Wk  
4 
Wk  
5 
Wk  
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15 
Wk 
16 
Wk 
17 
Wk 
18 
Wk 
19 
Wk 
20 
Wk 
21 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exc
lusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographi
cs/ 
Skin typing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
UVB 
Exposure/sh
am exposure 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
25(OH)D  
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Additional 
blood  
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Sun 
exposure/ 
Vit. D food 
checklist 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse 
Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Activity 
Post-intervention 
Wk 
22 
Wk 
23 
Wk 
24 
Wk 
25 
Informed 
Consent 
 
 
 
 
Inclusion/Exc
lusion 
 
 
 
 
Medical 
History 
 
 
 
 
Demographi
cs/ 
Skin typing 
 
 
 
 
UVB 
Exposure/sh
am exposure 
 
 
 
 
25(OH)D  
X 
X 
X 
X 
 
Sun 
exposure/ 
Vit. D food 
checklist 
 
 
 
X 
Concomitant 
Medications 
X 
X 
X 
X 
Adverse 
Events 
X 
X 
X 
X 

 
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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   
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 
subject in the device before each treatment. The device software will require that the subject physically 
obtained the eye protection from the dispenser in the device before the device can be turned on to emit 
the UVB light.  An additional safety feature of the device is the height of the emitting lens is 51”. Testing 
conducted by 3rd party showed that there is almost 0 UV output at 56” from the floor. Thus, little or no 
radiation is emitted above the height of 5 feet and therefore the face and eyes will not be exposed to 
the UVB light if for some reason the subject does physically place the eye protection shield over his/her 
eyes.  This is demonstrated in the enclosed picture of the device along with its other features. 

 
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The UV light panel height is 51 inches. 
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% 
each step until a maximum erythemally weighted dose of 34.88 mJ/cm2 – 109.33 mJ/cm2 (depending 
on skin type). If the subject shows a skin reaction i.e erythema, the dose will be reduced to 60% of the 
dose that caused the skin reaction/erythema.  
 
The subject’s dosage will be administered under conditions of full-body exposure except the face (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 16 weeks. At each visit, the subject will report adverse events and any skin 
changes.   
 
The PI will be available to the study staff member to answer any questions or concerns from potential 
subjects prior to consenting. 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 immediately if any side effects do occur. 
The PI will advise the study staff who have received the information from the subject as to how this side 
effect should be handled, recorded and reported. After the determination, all samples will be 
de-identified.  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 (years to decades) vitamin D deficiency and 
insufficiency can lead to bone loss resulting in increased risk of fracture later in life.  Chronic vitamin D 

 
Page 15 of 28 
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deficiency can also cause a mineralization defect of the skeleton resulting in osteomalacia.  Short term 
(6 months) vitamin D deficiency and insufficiency is not associated with significant bone loss or 
osteomalacia. Therefore, the participants, especially those who are in the sham treatment group, are at 
no increased risk for fracture or osteomalacia.  At the termination of this study those participants who 
were in the sham group 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. All participants in the study will know that they are 
vitamin D deficient/ insufficient because that will be a requirement for being enrolled in the study. The 
control group will only know their vitamin D status and will receive no additional benefit for 
participating in the study. The group exposed to the Solius Photobiological System’s UVB light may 
improve their vitamin D status because the UVB emitting lamps are designed for producing vitamin D in 
the skin similar to sunlight. Results from this study will provide scientific knowledge regarding this 
devices ability to produce vitamin D and improve vitamin D status in people with vitamin D deficiency 
such as subjects with fat-malabsorption syndromes. All subjects will be evaluated for vitamin D 
deficiency/insufficiency at the end of study and subjects with vitamin D deficiency/insufficiency will be 
advised to take a vitamin D supplement along the guidelines recommended by the Endocrine Society 
Practice Guidelines on Vitamin D.  Alternatively, if they do not wish to take a supplement and would like 
a prescription for vitamin D we will contact their primary care doctor and inform them of their vitamin D 
status so that they can prescribe the appropriate vitamin D treatment as recommended by the 
Endocrine Society’s Practice Guidelines on Vitamin D.   
 
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.  
 
 
 
 
 
 
Study 
group/activity 
Post-intervention 
Total 
Wk 
22 
Wk 
23 
Wk 
24 
Wk 
25 
Activity  
(both treatment 
group and sham 
control group) 
BD 
BD 
BD 
BD 
$1550 
Up to 
2,330 
Compensation 
$50 
$50 
$50 
$250 
Transportation 
cost up to 
PV 
or 
up 
PV 
or 
up 
PV 
or 
up 
PV or 
up to 
$30 
Up to 
$780 

 
Page 16 of 28 
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Note: BD: Blood draw; UV: Ultraviolet B radiation exposure or sham control 
Blood samples will be collected after each UV exposure.  
 
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  
to 
$30 
to 
$30 
to 
$30 
Study 
group/activity 
Screening 
visit 
Titration 
Intervention  
Wk  
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk  
6 
Wk 
7 
Wk 
8 
Wk 
9 
Wk 
10 
Wk 
11 
Wk 
12 
Wk 
13 
Wk 
14 
Wk 
15 
Wk 
16 
Wk 
17 
Wk 
18 
Wk 
19 
Wk 
20 
Wk 
21 
Activity  
(both treatment 
group and sham 
control group) 
Screening 
Consent 
BD 
UV 
UV 
UV 
UV 
UV 
BD 
UV 
 
UV 
UV 
UV 
BD 
UV 
 
UV 
UV 
UV 
BD 
UV 
UV 
UV 
UV 
BD 
UV 
UV 
UV 
UV 
BD 
Compensation 
$100 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
$50 
Transportation 
cost  up to 
PV or up 
to $30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 
PV 
or 
up 
to 
$30 

 
Page 17 of 28 
\\DC - 760509/000001 - 15602675 v1   
 
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.   
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 
 
The treatment group (n=40) will be exposed to the Solius Photobiological System, and the control group 
(n=40) will receive the same procedure with only the blue/purple LEDs. 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 blue/purple LEDs installed inside the light towers. For users that are 
defined in the treatment group, both UV lamps and purple LED will turn on during the treatment. For 
users that are defined in the control group, they will go through the same pre-treatment workflow. 
However, when the user hits start treatment, only blue/purple LEDs will turn.  The times that the control 
subjects will be in the sham operational device mode for the titration phase and 16-week treatment 
phase will be the same as those in the intervention UVB device mode based on skin type. 
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 concentration 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 16 

 
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weeks to observe the effect on 25(OH)D serum concentration. Serum 25(OH)D concentration will be 
monitored until 4 weeks after the intervention.  
 
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. This screen is anonymous and 
no answers will be recorded. During the preliminary anonymous screening telephone call, the subject 
will be asked about their medical history and inclusion/exclusion criteria. None of the answers or 
identifiable information will be recorded. Completion of the preliminary anonymous screening will be 
documented in the study binder. Once the subjects are determined to be eligible, they will 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 process that they have prior to signing 
the consent form. This consent form will also allow us to perform a 25(OH)D blood screen, collect urine 
samples,  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.  
 
We plan to use sham control with doing a modification on instrument hardware and software. The 
research coordinator will be responsible for randomization and allocation. Thus, the study will be 
blinded to other members of the research team. Approximately 100 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 100 subjects with different group skin types to enroll 80 vitamin D deficient or 
insufficient subjects in this study. They will be randomized to receive or not to receive the UVB 
intervention (40 subjects in the treatment group and 40 subjects in the control group) (Figure 1). The 
device will have a strip of colored LED installed inside the light towers. For users that are defined in the 
treatment group, both UV lamps and colored LED will turn on during the treatment. For users that are 
defined in the control group, they will go through the same pre-treatment workflow. However, when 
the user hits start treatment, only blue/purple LEDs will turn on instead of the UV lamps, which are 
invisible. 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 exactly the same for active and control 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 blue/purple light will 
be emitted from the same emitting window as the UV lamps.  The subjects will not know if they are 
being actively treated or not and we will make the experience for both be virtually the same. The 
research coordinator who sets up the device will know only which arm the subject is assigned to (arm A 
or B) but will not know which arm is the treatment or control. 
 

 
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Blood samples that will be obtained from all participants at the screening visit will be sent to either 
BMC’s clinical laboratory or a local Quest laboratory for a 24 hour turnaround to determine eligibility of 
each participant. All blood samples collected monthly during the intervention and weekly after the 
intervention will be sent to Quest Diagnostics for measurement of serum concentrations of 25(OH)D by 
liquid chromatography with tandem mass spectrometry analysis.  The study design is summarized in 
Figure 1 and Table 2. As shown in the Table 2, blood samples will be collected at the screening visit, 
during the intervention period (week 1, week 5, week 9, week 13, week 17, week 21) and after the 
intervention (week 22 – 25). We will collect an additional tube of blood for future study at week 1, week 
5, week 13, week 21 and week 25.  
 
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 or to expose the control group for this same amount of 
time in the sham operated device for their skin type.  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 16-week course of 
SoliusONE treatment or sham 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 or LED 
visible blue/purple light. Each subject will be asked to wear a swimsuit, swimming trunks (for males) or 
bikini (for females) while being exposed to UVB or sham LED light 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 
radiation and blue/purple light  or the sham group will be exposed to only the blue/purple 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 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 (cases and controls) at the screening visit and monthly 
throughout the 16 weeks of the study duration (weeks 1, 5, 9, 13, 17, 21), and weekly after the 16-week 
intervention for 4 weeks (week 22 – 25). Blood samples will be sent to Quest Diagnostics for 
determining the serum 25(OH)D levels. The study design summarized in Figure 1 and Table 2 
 
If a subject needs to end his/her regiment 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 12 months to complete 16-week treatment for case group. As 
discussed earlier the study subject’s involvement will last 26 weeks from screening to completion 
include one week for screening, 5 weeks for titration, 16 weeks for treatment and 4 weeks of post-
treatment serum 25(OH)D monitoring.  

 
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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.  
 
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. 
 

 
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10.2 Safety Review 
 
Dr. Shirvani or Dr. Charoenngam will interview the subjects in the intervention and sham groups before 
their next exposure each week for any adverse events including erythema or any other skin reactions. 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.  
 
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.  
 
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 
 
 
10.3 Reporting Plans 

 
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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 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 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. 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. 
 

 
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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 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 
The endpoint is the difference in vitamin D insufficiency/sufficiency prevalence between the treatment 
and the control group use at 16 weeks of follow-up. The subject will have at least one serum 25(OH)D 

 
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evaluation within 16 weeks, and at least one phototherapy session in the 16 weeks follow up. The 
protocol includes a sample size calculation, which allowed for a loss to follow-up of 15%. 
Statistical analysis will be performed using SPSS Statistics, version 25 (IBM Corporation). Age, sex, BMI, 
and Fitzpatrick skin type will be matched in two study groups. Two-sided P < .05 will be considered 
significant. All models will be developed according to the intention-to-treat principle. A supportive 
analysis will also be conducted on the per-protocol (PP) population. 
The biological and clinical characteristics at enrolment will be presented, and all variables for the 
participants in the treatment and control groups will be compared at each follow-up using Fisher’s exact 
test for categorical variables and a Mann–Whitney U test for continuous variables. For intergroup 
differences, 95% CIs will be also calculated. The endpoint, the proportion of subjects converting from 
vitamin D deficiency/insufficiency to vitamin D insufficiency/sufficiency at 16 weeks will be compared 
between groups using Fisher’s exact test and logistic regression adjusting for skin types. Secondary 
analysis will be involved a comparison of changing in serum levels of 25(OH)D between groups using a 
Mann–Whitney U test and linear regression adjusting for skin types. A linear mixed model will be used 
to examine the relationship between phototherapy and serum 25(OH)D3 at different time points, 
adjusting for the baseline values and correlation of outcomes within individuals and season. 
12.1 Study Hypotheses 
 
We suspect that with the incorporation of a 16-week phototherapy regiment, at least 70% of vitamin D 
deficient/insufficient subjects in the treatment group will convert to insufficient/ sufficient. Also, 
because of seasonal variations and other confounders, we expect a maximum 30% of the subjects to 
convert to insufficient/sufficient in sham control. In particular, we expect individuals with Fitzpatrick 
Type I and II skin to show the greatest response to phototherapy.  
 
 
 
12.2 Sample Size Determination 
 
The endpoint of this study is to compare the improvement of vitamin D status between treatment group 
and the controls. 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 after 8 weeks (13). We would expect that to increase the serum 25(OH)D level by 10 ng/mL 
(SD=5ng/ml), after 16 weeks based on a previous study (13) as well as an earlier pilot study that was 
completed by Solius.   
The endpoint is to improve vitamin D status in the treatment group compared to sham controls. We 
expect that the serum levels of 25(OH)D will increase more than 10 ng/ml (SD=5ng/ml) after 16 
weeks of intervention in the treatment group compared to controls.  Subjects converted from vitamin 
D deficient/insufficient to insufficient/sufficient is considered a minimum clinical important difference 
(MCID). We expect at least 70% of vitamin D deficient/insufficient subjects in the treatment group to 
convert to insufficient/ sufficient. Also, because of seasonal variations and other confounders, we 
expect maximum 30% of subject convert to insufficient/sufficient in sham control. 
With the desired power of 80% and significance level (α) of 0.01, the sample size in each group is 35. 
 
Approximately 100 adult subjects with 5 skin types group (I, II, III, IV and V/ VI) will be enrolled for 
vitamin D deficiency/ insufficiency screening. We expect that at least 80% of the population in the 

 
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Boston area has a level of 25(OH)D below 30 ng/ml. Thus, we will enroll 100 subjects with different skin 
types to enroll 80 vitamin D deficient or insufficient subjects in this study. We plan to match treatment 
and control group for age, sex, BMI and skin type by stratified random sampling (40 subjects in each 
group). In our experience, the rate of screen failure and subject dropout is 10-15%. Then, we expect to 
have at least 35 subjects per each group. 
 
Parameters 
Value 
Conversion of the subjects from vitamin D deficient to vitamin D 
insufficient/sufficient or vitamin D insufficient to vitamin D sufficient in the 
treatment group after 16 weeks (P1) 
70% 
Conversion of the subjects from vitamin D deficient to vitamin D 
insufficient/sufficient or vitamin D insufficient to vitamin D sufficient in the control 
group after 16 weeks (P2) 
30% 
Significant level 
0.01 
Power 
80% 
 
 
 
 
The research coordinator will be responsible for randomization and allocation. Thus, the study will be 
blinded to other members of the research team. We expect that the serum levels of 25(OH)D will 
increase by at least 10 ng/ml in the treatment group compared to the control group after 16 weeks UV 
exposure in a linear fashion. We will do an assessment every four weeks, expecting that there will be a 
minimum of 2.5 ng/ml increase in the serum 25(OH)D. We will conduct the blinded interim analyses to 
re-assess the planned sample size after thirty five subjects in each group have completed four weeks of 

 
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intervention  by an independent statistician. The sample size adjustment will be made to ensure the 
appropriate power to determine the effect of UV exposure on vitamin D synthesis.  
 
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). 
 
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 
 
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5. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies 
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