A Feasibility Study Addressing the Frequency of Low Level Laser Therapy for Reducing Central Adiposity and Weight in Overweight Individuals
Phase: NA
Conditions: Weight Loss
Sponsor: Mayo Clinic

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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A feasibility study addressing the frequency of 
Low Level Laser Therapy for reducing central 
adiposity and weight in overweight individuals. 
 
 
NCT02877004 
 
 
10/28/16 
 

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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Currently in the United States about 97 million adults are overweight, accounting for about 33% of the 
American adult population1.  Low level laser therapy (LLLT) is a new novel non-invasive procedure that 
removes excess fat without the negative side effects associated with surgical methods. LLLT also has the 
potential to enhance motivation for weight management as LLLT treatment can provide immediate feedback to 
the patient or study participant in the form of lost inches which can be seen by the individual. LLLT has been 
associated with reductions in waist circumference of 6-12 inches with 6 treatments.   
 
Clinically, the LLLT treatments can vary from 6 to 28 treatments and a frequency of 1-3 times per week 
depending on the patients’ preference and ability to pay.  Our research team conducted a previous feasibility 
study of 45 overweight/obese subjects looking at the use of 12 LLLT treatments over the course of 12 weeks 
(one treatment per week) with the end goal of reducing central adiposity.  In this prior study (IRB 14-002370), 
subjects were randomized to 1 of 3 conditions (LLLT, lorcaserin, and LLLT + lorcaserin).  This study 
demonstrated feasibility by recruiting the goal of 45 obese subjects within 3 months.  The subjects assigned to 
LLLT did not have any adverse events reported during the 6 months of the trial and although the sample size 
was too small for any significant findings, the LLLT did show a reduction in body circumference (2.3 to 4.0 cm 
reduction) and a reduction in weight (1 to 3.5 kg reduction).  At this point, the question still remains on the ideal 
frequency of LLLT treatments which are needed to see a significant loss in weight and reduction in body 
circumference.  Significant weight loss is defined as a reduction of 5% or more of the baseline weight. 
 
For the purposes of this study we will define overweight as having a body mass index [BMI] 25-29.9.  In this 
pilot study we will randomize 60 overweight individuals to one of three LLLT treatment schedules: 
 
1. 12 treatments of LLLT - 3 times per week  
2. 12 treatments of LLLT - 2 times per week  
3. 12 treatments of LLLT - 1 time per week  
 
The overarching purpose of this study is to obtain preliminary evidence regarding the most efficacious  
frequency of LLLT treatments to obtain at least a 5% weight loss and to produce reduction in body 
circumference.  
 
Hypothesis: We hypothesize that an increase frequency of LLLT treatments will produce a greater weight loss 
and greater reduction in body circumference when compared to a less frequent schedule of LLLT:   
 
Group 1 weight loss > Group 2 weight loss > Group 3 weight loss 
 
Group 1 reduction in body circumference > Group 2 reduction in body circumference > Group 3 
reduction in body circumference 
Aims, purpose, or objectives:  
 
1. To compare the % of weight loss and reduction in body circumference at the end of 4 weeks for 
overweight individuals undergoing  LLLT treatments at different frequencies  
 
 

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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Figure 2. LLLT device -  Zerona® by 
Erchonia 
 
Study Design and Methods 
 
Methods:   
 
Study Design - This will be an open label clinical trial with all study participants receiving LLLT. We will 
obtain preliminary data on the efficacy of LLLT based on varying frequency of the LLLT treatments.   We will 
focus this study on 60 overweight adults with a BMI of 25 to 29.9. We will assess changes in weight and waist 
circumference at end of treatment for group 1 (week 4) and group 2 (week 6) and group 3 (week 12).  
Participants will be randomized to receive LLLT treatments either 3 times a week for a duration of 4 weeks 
(group 1); 2 times a week for a duration of  6 weeks (group 2); or once a week for a duration of 12 weeks 
(group 3).  
 
Study Procedures: We will use standardized procedures to ensure that uniform instructions are provided to all 
participants and that recruitment and screening result in the enrollment of appropriate study participants. All 
Study Case Report Forms are paper documents and also function as study source documents. The data will be 
entered into an online electronic data program (Redcap) by research staff within 7 days of the completed study 
visit. Study participant data on this system will be identified using unique subject IDs, not personal identifiers. 
This data entry system will provide immediate feedback on the majority of data integrity issues, including 
implausible entries, and checks of consistency between variables. 
 
Study Processes and Procedures 
 
Intervention 
LLLT: Each LLLT device consists of a multiple-head low-level diode laser with 6 independent diode laser 
heads (Figure 2). Each diode emits 532 nm (green) laser light. In the active device (Erchonia1 LipoLaser, 
Erchonia Medical, Inc., McKinney, TX)2 each diode generates a 17 mW output. The average number of 
treatments can vary, depending on the adipose make up on the patient.3 In this trial, subjects will undergo 12 
treatments of LLLT at varying frequencies.  
The Erchonia® Zerona™ 2.0 Laser (which will be used in this study) has been approved by the FDA 
(K123237) as a non-invasive dermatological aesthetic treatment which can 
be 
used by individuals intending to reduce circumference of hips, waist, and 
thighs.  Justification for the assertion of anticipated safety and 
effectiveness of the Erchonia® Zerona 6 Headed Scanner (EZ6) for 
application to reducing body circumference is found through several FDA 
clearances for Erchonia® Low Level Laser devices for body circumference 
reduction indications. For all of the 510(k) clearances, the assigned Product 
Code is OLI, defined as follows:  
 Device: Fat reducing low level laser 
 Regulation Description: Low level laser system for aesthetic use 
 Definition: Non-invasive reduction in fat layer for body contouring 
 Technical Method: Use of low level laser energy to create pores in adipocyte cells to release  
lipids (triglycerides) 
 Target Area: Adipocyte cells within the subcutaneous fat layer of the body, this could include abdomen 
(waist), thighs and hips  

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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Under 21 CFR 878,5400, the FDA identifies this generic type of device as: “A Low Level Laser System for 
Aesthetic Use is a device using low level laser energy for the disruption of adipocyte cells within the fat layer 
for the release of fat and lipids from these cells for non-invasive aesthetic use.” 
 
The procedure administration protocol for each session is as follows: 
 The study participant is correctly fitted with the safety glasses. 
 The participant lies comfortably flat on his or her back on the procedure table such that the front area of 
the subject’s body is facing upwards. 
 The Erchonia® Zerona 6 Headed Scanner (EZ6) diodes are positioned at a distance of 6 inches above 
the subject’s lower and upper abdomen, stomach, centered along the body’s midline (the “line” that 
vertically “dissects” the body into two equal halves).  
 The Erchonia® Zerona 6 Headed Scanner (EZ6) is then activated for 30 minutes over the subject’s 
anterior (frontal) region. Each scanner emits to the subject a laser beam of approximately 17 mW with a 
wavelength of 532 nm, and creates a spiraling circle pattern that is totally random and independent from 
the others. These patterns overlap each other to guarantee total coverage within the target area of 
approximately 80 in²/516 cm². 
 The participant then turns over to lie flat on his or her stomach such that the posterior treatment area of 
the subject’s body encompassing the region spanning from the participant’s back down though the 
central body region is facing upwards. 
 The Erchonia® Zerona 6 Headed Scanner (EZ6) diodes are positioned at a distance of 6 inches above 
the posterior treatment area, centered along the body’s midline, the same as for the anterior region.   
 The Erchonia® Zerona 6 Headed Scanner (EZ6) is then activated for 30 minutes over the subject’s 
posterior region. Each scanner emits to the subject a laser beam of approximately 17 mW with a 
wavelength of 532 nm, and creates a spiraling circle pattern that is totally random and independent from 
the others. These patterns overlap each other to guarantee total coverage within the target area of 
approximately 80 in²/516 cm². 
 The participant’s safety glasses are removed and the procedure administration session is over. 
 
The Erchonia expert trained the DOM CRO staff in-person on the use and maintenance of the LLLT on 
December 12, 2013 for a prior study utilizing LLLT.  This training session has been documented.  They will 
be available for on the spot questions and for any online retraining, as needed.  The study coordinators will 
be under the direction of the nurse coordinator/supervisor (DFR). 
  
Subject Information 
 
Target accrual: We plan to enroll and screen a maximum of 75 overweight individuals with a BMI of 25-29.9 
kg/ m2 in order to accrue 60 research participants. 
 
Subject population:  Participants will be recruited from the local community through radio, internet postings, 
Mayo Clinic physician referrals.   
 
Based upon our recruitment data from recent weight loss studies and a wait list of participants  who are 
interested in this treatment, we estimate recruiting 3-4 study participants per week. Those who meet study 
criteria will be invited to participate in this open label study.  In this study, all 60 study participants will receive 

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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LLLT treatments.  Everyone will be in the study for 6 months, but will be in treatment for varying periods of 
time based  on the randomization group they will be assigned:  
1. 12 treatments of LLLT 3 times per week (M W F) for a duration of 4 weeks 
2. 12 treatments of LLLT 2 times per week (T Th) for a duration of 6 weeks 
3. 12 treatments of LLLT 1 time per week for a duration of 12 weeks  
 
Inclusion Criteria: Potentially eligible subjects must:  
1. be over 18 years of age;  
2. have a body weight of greater than 50 kg (110 pounds);  
3. have a BMI 25–29.9 kg/m2 ; 
4. be able to participate fully in all aspects of the study; and  
5. have understood and signed study informed consent. 
 
Exclusion Criteria: Subjects will be excluded if they:  
1. have used weight loss medications or participated in a weight loss program within the past 30 days;  
2. are currently taking supplements known to affect weight, such as garcinia cambrogia;  
3. have had weight fluctuations of 20 pounds or more in the past 6 months (self-report);  
4. have an implanted device (including pacemaker or lap band) in the targeted area of LLLT; 
5. have a known active eating disorder; 
6. have a known, active, untreated clinically significant psychiatric condition (alcohol or substance abuse, 
psychosis, bipolar disorder, or depression);  
7. have used an investigational drug within 30 days of study enrollment;  
8. are currently pregnant or lactating, or are of child-bearing potential or are likely to become pregnant 
during the medication phase and are unwilling to use a reliable form of contraception;   Acceptable 
forms include:  
a. Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants 
b. Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel 
that kills sperm) 
c. Intrauterine device (IUD) 
d. Total hysterectomy or tubal ligation 
e. Abstinence (no sex) 
9. have a history of any major cardiovascular events including heart valve disease, cardiac arrhythmias, 
congestive heart failure, acute coronary syndrome, stroke, transient ischemic attack, or peripheral 
vascular disease;  
10. have current uncontrolled hypertension (systolic > 160 mm Hg or diastolic > 95 mm Hg) documented on 
2 separate occasions;  
11. have clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, 
cardiovascular, lymphatic, respiratory, or metabolic disease (such as diabetes) or active cancer or are 
within 1 year of cancer remission;  
12. surgical intervention for body sculpting/weight loss, such as liposuction, abdominoplasty, stomach 
stapling, lap band surgery, etc. within 12 months prior to enrollment. 
13. medical, physical, or other contraindications for body sculpting/weight loss;  
14. any medical condition known to affect weight levels and/or to cause bloating or swelling;  
15. a diagnosis of, and/or taking medication for, irritable bowel syndrome; 
16. active infection, wound or other external trauma to the areas to be treated with the laser;  
17. known photosensitivity disorder;  

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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18. current active cancer or currently receiving treatment for cancer; or  
19. have a known history of any condition or factor judged by the investigator to preclude participation in 
the study or which might hinder adherence 
 
 Will a Certificate of Confidentiality be obtained? No. 
 
Research Activity 
  
1. 
  Drug & Device:  Drugs for which an investigational new drug application is not required. Device for 
which (i) an investigational device exemption application is not required; or the medical device is 
cleared/approved for marketing and being used in accordance with its cleared/approved labeling. (Specify in 
the Methods section) 
 
2. 
  Survey, Interview, Focus Group:  Research on individual or group characteristics or behavior, survey, 
interview, oral history, focus group, program evaluation, etc.  (Specify in the Methods section) 
 
Data Analysis 
 
Statistical Considerations 
The primary aim of this study is to assess the feasibility and potential efficacy of using LLLT at varying 
frequencies to reduce central adiposity in overweight individuals.  
 
The purpose of a phase II trial is to decide whether additional studies of the experimental regimen are warranted 
and to provide preliminary data for designing a larger phase III trial to confirm efficacy.  Although there has 
been debate about the value of formal statistical comparisons in phase II trials, we agree with those who 
propose that formal comparisons are appropriate under the caveat that phase II studies are not expected to 
provide reliable definitive comparisons using a traditional two-sided type I error rate of 0.05.(references).  For a 
randomized phase II trial, a one-sided test with a false-positive (type I error) rate of 0.20 is considered 
appropriate for the primary comparison to assess whether additional studies of the given regimen are warranted.  
 
 
For the current study the primary endpoint is change in waist circumference (WC) from baseline. For the 
primary analysis, the change in WC from baseline to week 4 will be compared across frequency groups.   
 
Data Analysis Plan:  
Data related to subject recruitment will be summarized, including the frequency of calls and the reasons for 
failing screening criteria.   
 
Baseline characteristics and treatment compliance of the enrolled participants will be presented overall and also 
separately for each of the treatment groups. In all cases, data will be summarized using mean ± SD for 
continuous variables and frequency percentages for nominal variables. Treatment adherence will be quantified 
for each individual by calculating the percentage of treatment sessions attended and the percentage of 
medication used. The percentage of subjects who discontinue study participation and the reasons for 
discontinuing study participation will be summarized.  Changes in measures of central adiposity and weight 
from baseline will be summarized at each study visit. The primary outcome of interest is change in waist 
circumference from baseline to week 4. For the primary comparison, the group receiving one LLLT session per 

LLLT Frequency Pilot 
PI: Ivana T. Croghan, PhD 
Mayo Clinic – NCT02877004 
 
 
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week will be the control group and the groups receiving two and three sessions per week will be considered the 
experimental groups. The mean change from baseline WC for each of the experimental groups will be 
compared to control using the two-sample t-test. For these comparisons, a one-tailed p-value of 0.20 or less will 
be considered evidence suggesting that studies utilizing increased frequency of LLLT sessions are warranted.  
 
Sample-size justification: 
The primary endpoint for the current investigation is change in WC from baseline to week 4. The group having 
one LLLT session per week will be considered the control group. From our previous study, the mean ± SD 
change in WC from baseline in those receiving 1 LLLT session per week was -1.1±1.9 cm.  In order to be 
considered meaningful, we would expect an increased frequency of LLLT sessions to result an additional 
reduction of approximately 1.0 cm. Under the assumption that the SD is 1.9cm, a sample-size of N=20 per 
group will provided statistical power (one-tailed, alpha=0.20) of approximately 80% to conclude that additional 
studies are warranted (i.e. detect a difference between groups of 1.0 cm). Therefore, a sample-size of N=20 per 
groups will be used for the present study. 
 
References 
 
1. 
Ogden CL, Carroll MD. Prevalence of Overweight, Obesity, and Extreme Obesity Among Adults: 
United States, Trends 1960–1962 Through 2007–2008. Health E-Stat [Web Page]. 2010; 
http://www.cdc.gov/NCHS/data/hestat/obesity_adult_07_08/obesity_adult_07_08.pdf. Accessed 01 Nov 
2011. 
2. 
Erchonia Corporation. Zerona. [Web Page]. 2011; http://www.myzerona.com/professional. Accessed 01 
Sept 2011. 
3. 
Mulholland RS, Paul MD, Chalfoun C. Noninvasive body contouring with radiofrequency, ultrasound, 
cryolipolysis, and low-level laser therapy. Clin Plast Surg. 2011;38(3):503-520, vii-iii.