A Pilot Feasibility Study Comparing a Novel Phototherapy Kiosk to Supplementation to Promote Vitamin D Sufficiency
Phase: NA
Conditions: Hypovitaminosis D
Sponsor: Madigan Army Medical Center

 
 
 
 
 
 
 
 
 
 
 
A PILOT FEASIBILITY STUDY COMPARING A NOVEL PHOTOTHERAPY KIOSK TO SUPPLEMENTATION  
TO PROMOTE VITAMIN D SUFFICIENCY 
PROTOCOL # 217121 
 
NCT04556136 
 
27 JUNE 2017 
 
  
  
  
 
 
 

 
                                                                                                                                                       
 
 
Page 1 of 15 
Title Page 
 
Study Title: A Pilot Feasibility Study Comparing a Novel Phototherapy Kiosk to Supplementation to 
Promote Vitamin D Sufficiency 
 
Name of Product Tested: Solius, Photobiologic therapy kiosk 
 
Indication Studied: Maintenance or repletion of serum 25(OH)D status 
 
Study Description:  This pilot feasibility study was designed to provide validation of the isolation of narrow 
spectrum ultraviolet B (UVB) rays delivered in a standing kiosk. A measured dose was administered under 
conditions of full body exposure every other week for 10 weeks. The stimulation of cutaneous vitamin D 
and subsequent 25(OH)D production from phototherapy was compared to the effect of an IOM 
determined RDA dose of 600 IU vitamin D3 supplement daily for 10 weeks. The primary outcome was 
serum 25(OH)D level. 
 
Sponsor: BeneSol, Inc. dba SOLIUS 
 
Protocol: Non-inferiority, feasibility, randomized, controlled trial with Institutional Review Board approval 
as a minimal risk human use protocol. 
 
Phase of Development: Premarket 
 
Study Initiation Date: 21 August 2017 
 
Study Completion Date: 11 March 2019 
 
Name of principal or coordinating investigator: Mary S. McCarthy, PhD, RN. Madigan Army Medical 
Center 
 
 
DCP Statement: This study was performed in compliance with ICH Good Clinical Practice (GCP) including 
the archiving of essential documents. 
 
 
 
 

 
                                                                                                                                                       
 
 
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1 List of Abbreviations & Definition of Terms 
 
AD 
Active duty 
BIA 
Bioelectrical impedance analysis 
BMI 
Body mass index 
BMR 
Basal metabolic rate 
CAP 
College of American Pathologists 
CG 
Comparison group 
DXA 
Dual energy xray absorptiometry 
FST 
Fitzpatrick skin type 
IQR 
Interquartile range 
IRB 
Institutional Review Board 
JBLM 
Joint Base Lewis-McChord 
MAMC 
Madigan Army Medical Center 
MCAR 
Missing completely at random 
Mdn(mdn) 
Median 
Nm 
Nanometer 
 
Ng: 
Nanogram 
SM 
Service member 
SPK 
Standing phototherapy kiosk 
TG 
Treatment group 
 
 

 
                                                                                                                                                       
 
 
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2 Ethics and Regulatory Approval 
2.1 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) Approval 
The study protocol and all its amendments were reviewed and approved by the IRB as detailed in 
table one below. 
 
IRB Name 
 
Regional Health Command – 
Pacific Institutional Review Board 
Principal Investigator Mary S. McCarthy, PhD, RN. MAMC 
Date of approval of the final protocol 27 June 2017 
Date of approval of amendment 1 5 October 2017 
Date of approval of amendment 2 9 March 2018 
Date of approval of amendment 3 11 May 2018 
 
The study was performed in compliance with FDA 21 CFR 812. Since the product under 
investigation is low risk, IRB approval is sufficient.  
2.2 
Ethical Conduct of the Study 
The study was performed in accordance with the current version of the declaration of Helsinki 
(52nd WMA General Assembly, Edinburgh, Scotland, October 2000). The trial was conducted in 
agreement with the International Conference on Harmonization (ICH) guidelines on Good Clinical 
Practice (GCP). 
2.3 
Patient Information and Consent  
All patients provided written informed consent to participate in the study prior to being screened. 
The patient was given a copy of the signed consent form for their personal records. The original 
copy of the informed consent is kept in document control along with this test report. A sample of 
the consent form can be found along with the IRB-approved study protocol. 
 
 
 
 

 
                                                                                                                                                       
 
 
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3 Investigators and Study Administrative Structure 
The table below shows the principal study personnel involved in the study. 
 
Title  Name and Affiliation 
Principal Investigator Mary S. McCarthy, PhD, RN, FAAN. MAMC 
Sponsor BeneSol, Inc. dba SOLIUS 
Project Manager Evelyn Elshaw, MS, RD, LD. MAMC 
Clinical Research Associate(s) Barbara Szekely, BSN, RN. MAMC 
Biostatistician Thomas A Beltran, MA.  (Contractor) 
 
4 Introduction 
Low vitamin D status is common in individuals who regularly perform extreme physical exertion, 
particularly in combination with periods of psychological stress, inadequate nutrition, and sleep 
disruption.1 This places military personnel in a high risk category with significant negative consequences 
to musculoskeletal, immune, and mental health, and thus, resilience. The large scope of this problem 
demands a multi-phased approach beginning with a self-care, easy access, safe biomedical device 
intended to stimulate cutaneous production of vitamin D. The pilot, or demonstration phase, involved 
installment of a standing phototherapy kiosk in an outpatient setting where we enrolled Active Duty 
(AD) and retired Service Members (SM), adult beneficiaries, and DA civilians to test the acceptability and 
feasibility of this health promotion concept. We anticipated that the phototherapy kiosk would be an 
inexpensive, convenient, and effective way to maintain or raise 25(OH)D levels to sustain Warfighter and 
beneficiary resilience.   
 
Endogenous production of vitamin D comes from sun exposure, however concerns of skin cancer and 
heat injuries limits recommendations for even a safe level of exposure. The only alternative has been 
consumption of vitamin D supplements, yet there is a paucity of evidence for how often, how much, and 
for how long one should consume supplements. Unlike endogenous vitamin D, research shows that 
supplements do not bind completely to vitamin D binding protein and are not regulated in the body to 
prevent overdose.32-35 Fat malabsorption conditions (cystic fibrosis, Crohn’s disease, celiac, liver disease, 
etc.) can reduce the ability to absorb fat soluble vitamin D supplements yet endogenous vitamin D 
production from UVB light is uninhibited.2,36-40 UVB radiation with a wavelength of 290-320 nm 
penetrates the exposed skin and converts cutaneous 7-dehydrocholesterol to pre-vitamin D3, which in 
turn becomes vitamin D3. Maximal immune system response occurs at a peak of 300 nm and vitamin D3 
production at a peak of 298 nm.3 Sunlight exposure provides 80-100% of the body’s vitamin D 
requirements. Factors that influence UVB exposure and vitamin D synthesis include season, time of day, 
length of day, cloud cover, smog, skin melanin content, and sunscreen. However, a simple “prescription” 
for midday sun exposure under a cloudless sky with 90% skin exposure and no sunscreen in a non-urban, 
minimally polluted environment is a challenge for almost every American, and even more so for Service 
Members.  
 
The current standard of care is 600 IUs oral vitamin D daily, which is the RDA established by the Institute 
of Medicine (IOM) who identified clinically significant levels of circulating 25(OH)D to be 20 ng/mL. The 
RDA for vitamin D represents a daily intake sufficient to maintain bone health and normal calcium 

 
                                                                                                                                                       
 
 
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metabolism in 97.5% of the population.20  While debate surrounds a sufficient range for 25(OH)D, there 
does seem to be a general acceptance that the optimum range is between 30 – 60 ng/mL.5-7  The human 
body uses sunlight as the primary source of vitamin D and produces large quantities efficiently with 
limited UVB exposure.12-15 Therefore, a rational way to determine the optimum vitamin D range is by 
studying natural cutaneous vitamin D synthesis. It has been demonstrated that a single session of full 
body exposure to solar radiation can produce a time-released equivalent of approximately 10,000 IU of 
oral vitamin D.16 A safe upper limit for vitamin D is related to oral intake only. Cutaneous vitamin D 
production is automatically regulated by a photochemical reaction and pigmentation, preventing 
toxicity.17-19 Consequently, hypervitaminosis D is not possible when the only vitamin D source is skin 
production following exposure to UVB light. For all these reasons, an innovative alternative to address 
low vitamin D status in adults, Warfighters included, is needed. 
5 Study Objectives 
The specific aims for this project were: 
1. Determine acceptability and feasibility of a standing phototherapy kiosk designed as a self-
care intervention for AD and retired service members, beneficiaries, and DA civilians; 
2. Demonstrate that narrow spectrum UVB delivered by the SPK is at least equivalent to D3 oral 
intake to raise or maintain serum 25(OH)D levels over a 10-week intervention period; 
3. Examine the relationship of demographic variables, including gender, age, body mass index, 
body fat, ethnicity, and sun exposure to serum 25(OH)D levels in both groups. 
6 Investigational Plan 
6.1 
Overall Study Design and Plan 
This non-inferiority study used a prospective, longitudinal, randomized design with repeated 
measures to address vitamin D sufficiency in AD, retiree, beneficiary, and DA civilian populations. 
It is important and necessary to conduct this study with adult humans, military personnel in 
particular, to determine acceptability and feasibility of this phototherapy kiosk as an addition to 
existing Warfighter resources to promote health and resilience. Following Madigan Army Medical 
Center (MAMC) Institutional Review Board Human Subjects and Ethics approval, the SPK will be 
installed in a location approved by the Radiation Safety Officer, the study team will be hired, and 
recruitment will begin for an anticipated 12-month project period. Approximately 120 volunteers 
will be approached from MAMC and Joint Base Lewis-McChord (JBLM), a large joint base in the 
Pacific Northwest, where over 25,000 Soldiers and Airmen train every day and regional 
beneficiaries’ number ~98,000. Recruiting efforts will attempt to capture a representative sample 
of the population including both genders, diverse ethnicities, and a range of age (18-70 years) and 
body mass index (BMI), who have no contraindication for UVB exposure or oral vitamin D 
supplementation. In addition to walk-in volunteers, the research team will attend the JBLM 
Newcomer’s Orientation. Using a computer-generated block design, volunteers will be 
randomized to one of two groups by the research pharmacist; 1) oral vitamin D supplementation, 
or 2) standing phototherapy kiosk with UVB exposure, for a 10-week period.  
 
Comparison Group (CG) – Supplement 
A MAMC research pharmacist will dispense a 70-day supply of the vitamin D3 600 IU oral 
supplement to subjects assigned to this group. The Project Director will work with the pharmacist 
to coordinate pick-up of supplement bottles for subjects or optimal in-person dispensing times. 
 

 
                                                                                                                                                       
 
 
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Treatment Group (TG) – Phototherapy 
The Project Director provides oversight for the phototherapy treatment. The kiosk will deliver the 
UVB dose under supervised conditions over a 1 – 10 minute interval based on the Fitzpatrick skin 
type with the subject wearing minimal or no clothing, preferably no more than a bathing suit, and 
protective eye-wear. The experience in the SPK was designed to be comfortable and user-friendly. 
 
All eligible adult volunteers will be enrolled regardless of their baseline 25(OH)D level as it is 
important in this non-inferiority study to show there is no potential for harm from phototherapy, 
even if the baseline 25(OH)D level is above 30 ng/mL. If the goal is to develop a self-care kiosk, 
individuals will not have the ability to check their serum vitamin D status prior to use. We also 
want to learn the trajectory of vitamin D absorption and availability over a 3-4-month period in 
order to make evidence-based therapeutic recommendations. It is not possible to blind the 
subjects or research team to the group assignment given the two comparators.  
 
Serum levels of 25(OH)D, calcium, and parathyroid hormone are drawn at baseline (T0), 
immediately following the intervention at 10 weeks (T6); at 14 weeks (T8), 25(OH)D is drawn to 
document sustainment of treatment effect. Remuneration in the form of $20 Amazon gift cards is 
provided to all volunteers after the baseline and final scheduled blood draw (as allowed by DoD 
Instruction 3216.02 Dated November 8, 2011).  
 
A survey shall be completed at T1 and reviewed with participants again at the 10-week visit to 
capture relevant demographic, medical history, sun exposure, travel, daily activities, and dietary 
data. Active duty SMs shall report the number of days on profile (activity restriction) for the 
previous three months, at T1 and T6. A Device Usability Scale will be administered to the kiosk 
group participants upon protocol completion to address acceptability and feasibility of the 
treatment. With the assistance of a biostatistician, we will analyze data using repeated measures 
analysis of variance adjusting for significant covariates such as 25(OH)D level at baseline. Logistic 
regression analyses are used to predict outcomes and explain the interrelationships among 
variables, i.e. age, gender, BMI, body fat, ethnicity, and sun exposure relationship to 25(OH)D 
serum levels. 
6.2 
Discussion of the Study Design, Including the Choice of Control Groups 
The objective of this non-inferiority study is to demonstrate the ability of the phototherapy kiosk 
to safely administer UVB radiation to participants with sufficient or insufficient levels of 25(OH)D 
and achieve comparable levels of serum 25(OH)D in a similar population of adults randomized to 
receive the RDA of 600 IU vitamin D oral supplementation once daily. As an experimental device, it 
is important to evaluate its equivalence to standard of care in the maintenance of sufficient levels 
of vitamin D in adults with all skin types between 18 and 69 years of age. In this study the 
supplement group (CG) was used as an active control. 
6.3 
Selection of Study Population 
Inclusion and exclusion criteria are identical for both groups, supplementation (CG) and phototherapy 
(TG). 
6.3.1 
Inclusion Criteria 
• 
Adults, age 18 - 69 years 
• 
Ability to read and understand English 
• 
Subjectively in good health 

 
                                                                                                                                                       
 
 
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• 
Able to stand without assistance for ~10 minutes 
6.3.2 
Exclusion Criteria 
• 
Any volunteer with relocation, deployment, or release from active duty in the next 4 
months 
• 
Pregnant, or currently breastfeeding, females 
• 
Anyone with chronic health problems (e.g. kidney disease, liver disease, intestinal 
malabsorption) 
• 
Any volunteer currently taking vitamin D supplementation  
• 
Taking medications for an endocrine disorder, such as Synthroid or oral hypoglycemic 
agents   
• 
Sarcoidosis 
• 
Medications having a high potential for interaction with vitamin D: 
o anti-seizure medications, cyclosporine, indinavir (Crixivan)  
• 
Adults diagnosed with light allergies: 
o Actinic prurigo, Polymorphous light eruption, Solar urticaria 
• 
Adults diagnosed with light sensitivities: 
o Protoporphyria, Photodermatitis, Xeroderma pigmentosum, Lupus erythematosus, 
Actinic dermatitis, UV-sensitive syndrome  
 
6.3.3 
Removal of Patients from Therapy or Assessment 
Participants enrolled in the study are free to withdraw at any time without repercussions; the 
study team requested to be informed in writing of their decision to withdraw. 
 
Volunteers are reminded that the Principal Investigator of the research study may terminate 
their participation in the research study at any time if she determined this to be in their best 
interest, if they are unable to comply with the procedures required, or if they no longer meet 
eligibility criteria. 
 
6.4 
Treatments 
6.4.1 
Treatments Administered 
Comparison Group - Supplement 
Volunteers assigned to this group are provided with a 10-week supply (70 pills) of a vitamin D3 
supplement. Consented participants are instructed to take one 600 IU pill by mouth each day 
for ten weeks. They are instructed to take this with a meal. This dose is the RDA for adults 
between 18 and 69 years old according to the Institute of Medicine Committee to Review 
Dietary Reference Intakes for Vitamin D and Calcium.20 
 
 
Treatment Group - Phototherapy  
Volunteers assigned to this group are administered phototherapy treatments once every 
other week, for 10 weeks. The treatment usually lasts no more than 10 minutes and is based 
on the Fitzpatrick skin type classification tool19 which is self-assessed via the computer touch 
screen in the kiosk.  
 
 

 
                                                                                                                                                       
 
 
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6.4.2 
Identity Investigational Product 
The Solius phototherapy device (SOLIUSOne, Serial# 00102) is intended for use in the 
stimulation of endogenous vitamin D. Solius is a freestanding booth designed to deliver a 
small amount of targeted UVB with an interactive user interface and cloud-based software 
that enables patient self-care. The treatment delivery mechanism uses a metal halide lamp 
with a series of filters and a lens to optimize full-body exposure to the narrow spectrum (293 – 
303nm) of UVB light most efficient at producing vitamin D3. The device uses software to 
identify patients, establish individual skin types and determine dosage. The system has been 
designed to manage exposure time and frequency and deliver 60% of a skin-type-adjusted 
Minimal Erythemal Dose (MED). The expected result for users is a rise in blood levels of 
25(OH)D via the endogenous pathway.13 
 
6.4.3 
Method of Assigning Patients to Treatment Groups 
A computer-generated block design will be created by an onsite biostatistician and used by 
the research pharmacist to randomize participants. Upon meeting the inclusion criteria, the 
pharmacist will be notified of the new participant and she will relay the assigned group to the 
team. The study team will have had no knowledge of the group assignment in advance.     
 
6.4.4 
Selection of Doses in the Study 
Comparison Group - Oral Supplement Dosing 
For this non-inferiority study, the logical choice for a comparison arm was the Recommended 
Daily Allowance (RDA) of 600 IU vitamin D for adults in the age range of 18-70 years old. The 
RDA was established by the Institute of Medicine (IOM) who identified clinically significant 
levels of circulating 25(OH)D (20 ng/mL) and then estimated the amount of dietary vitamin D 
required to reach this circulating level with minimal sunlight exposure. The RDA for vitamin D 
represents a daily intake sufficient to maintain bone health and normal calcium metabolism in 
97.5% the population.20  
Table 1. Study Summary 
Phase 
Initial 
(T) 
Time 1 
(T+1wk) 
Time 2 (T+3wk) 
Time 3 (T+5wk) 
Time 4 (T+7wk) 
Time 5 (T+9wk) 
Time 6 (T+11wk) 
Time 7 
(T+15wk) 
Screening 
X 
 
 
 
Informed Consent 
X 
 
 
 
Submit Blood Tests 
X 
 
X (Time 6) 
X 
Randomization 
X 
 
 
 
Demographics and Surveys 
 
X 
X (Time 6) 
 
Inbody 
 
X 
 
 
Treatment -Phototherapy 
(every other week x6) 
 
X 
X (Time 6 = Final Exposure) 
 
Device Usability Scale - 
Phototherapy 
 
 
X (Time 6) 
 
Treatment -Vit D Supplement 
(daily for 10 weeks) 
 
X 
X 
 

 
                                                                                                                                                       
 
 
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Treatment Group - Phototherapy Dosing 
All patients shall be dosed at 0.6 MED at a distance of 12” from the light source for all 
treatments. This is consistent with dosing demonstrated to be effective at raising serum 
25(OH)D without the risk of adverse events. 26, 27 Treatments shall occur on a 14-day interval 
(+/- 24 hours), for a total delivery of 6 doses.  
 
To obtain dose, each participant will self-assess their skin type according to the Fitzpatrick skin 
typing scale using software inside the kiosk. The kiosk will determine the dose per patient, 
based on their answers. Erythemal response to the previous treatment dose is self-assessed. 
In the event erythema is self-reported via the kiosk, the participant’s dose is reduced by the 
system for subsequent treatments. 
 
 
 
6.4.5 
Selection and Timing of Dose for Each Patient 
Comparison Group 
Each participant assigned to the comparison group will be instructed to take one vitamin D3 
pill each day with a meal for 70 days. Participants will also be instructed not to take any 
additional vitamin D supplementation during the study period. This dosing frequency is 
consistent with the RDA recommendation.20 
 
Treatment Group 
Treatments shall occur on a 14-day interval (+/- 24 hours), for a total delivery of 6 doses. Each 
participant is informed of the need for consistency in the time of day for subsequent 
phototherapy treatments and every attempt will be made to ensure the participants return 14 
days after each treatment for 10 weeks. This dosing frequency is consistent with the minimum 
recommended for Solius vitamin D therapy previously shown to be adequate in maintaining 
serum 25(OH)D levels.26, 27   
 
6.4.6 
Blinding 
Due to the nature of the study, it is not possible to blind the subjects or research team to the 
group assignment. 
 
6.4.7 
Prior Concomitant Therapy 
Other medications are allowed except those listed in the exclusion criteria (anti-seizure 
medications, cyclosporine, and idinavir). The research pharmacist will provide expertise for 
establishing screening criteria to eliminate any potential drug-drug or drug-nutrient 
interactions. No attempt will be made to control for sun exposure or dietary intake of vitamin 
D, however, all participants are instructed to refrain from taking any additional supplements 
containing vitamin D. Volunteers will be asked about vitamin D supplementation during 
screening and anyone taking a vitamin D supplement in the previous 2 months will not qualify 
for the study. Both amount of sun exposure and consumption of dietary vitamin D will be 
captured on surveys. Logistic regression analyses will be used to predict outcomes and explain 
the interrelationship among the two variables (i.e. sun exposure relationship to 25(OH)D 
serum levels). 
 
 
 
 

 
                                                                                                                                                       
 
 
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6.4.8 
Adherence 
Comparison Group 
Participants agree to oral administration of 600 IU vitamin D once per day. Participants must 
agree to abstain from ingesting oral vitamin D supplements. Participants must also have blood 
drawn at baseline , day 70, and at day 100.   
 
Treatment Group 
Participants must be exposed once every other week (14 days +/- 24 hours). Participants must 
agree to abstain from ingesting oral vitamin D supplements. Participants must also have blood 
drawn at baseline, day 70, and at day 100.   
 
In this pilot feasibility study, one aim is to evaluate acceptability and adherence.  
 
6.5 
Efficacy and Safety Variables 
6.5.1 Efficacy and Safety Measurements Assessed 
To determine that phototherapy is at least equivalent to D3 oral intake to raise or maintain 
serum 25(OH)D levels over a 10-week intervention period baseline 25(OH)D levels are obtained. 
Blood draws will occur upon enrollment with two follow-up measurements, one at 10 weeks 
and a final level 4 weeks after completing the protocol to evaluate sustainment of the post-
treatment level. Serum concentration of 25(OH)D is the best indicator of vitamin D status as it 
represents cutaneous production and consumption of food and supplements. Serum 25(OH)D 
has a circulating half-life of 15 days.28 Serum 25(OH)D levels do not indicate the amount of 
vitamin D stored in body tissues.10 All blood levels will be obtained by experienced 
phlebotomists in the hospital central laboratory. There will be no standardization of time of day 
for the blood draw. An Endocrine consultant will review all abnormal lab values [(25OH)D, PTH, 
Calcium] and recommended follow-up with the Primary Care Manager, if necessary. 
 
To determine acceptability and feasibility of the standing phototherapy kiosk, a Device Usability 
Scale will be administered to the Kiosk Group upon completion of the study. This 12-item Likert-
type scale was adapted from the Digital Equipment Corporation “System Usability Scale” (1986). 
Questions assessed cleanliness, ease of use, and comfort of the kiosk with a Likert-type scale 
where 1= Strongly disagree to 5 = Strongly agree.  
 
The research team will meticulously track the number of potential participants screened, the 
number of enrolled subjects, completion of all study timepoints, and attrition from each arm.  
 
To examine the relationship of demographic variables, including gender, age, body mass index, 
body fat, ethnicity, and sun exposure to serum 25(OH)D levels in both groups, several other 
measurements will be obtained including the following:  
 
1. Body height (Ht) – Vertical height is measured at baseline using a Harpenden 
Stadiometer and recorded to the nearest 0.1 cm. The stadiometer is composed of a rigid 
vertical backboard with an attached rigid horizontal headboard which moves up and 
down the backboard. Final height was the average of two measurements taken by 
trained study staff. 
 

 
                                                                                                                                                       
 
 
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2. Body weight (Wt), Body fat (BF)/lean mass (Fat free mass), Basal metabolic rate – weight 
in pounds, percent fat mass and % lean mass, and metabolic rate at rest. The study team 
will utilize bioelectrical impedance analysis (BIA) to obtain body composition measures. 
The InBody 230 lean and fat mass assessment device has been shown to be comparable 
to the gold standard, Dual-energy X-ray Absorptiometry (DXA). It is maintained in the 
office suite where the project team is located; all team members are trained in its use.  
 
3. Demographic Questionnaire – Is administered at baseline and will be updated at 10 
weeks. This tool was created specifically for the study to document relevant personal 
and family history related to diet, medical conditions, stress fracture history, alcohol and 
tobacco use, and exposure to sunlight. It is critical to know the presence of any of the 
following habits or conditions: current medications, age, gender, ethnicity, and race. The 
tool also covered physical activity and environmental exposures. 
 
4. Vitamin D and Calcium Intake and Frequency Questionnaire22 – This questionnaire is 
administered in-person by study team at baseline. It is used to record average daily and 
weekly servings of foods high in vitamin D and/or calcium. The tool has been validated 
for use in young adults. Permission was obtained from the author for its use. The tool is 
designed as an Excel worksheet with built-in calculations that total the amounts of 
vitamin D and calcium in foods that are consumed on a daily or weekly basis. The 
reference for the nutrient values is the Academy of Medicine. The tool was modified 
slightly to capture vitamin D and calcium-containing foods and quantities consumed 
from Northwest sources, such as salmon and ultraviolet irradiated mushrooms. 
 
5. Serum biomarkers - Calcium and Parathyroid Hormone – standard blood tests 
performed at the same time as the 25(OH)D in order to provide a clinical interpretation 
in the setting of abnormal levels.  
 
6.5.2 Appropriateness of Measurements 
The Elecsys Vitamin D Total II assay is intended for the quantitative determination of total 25-
hydroxyvitamin D in human serum and plasma. The electrochemiluminescence binding assay is 
intended for use on Elecsys and cobas e immunoassay analyzers.  
 
Body composition measurements, biomarkers, and demographic questionnaires all represent 
valid and reliable methods to capture data relevant to a vitamin D investigation. All measures 
have been previously tested and used by this research team. 
 
6.5.3 Primary Efficacy Variable(s) 
Serum 25(OH)D level is the primary endpoint used to establish whether the treatment in the 
phototherapy kiosk group is equivalent to the oral vitamin D3 supplementation currently 
prescribed as the standard of care. It is expected that the serum 25(OH)D levels in both groups 
will rise over time and that the serum 25(OH)D levels will be equal to, or not less than, that of the 
oral supplementation group.   
 
A Device Usability Scale will be administered to the Kiosk Group to assess acceptability and 
feasibility. This 12-item Likert-type scale was adapted from the Digital Equipment Corporation 

 
                                                                                                                                                       
 
 
Page 12 of 15 
“System Usability Scale” (1986) and it will be administered to the Kiosk Group upon completion 
of the study.  
  
 
 
6.6 
Statistical Methods Planned in the Protocol and Determination of Sample Size 
6.6.1 Statistical and Analytical Plans 
The original analysis plan will be carried out using all available subject data points. No interim 
analysis will be performed.  Exploratory data analyses will be conducted on the serum vitamin D 
levels of participants assigned to either the oral vitamin D supplementation or kiosk group. The 
analysis will be restricted to participants with valid baseline serum vitamin D data and at least 
one follow-up blood draw. The Shapiro-Wilk test will be used to assess the normality of the data 
distribution. Measures of central tendency and dispersion are provided for continuous data as 
medians (mdn) with associated interquartile ranges (IQR). Summary statistics will be provided 
for categorical variables and include the number of participants as well as the prevalence within 
each group.  
 
6.6.2 Determination of Sample Size 
This is a pilot study therefore the appropriate sample size was estimated based on previous and 
current studies that achieved significance and involved this population and a similar approach to 
vitamin D supplementation.   
We requested approval to enroll twice the number required, or 120 subjects, in order to 
overcome the potential for a higher than expected attrition (30%), or a particularly high level of 
enthusiasm for the study from beneficiaries and civilians working in the hospital.   
Estimate Required Sample Size 
60 
Estimate Participant Drop Out / Withdrawal 
30% 
Total Enrollment Requirement 
Minimum of 78, requesting 120 
   
7.0   References 
 
1. He CS, Yong XHA, Walsh NP, and Gleeson M. Is there an optimal vitamin D status for immunity in 
athletes and military personnel? Exerc Immunol Rev 2016;22:42-64. 
 
2. Koutkia P, Lu Z, Chen TC, Holick MF. Treatment of vitamin D deficiency due to Crohn's disease with 
tanning bed ultraviolet B radiation.Gastroenterology. 2001 Dec;121(6):1485-
8. http://www.ncbi.nlm.nih.gov/pubmed/11729127 
 
3. International Commission on Illumination. Technical Report: Action spectrum for the production of 
previtamin D3 in human skin. ISBN 3 901 906 50 9. CIE 174:2006. 
 

 
                                                                                                                                                       
 
 
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4. Cranney C, Horsely T, O’Donnell S, et al. Effectiveness and safety of vitamin D. Evidence Report/Technology 
Assessment No. 158 prepared by the University of Ottawa Evidence-based Practice Center under Contract No. 
290-02.0021. AHRQ Publication No 07-E013. Rockville, MD: Agency for Healthcare Research and Quality, 2007. 
 
5. Grant WB, Boucher BJ. Requirements for Vitamin D across the life span. Biol Res Nurs 2011;13(2):120-33. 
 
6. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann 
Epidemiol 2009;19(7):468-83. 
 
7. Pérez-López FR. Vitamin D and its implications for musculoskeletal health in women: an update. Maturitas 
2007;58(2):117-37. 
 
8. Pérez-López FR, Brincat M, Erel CT, et al. EMAS position statement: Vitamin D and postmenopausal health. 
Maturitas 2012;71(1):83-8. 
 
9. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. 
Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. 
J Clin Endocrinol Metab 2011;96(7):1911-30. 
 
10. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clinical Nutr 2008;88:582S-586S. 
 
11.  LeBlanc E, Chou R, Zakher B, et al. Screening for Vitamin D Deficiency: Systematic Review for the 
U.S.Preventive Services Task Force Recommendation. Evidence Synthesis No. 119. AHRQ Publication No. 13-
05183-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2014. 
 
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