Opioid Sparing Potential of Light-Induced Analgesia: a Pilot Trial of a Novel, Non-Pharmacological Treatment for Pain
Phase: NA
Conditions: Pain
Sponsor: Duke University

Opioid Sparing Potential of Light-Induced Analgesia: a Pilot Trial of a Novel, Non-
Pharmacological Treatment for Pain 
 
Protocol 1.14 Approved November 10, 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Purpose of the study  
This offers fascinating potential for use in opioid sparing multimodal analgesia while 
maintaining pain control, for which there is an urgent need. The green light effect is visually 
mediated. Further, the green-biased light spectrum involved can be obtained by filtering ambient 
light. Therefore, if such putative green light analgesia is possible in human populations, it would 
be inducible simply by using green lensed eyeglasses.   
Our long-term goal is to test the efficacy of eyeglasses-based green light therapy as an analgesic 
adjunct. In particular, we aim to assess green light therapy’s potential for broad adoption as an 
opioid sparing strategy while maintaining pain control. Reductions in opioid exposure are 
particularly important given links to opioid misuse risk. This aligns with national priorities 
aiming to identify interventions to prevent opioid misuse and abuse. The objective here, and the 
next step in pursuit of that goal, is to conduct a pilot trial testing clinical usage of green light 
therapy as an analgesic adjunct to opioid therapy. Our central hypothesis is that eyeglasses-based 
green light therapy will be well-tolerated and opioid sparing. The rationale for the proposed 
study is based on the published findings as described above. Namely, that green light 
visualization reduces pain responses. We expect that this effect will allow reduced opioid 
exposures in clinical care.  
We will conduct the proposed pilot trial in both acute and chronic pain conditions. 
Patients scheduled for thoracic surgery with anticipated post-operative opioid treatment (acute 
surgical pain) and patients with fibromyalgia currently treated with opioids (chronic pain) will be 
identified, enrolled, and randomized to one of three arms: 1. clear eyeglasses (control), 2. green 
eyeglasses or 3. blue glasses 
 
Design and Procedures 
Trial Procedures – Acute Pain group: 
Acute Pain group participants will be visited by study staff after their transfer to a floor unit 
(either normal care or step down; that is, after post-anesthesia care). Upon confirming their 
willingness participate, they will be randomized to receive either green, blue or clear glasses. 
Participants will be asked to wear their study glasses for at least 4 hours per day throughout their 
hospital stay and will be provided log books in which to record their glasses-wearing duration 
each day and any commentary they wish to share. During this visit, participants will also 
complete the PROMIS-57 Profile. The Patient-Reported Outcomes Measurement Information 
System (PROMIS) is a collection of patient-reported measures developed by an initiative of the 
National Institutes of Health as high-quality, well-validated, and standardized patient-
reported outcomes measures across multiple domains. The PROMIS-57 Profile is a detailed, 
standardized battery of PROMIS measures covering anxiety, depression, fatigue, pain intensity, 
pain interference, physical function, sleep disturbance, and ability to participate in social roles 
and activities. On day of discharge or at 48 hours postoperative, whichever comes first, study 

staff will again visit participants to collect the study glasses. Participants will again complete the 
PROMIS-57 Profile. During participants’ inpatient stays, study staff will continue to coordinate 
with the primary care teams to monitor for any issues arising from the study or the use of the 
study glasses. Providers will be supplied with contact information to provide any feedback they 
wish to share.  
For the postoperative patients in the study who are inpatient for the duration of the study, this is 
evaluated for them throughout their inpatient stay and the primary teams have the ability to 
address any sleep disturbance, mood change or change in the patients pain control per standard 
care. Should the providers caring for the patient or the patient themselves perceive the study 
intervention to be a significant contributor to the patients worsening condition, an adverse event 
will be recorded per the Data Safety Monitoring Plan and the patient will be withdrawn from the 
intervention/study. 
Trial Procedures – Chronic Pain group: 
Chronic Pain group participants will begin study procedures immediately following their 
enrollment. Participants will be randomized to receive either green, blue or clear glasses and will 
complete the PROMIS-57 Profile. Participants will be asked to wear their study glasses for 
at least 4 hours per day for a period of 2 weeks. Unlike the Acute Pain group in which pain 
will typically self-resolve with operative healing and the hospital stay provides a convenient and 
applicable treatment timeline, the appropriate duration of green light therapy for use in chronic 
pain states is unknown. Preclinical findings suggest the onset of analgesic effects after 3 days. 
However, such timelines rarely translate directly to human populations. Most pharmacological 
analgesics achieve effect onset within minutes to hours, although the analgesic effects of 
antidepressants upon chronic pain states (which may also involve modulation of descending pain 
control mechanisms) can require a week or longer to manifest. Here, we have chosen a moderate 
2-week duration to allow for a range of times-to-onset. Participants will be provided log books in 
which to record their glasses-wearing duration, average pain, and opioid use each day. They will 
also be invited to include any commentary they wish to share.  
For outpatients with fibromyalgia who are enrolled for 2 weeks all patients are administered the 
PROMIS-57 profile which evaluates the domains of sleep, mood and pain at enrollment, week 1 
and at week 2 when the intervention ends. If there is any worsening of the patients condition in 
any of the domains, they will be offered immediate evaluation and management for the same. 
Should the providers caring for the patient or the patient themselves perceive the study 
intervention to be a significant contributor to the patients worsening condition, an adverse event 
will be recorded per the Data Safety Monitoring Plan and the patient will be withdrawn from the 
intervention/study. 
All patients are provided with a phone number to call should they suffer from any side effects or 
worsening of their condition including any sleep disturbances. 
Participants in this group will be asked to complete the PROMIS-57 Profile at the 1-week and 2-
week time points. Two copies of the PROMIS-57 questionnaire will be given to the patient for 
completion at week 1 and week 2. A member of the study staff will call the patients at week 1 to 

ensure completion of the questionnaire over the phone with the subjects. The week 2 
questionnaire will be completed either over the phone (in the same way as week 1) or on site at 
the pain clinic. For patients completing the survey on site, the study staff will collect study 
materials (glasses and diary) at that visit. For patients completing the final study visit (week 2) 
over the phone, stamped and addressed shipping supplies will be provided to the patient for the 
return of the study materials (glasses and diary). Study staff will follow up with participants’ 
pain providers to obtain any relevant feedback. 
 
Selection of Subjects  
Subjects will be identified through chart review using MaestroCare reports. Inclusion/exclusion 
criteria for the study will be:  
Inclusion 
1. Scheduled for thoracic surgery for which post-operative opioid PCA is anticipated (Acute 
Pain group) OR currently treated with opioid therapy for fibromyalgia (Chronic Pain 
group)  
2. 18 years of age and older  
3. Able to wear study eyeglasses for at least 4 hours per day  
4. Agree to participate and provide written informed consent and HIPAA authorization  
Exclusion:  
1. Color blindness (patients will be administered a color blindness test online 
at https://colormax.org/color-blind-test/ 
 
 
Recruitment and Compensation  
In identifying and approaching all patients, the study team will coordinate with the primary 
clinical team. If the eligible patient agrees to hear more about the study, a study team member 
will attend, explain the study in detail, and obtain written informed consent. For patients who 
participate in remote enrollment, written electronic consent forms will be provided to the patient 
via email through REDCap and patients will sign and submit the e-consent. Study staff will then 
print a copy of the signed e-consent for our records and a copy will be automatically sent to the 
study participant as well. We will use the Duke hosted REDCap platform for collecting 
eConsent. 
 
 
Study Interventions 
Patients scheduled for thoracic surgery with anticipated post-operative opioid treatment (acute 
surgical pain) and patients with fibromyalgia currently treated with opioids (chronic pain) will be 
identified, enrolled, and randomized to one of three arms: 1. clear eyeglasses (control), 2. green 
eyeglasses or 3. blue eyeglasses.  

Patients are able to withdraw from the study at any time as is clearly stated in the consent: "You 
can choose to stop participating at any time without penalty or loss of any benefits to which you 
are entitled. However, if you decide to stop participating in the study, we encourage you to talk 
to your doctor first." 
For the postoperative patients (acute pain) who are inpatients for the time they are enrolled in the 
study, they continue to have access to opioid medications and other pain medications to address 
their pain per their primary teams per standard care.  
For the outpatients (chronic pain) with fibromyalgia who are enrolled in the study, should they 
suffer from worsening pain may withdraw from the study at any time as is clearly stated in the 
consent: "You can choose to stop participating at any time without penalty or loss of any benefits 
to which you are entitled. However, if you decide to stop participating in the study, we 
encourage you to talk to your doctor first." 
Participants are provided with a phone number to contact should they suffer from any side 
effects or worsening of their condition at which point the y would immediately be evaluated and 
managed to address their symptoms. 
The patients will be managed for their pain per standard of care with the regimen decided by 
their treating physician. The only intervention based on the study will be the introduction of the 
glasses which participants are required to wear for 4 hours during the day. There is NO change 
made to the patients pain management regimen, it is as per their primary treating physician. 
This is not standardized in the 3 groups as we will be recording the medications used for pain 
and their utilization.  
Patients will be exposed to ambient light, no standardized source of light. We will ask patients to 
document their 4 hours of usage of the glasses during each day for exact times worn and whether 
they were indoors or outdoors. In this pilot study we hope to understand patient usage patterns 
and compliance factors to inform a larger study in the future. 
The eyeglasses which will be used for this study are commercially obtained from online vendors. 
They are then tested to ensure they meet the below requirements 
Eyeglasses 
Thanks to recent fashion trends and the dramatic expansion of e-commerce enabling low-cost 
niche manufacturing, a wide array of eyeglasses in varying styles and colors are now easily 
available. To identify eyeglasses for use in this trial, we purchased several different examples 
from a major online retailer. We screened these eyeglasses for perceived lens color (as some 
eyeglasses relied on reflective coating to appear green, but did not transmit perceptibly green 
light), fit (across various study personnel and colleagues), subjective build quality, aesthetic 
acceptability, and availability of matching clear-lensed versions for use as controls. The 
remaining eyeglasses were subjected to transmission spectroscopy across the 425nm to 700nm 

visual spectrum. On the basis of these spectra, the eyeglasses with the most green-biased 
transmission will be chosen for use in this study. 
The brand we have tested with spectroscopy which meet the above requirements (shown on 
mannequin below) are WearMe Pro - Colorful One Piece Transparent Round Super Retro 
Sunglasses: Green. The blue glasses were selected from the same manufacturer: WearMe Pro - 
Colorful One Piece Transparent Round Super Retro Sunglasses: Blue. These specific glasses 
have been chosen as they are registered with the FDA as a medical device; registration of these 
glasses can be found on the FDA website (fda.gov) under registered medical devices. (Full 
spectroscopy analysis for the glasses has been attached).  
 
Data Analysis and Statistical Considerations  
We calculate that a total enrollment of 120 participants will be sufficient to provide greater than 
95% confidence in detecting issues with a 5% probability of occurrence. Divided evenly across 
Acute Pain and Chronic Pain groups (60 each) this sample will also provide approximately 80% 
confidence in detecting issues with a 5% probability of occurrence in only one group. This yields 
a 15 participant per condition (acute/chronic x green/clear/blue) sample size. Adding the blue 
glasses group to compare, continues to allow us a similar confidence in detecting issues with a 
5% probability of occurrence in one group.  
 
Interestingly, this chosen sample size also fulfills several other methods/guidelines for pilot trial 
sample sizes which range from 10 to 15 per condition. These methods have generally sought to 
power pilot trials to produce usable estimates of outcome measure values. While the 
appropriateness of such an approach is debated, it does suggest that our chosen sample size will 
be satisfactory to produce such estimates.