Morning Light Treatment at Home to Improve Glucose Metabolism in People at Increased Risk for Type 2 Diabetes
Phase: NA
Conditions: PreDiabetes, Circadian Dysregulation
Sponsor: Northwestern University

Clinical Trials Cover Page 
 
Official Title: Morning Light Treatment at Home to Improve Glucose Metabolism in People at 
Increased Risk for Type 2 Diabetes 
 
NCT Number: NCT03188263 
 
Date of the Document: May 3, 2018 

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PROTOCOL TITLE: 
Morning Light Treatment at Home to Improve Glucose Metabolism in People at Increased 
Risk for Type 2 Diabetes 
 
 
PRINCIPAL INVESTIGATOR: 
Kristen Knutson 
Department of Neurology 
312-503-1526 
kristen.knutson@northwestern.edu 
 
 
VERSION NUMBER: 10 
 
 
 
VERSION DATE: May 3, 2018 
 
  
OBJECTIVES: 
The primary purpose of this pilot study is to test a novel head worn light device (Re-Timer®) as 
an intervention to improve glucose metabolism in people with prediabetes. The hypothesis is 
that morning light treatment will improve glucose metabolism. This is a pilot study and the data 
from this project will be used to develop a larger clinical trial. 
 
 
BACKGROUND: 
Circadian Misalignment Impacts Risk for Type 2 Diabetes 
The central circadian clock, which regulates many circadian rhythms, is located in the 
suprachiasmatic nuclei (SCN, 1). In humans, central circadian timing is most reliably estimated 
from the onset of melatonin secretion in dim light (DLMO 2,3), which occurs ~2-3 h before 
habitual bedtime 4. Melatonin must be measured in dim light because it is suppressed by light 
5,6. In most humans (>70%), the endogenous period of the central circadian clock is greater than 
24 h 7,8, resulting in an endogenous tendency to drift later each day (phase delay). Such drift 
can result in a mismatch between behavioral cycles (sleep-wake and meal times) and internal 
biological time, known as “circadian misalignment”. There is evidence indicating that circadian 
misalignment is associated with increased diabetes risk and worse diabetic outcomes. Later 
sleep timing or self-reported eveningness (suggestive of circadian misalignment) is positively 
associated with obesity 9-12, and T2DM (OR 1.73-2.5, 13,14), and predictive of future increases in 
BMI 15, even after adjusting for potentially confounding variables such as age, sex, race, SES, 
physical activity and sleep duration. Later sleep timing is also associated with reduced glycemic 
control (higher HbA1c) in patients with T2DM 16, even after adjusting for age, sex, race, BMI, 
insulin use, depression, sleep debt and diabetes complications.  
 
Laboratory studies have also investigated the effects of circadian misalignment on diabetes 
risk in healthy humans. In one study, circadian misalignment resulted in an overall 6% increase 
in 28 h levels of glucose, despite a 22% increase in insulin, and 3 out of 8 subjects exhibited 2-h 
postprandial glucose responses >140- <210 mg/dl (prediabetic or diabetic levels) 17. In a second 
study, circadian misalignment resulted in an 8% increase in glucose but 12% decrease in insulin 
(fasting), and a 14% increase in glucose but 27% decrease in insulin (postprandial) 18. However, 
in these studies circadian misalignment also disrupted sleep, and disrupted sleep can impair 
glucose metabolism 19. A third study examined less severe circadian misalignment (2 x 2 
daytime sleep episodes interspersed with night-time sleep) and controlled for sleep by 

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comparing to a control condition with equivalent sleep loss 20. They found that circadian 
misalignment, independent of sleep loss, resulted in an additional 26% reduction in insulin 
sensitivity in men, with no compensatory increases in insulin release, reflecting a significant 
increased risk of T2DM. The authors concluded “this provides evidence in support of an intrinsic 
adverse effect of circadian misalignment on glucose metabolism.” (p1868, 20). 
 
The precise mechanism(s) by which changes in circadian timing could affect metabolism 
remain to be determined, but may include: (1) direct impact of SCN activity on glucose 
regulation via multisynaptic projections from the SCN to the liver and pancreas 21-23, (2) 
suppressed melatonin levels (light exposure during night), which is independently associated 
with increased insulin resistance in nondiabetics 24 and the development of T2DM 25. Indeed, 
the melatonin receptors on pancreatic beta-cells 26 preserve beta-cell function by preventing 
“functional overcharge” 27,28, (3) circadian misalignment results in peripheral molecular 
dysfunction 29, which downstream in the pancreas and liver can adversely impact diabetes risk 
30-32. Thus, “dysregulation of circadian secretion may be a key to the increase of T2DM” (p829, 
33). 
 
The Effect of Morning Light Treatment on Glucose Metabolism Remains to be 
Investigated 
Light is the strongest environmental signal that can alter circadian timing. Light is captured by 
the 5 retinal photoreceptors (rods, 3 cones, and the intrinsically photosensitive retinal ganglion 
cells [ipRGCs] 34,35). The ipRGCs are the primary circadian photoreceptor as they transmit the 
light signal directly to the SCN 34,36. The ipRGCs are most sensitive to short (~480 nm) 
wavelengths of light. Evening light shifts circadian timing later (phase delays) and can 
exacerbate the endogenous tendency towards circadian misalignment 37,38. By reducing 
exposure to evening light, there is potential to phase advance circadian timing 39,40. Conversely, 
morning light shifts the clock earlier (phase advance), and helps to realign circadian timing to 
more closely match the external environment, and reduce circadian misalignment 37,38. Thus, 
morning light is the most important light most humans receive every day.  
 
Given the associations between later sleep/circadian timing and risk for T2DM, one would 
expect morning light to be associated with a reduction in risk for T2DM. Four studies have 
examined these relationships. The first reported that the addition of daily morning light (1 h, 
5,000 lux) to a 6 week exercise program in 17 overweight/obese people led to a significant 
reduction in body fat that did not occur with exercise alone 41. A second study reported that daily 
morning light (45 mins, 1300 lux) for 3 weeks significantly reduced body fat and appetite in 34 
overweight women 42. The reduction in body fat was seen after 2 weeks of morning light 
treatment 42. A third study reported that a single dose of morning light (2 h, 60 lux) changed 
appetite regulating hormones (leptin, ghrelin) in a direction that would reduce hunger in 11 sleep 
deprived subjects 43. Last year, a study of healthy individuals reported that brighter light 
exposure (>500 lux) earlier in the day independently predicted a lower BMI, even after adjusting 
for age, sex, season, activity and sleep duration 44. All these studies point to the high potential 
for morning light treatment to reduce risk for T2DM, and highlight that many of the effects of 
morning light were observed in small sample sizes. Indeed, as others have recently stated: (1) 
“prescribed light exposure needs to be tested for its ability to restore the physiological dialogue 
between circadian mechanisms and metabolic pathways” (p7, 45) and (2) “interventional studies 
assessing the role of manipulating the master clock in the treatment of T2D are needed…the 
master clock can be manipulated by light therapy” (p326, 46). 
 
Preliminary Data 
Later Circadian Timing is Associated with Increased Risk for Type 2 Diabetes 
Drs. Knutson and Burgess collaborate on an ongoing R01 project to examine the cross-
sectional association between sleep/circadian timing and diabetes risk in persons without 

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diabetes. We examined the associations between the timing of sleep based on 1-week of 
actigraphy (average midpoint of sleep) and circadian timing  
(gold standard circadian phase marker in humans, DLMO), and fasting glucose levels in the first 
20 subjects with data (Figure 1). Results indicate that later sleep/circadian timing is significantly 
associated with 
higher fasting 
glucose even in 
those who do not 
currently have 
diabetes. These 
data are entirely 
consistent with the 
literature and 
represent the first 
data examining the 
relationship 
between the DLMO 
and fasting glucose.  
  
Creating a Placebo Light Treatment 
We now plan to test an active Re-timer® versus a placebo Re-timer®. We first considered 
creating a placebo Retimer® by retrofitting the Re-timer® with red LEDs (~660 nm), as this 
wavelength is further from the maximum sensitivity of the ipRGCs 34,36. However, this would 
have required additional ocular and electrical safety testing. Furthermore, subjects would have 
quickly discovered the red Re-timers® were not standard treatment, as we find many subjects 
look up their light devices on the internet. Thus, it appeared likely that subject expectations 
would have differed significantly between the standard versus red Re-timer®. Therefore, we 
enlisted the help of Dr. Dingcai Cao from Rush 
University (consultant on this grant), who used 
neutral density filters to markedly reduce the 
light intensity of the Re-timers® to a level that 
will not shift circadian timing. There are no 
safety concerns because the light from the 
already safety approved Re-timer® has simply 
been dimmed. Dr. Cao’s spectroradiometer 
recordings confirm that irradiance in these 
dimmed Re-timers® is reduced from 230 
μW/m2 to 3 μW/m2, and lux reduced from 500 
lux to 7 lux (Figure 2). Importantly, the placebo 
(dimmed) Re-timers® appear identical to those 
featured on the Re-timer® website and so are 
a highly believable placebo that should lead to 
similar expectations between treatment groups. 
 
Measures of Compliance to Light Treatment 
Dr. Burgess (Rush University PI) developed a measure of compliance to the Re-timer®, as none 
exists. By securing an Actiwatch Spectrum to the inside of the Re-timer® (does not unbalance 
frame), she can examine (1) green light to determine active Re-timer® on/off times and (2) 
activity to confirm both placebo and active Re-timers® are worn at the assigned times. 
INCLUSION AND EXCLUSION CRITERIA: 
Figure 2. Spectral power distribution of the 
active vs. placebo Re-Timer® measured with a 
PR670 spectroradiometer with a 2nm resolution. 
0.0E+00
1.0E-02
2.0E-02
3.0E-02
4.0E-02
5.0E-02
6.0E-02
7.0E-02
400
450
500
550
600
650
700
Relative spectral power
Wavelength (nm)
Active 
Re-Timer® 
Placebo 
Re-Timer® 
70
75
80
85
90
95
100
18:00
20:00
22:00
0:00
DLMO (clock time)
Fasting Glucose (mg/dl)
rho =  0.45, p=.045, n=20 
Figure 1.  Correlation between sleep/circadian timing and fasting glucose.
Later Circadian Timing
Later Circadian Timing
rho =  0.36, p=.16, n=17 
70
75
80
85
90
95
100
1:15
2:15
3:15
4:15
5:15
6:15
7:15
Midpoint of sleep (clock time)

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We will enroll 34 subjects (50% female, age 35-70 y) with prediabetes to complete the study.  
Laboratory sessions will occur during women’s follicular phase or women will be 
postmenopausal (≥6 months since last menses). These subjects will: (1) be overweight or 
obese (BMI≥25 kg/m2), (2) have prediabetes (HbA1c 5.7% to <6.5%),  and (3) be free of  severe 
obstructive sleep apnea (apnea-hypopnea index<30). The laboratory sessions will occur during 
women’s follicular phase or women will be postmenopausal (≥6 months since last menses). 
Women on oral contraceptives or hormone replacement therapy will be excluded (alters OGTT 
48,49 and melatonin 4). We will also exclude women who are pregnant, planning on becoming 
pregnant, or are breastfeeding. We will exclude men and women who have a child at home that 
does not sleep through the night. Adults unable to consent, individuals who are not yet adults 
(infants, children, teenagers), pregnant women, and prisoners are also excluded. 
 
Additional exclusion criteria include: history of type 1 or type 2 diabetes, use of diabetes 
medications, age outside 35-70 years (we will not enroll anyone older than 70 years because of 
a reduced response to light 50), smokers, shift workers, failing urine drug test (drugs of abuse, 
nicotine), eye disease, photosensitizing medications, regular hypnotic use (≥3 nights/week), , 
daily beta-blocker, NSAID or melatonin use (confounds DLMO), history of the following 
psychiatric disorders (confounds effect of light treatment, per relevant items from Mood 
Disorder, Psychotic Screening and Substance Use Disorders Modules of the Structured Clinical 
Interview for DSM-IV Axis I Disorders - Non-Patient Edition (SCID-IV/NP; 51): schizophrenia, 
bipolar depression, substance abuse, suicidal ideation, or obsessive compulsive disorder, 
PTSD). At screening subjects who score >20 on the Center for Epidemiologic Studies – 
Depression (CES-D) scale52 will also be excluded.  Additional exclusion criteria include irregular 
menses, history of cardiovascular disease (excluding hypertension), endocrine, kidney, 
gastrointestinal or liver disorder, seizures, and cancer. Subjects will be scheduled to participate 
≥ 1 month from travel outside the central time zone, and during a time with minimal special 
events. 
 
 
STUDY-WIDE NUMBER OF PARTICIPANTS: 
N/A Northwestern University is the only site where recruitment and participation in study will 
occur. 
 
 
STUDY-WIDE RECRUITMENT METHODS: 
N/A Northwestern University is the only site where recruitment and participation in study will 
occur. 
 
 
MULTI-SITE RESEARCH: 
N/A Northwestern University is the only site where recruitment and participation in study will 
occur. 
 
 
STUDY TIMELINES: 
The protocol will last 6-10 weeks depending on how soon after consent the subject can 
participate. We aim to complete recruitment by 05/31/2018 and primary data analysis by 
05/31/2019. 
 
STUDY ENDPOINTS: 

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The goal of this research project is to test a novel behavioral intervention, morning light 
treatment, to see if it can improve glucose metabolism in people with prediabetes.  
 
Primary Outcomes: 
Outcome 1: We will determine the effect of active versus placebo morning light treatment on 
glucose metabolism in individuals with prediabetes. 
 
Outcome 2: We will determine the extent to which circadian phase advances in the DLMO are 
related to improvements in glucose metabolism in individuals with prediabetes. 
 
 
PROCEDURES INVOLVED: 
Figure 3 presents an overview of the 5 week protocol. After screening for eligibility (see below) 
and informed consent, subjects will wear a wrist actigraph throughout the study. Subjects will 
complete a daily sleep and medication log, a questionnaire packet, and a 3-day food diary at the 
end of the baseline week and week 4. After the baseline week, there will be an overnight stay at 
the Northwestern University Clinical Research Center. Questionnaires and food diaries will be 
reviewed and body fat via bioimpedance will be measured. The DLMO will be assessed. 
Subjects will be given dinner 4 h before bedtime and consumed 3 hours prior to bedtime to 
ensure duration of fasting is at least 8 h and does not exceed 14 h. In the morning, a 3 hour oral 
glucose tolerance test (OGTT) will be performed in the Clinical Research Unit (CRU) 2 h after 
wake. Subjects will then begin a 4 week morning light treatment (see details below). The first 10 
subjects will be assigned active (bright), and the following 5 will be assigned placebo (dim) Re-
timer®. If more subjects are enrolled in the study, the next 10 will be placed on active (bright) 
treatment. Subjects will receive feedback on their compliance at weekly visits. Subjects will be 
paid $95 in cash at each visit to increase likelihood of participation and retention. In the final 
week, subjects will complete questionnaires and food diaries again. After the 4 week treatment, 
subjects will repeat the laboratory session for reassessment of the DLMO and OGTT. 
 
 
 
Subjects and Screening. As a first step in testing morning light treatment to improve glucose 
metabolism, we will enroll a sample of 34 subjects (50% female, ages 35-75 years), who are 
most likely to benefit from morning light. These subjects will: (1) be obese (BMI≥25 kg/m2), (2) 
have prediabetes (HbA1c 5.7% to <6.5%),  and (4) be free of severe obstructive sleep apnea 
(apnea-hypopnea index<30). Subjects will be screened initially over the phone or by completing 
the screening survey online via RedCap, and be asked to begin recording their bed times and 
wake times to determine the schedule for their light treatment. If potentially eligible, they will be 
invited to a pre-study screening visit, during which height and weight and HbA1c (finger stick of 
blood) will be assessed. Subjects will also need to pass a urine drug screen. Dr. Aleppo, a 
board-certified endocrinologist (co-investigator), will refer any subjects who are identified as 
having diabetes, for treatment. Any subjects identified as having prediabetes will also be 
Baseline 
At-home
7 Days
•3-day food diary
•Questionnaires
Baseline 
Lab Session
~20 hrs
• DLMO
• 3-h OGTT
Follow-up Lab 
Session
~20 hrs
•
DLMO
•
3-h OGTT
Wrist actigraphy throughout
Figure 3.  Protocol Overview
At-home Intervention
Four Weeks
• 1-h Morning Light treatment with
•
Active Retimer®, or 
•
Placebo Retimer®
• Weekly lab visit to check compliance
• 3-day food diary & questionnaires week 4

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referred to treatment, but also invited to participate in the final home screen for obstructive sleep 
apnea. Note that subjects who begin prediabetes treatment prior to the end of the study will be 
dropped, however, due to common delays in seeing a physician (over a month), this is unlikely 
to affect many subjects (as part of intent-to-treat analysis the last observation will be carried 
over). Subjects will be instructed in the use of the WatchPAT™ device (Itamar Medical Ltd.) to 
screen for obstructive sleep apnea. WatchPAT utilizes Peripheral Arterial Tone (PAT), a 
physiological signal that mirrors changes in the autonomic nervous system caused by 
respiratory disturbances during sleep. The automatic algorithm of WatchPAT analyzes the PAT 
signal amplitude along with heart rate and oxygen saturation to identify respiratory events and 
provide AHI. Dr. Park, who is board certified in sleep medicine and a consultant on this grant, 
will oversee the interpretation of the home sleep screen. Any subject with an apnea-hypopnea 
index≥15 will be informed of the result by study investigators and offered referral to a nearby 
sleep center for treatment and excluded from study participation.  
 
Laboratory sessions will occur during women’s follicular phase or women will be 
postmenopausal (≥6 months since last menses). Women on oral contraceptives or hormone 
replacement therapy will be excluded (alters OGTT 48,49 and melatonin 4). Additional exclusion 
criteria include: history of any form of diabetes, smokers, shift workers, eye disease, 
photosensitizing medications, regular hypnotic use (≥ 3 nights/week) daily beta-blocker, NSAID 
or melatonin use (confounds DLMO), history of psychiatric disorders (confounds light 
treatment), pregnancy/breastfeeding, irregular menses, history of cardiovascular disease 
(excluding hypertension), endocrine, kidney, GI or liver disorder, seizures, cancer. Recruitment 
will include advertising the study to current diabetes patients to recruit family members who may 
meet eligibility criteria. Dr. Aleppo sees over 350 diabetes patients each year. Recruitment will 
also include posting fliers, brochures, newspaper advertisements, and advertisements around 
Chicago, online, at various clinics in the Chicago area (as permitted by the local staff and 
healthcare providers) and attending community events. Note that recruitment at various clinics 
will involve only distributing flyers and brochures, but will not include sharing of patient 
information directly with us. Thus, the initial contact will be made by the volunteer. 
  
Light Treatment. The 1 h daily morning light treatment will start within a few minutes after each 
subject’s average wake time, as determined from the baseline week of actigraphy. The light 
treatment may start up to 1 h earlier to accommodate the subject’s usual morning schedule 
(work, child care) if required 53,54. Subjects are provided with an alarm set to the start of the 
morning treatment. A light log to note light on/off times and any interruptions to the light 
treatment will be provided. Subjects will be instructed to maintain their baseline sleep duration 
throughout the light treatment. Daily bed and wake time phone calls to a time-stamped voice 
mail will be reviewed daily with phone calls to subjects if required to ensure compliance. Wrist 
actigraphy data will be reviewed weekly in the presence of the subject. Importantly, the Re-
timer® light device is commercially available. The adjustable nose pad on each Re-timer® 
(whether active or placebo) will be individually fit to each subject to optimize the light treatment 
(Appendix). After the introduction to the Re-timer® (whether active or placebo), subjects will 
complete a treatment expectation item of 0 “expect no change” to 10 “expect to be healthier”. In 
between weekly visits, subjects will be encouraged to call research staff 24/7 with any questions 
about the light treatment. At the start of the second laboratory session, subjects will complete a 
treatment satisfaction item of 0 “not at all satisfied” to 10 “extremely satisfied”. 
 
 
Measures 
Oral Glucose Tolerance Test. During each laboratory session, a 3-h 75 gm OGTT will be 
performed in the CRC. After an overnight fast, a blood sample for fasting glucose and insulin will 
be obtained at -15 mins and 0 mins immediately followed by the oral administration of 75g of 

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dextrose. Plasma glucose and insulin blood samples will be collected at 30, 60, 90, 120, 150 
and 180 min after glucose ingestion. The primary outcome measure will be fasting glucose 
levels, a commonly used clinical marker. Fasting glucose levels are significantly correlated with 
HbA1c 55, which is a marker of glycemic control over 3 months that the ADA now recommends 
health care providers use to assess treatment effects 56. We will not measure HbA1c as an 
outcome measure in this pilot study because our 4 week intervention is unlikely to affect a 
measure of the 3-month average of plasma glucose levels. Secondary outcomes will be the 2-h 
glucose level and the Matsuda index (MI) of insulin sensitivity 57. These measures will allow us 
to ascertain whether there was an improvement in glucose metabolism. The CRC regularly 
performs these tests and Drs. Knutson and Aleppo are experienced in their interpretation. As 
noted above, subjects who are identified as having T2DM 56 at the screening visit will be 
notified, excluded from study participation, and referred to a physician/clinic. Subjects who are 
identified as having prediabetes 56 at the screening visit will be notified, included in study 
participation if they meet all other inclusion criteria, and referred to a physician/clinic. Dr. Aleppo 
will oversee these referrals. Subjects who begin diabetes treatment prior to the end of the study 
will be dropped, however, due to common delays in seeing a physician (over one month), this is 
unlikely to affect many subjects. If the original HbA1c screen suggested prediabetes but the 
fasting and/or 2-h glucose suggest diabetes, the subject will be retained in the study, but Dr. 
Aleppo will discuss the results with the subject. 
 
Dim Light Melatonin Onset. Subjects will be prompted by phone calls to refrain from NSAID 
use 72 h, and alcohol/caffeine 24 h, before each laboratory session and will be breathalyzed on 
arrival. Lights in the collection room are dimmed (<5 lux) beginning 6.5 h before and up to the 
subject’s habitual bedtime as determined from the baseline week of actigraphy. After 30 mins in 
dim light, saliva samples via salivettes will be collected every 30 mins according to standard 
procedures 58-61. Saliva samples are frozen until delivery to Rush where they are thawed, 
centrifuged, refrozen and shipped in dry ice to Solidphase, Inc. (ME) who performs direct RIA 
assay using standard commercially available ALPCO kits 8,62. Dr. Burgess will calculate the 
DLMOs and a trained research assistant will confirm accuracy before results are unblinded. We 
will calculate DLMO threshold as the mean of 3 low daytime points plus 2 times the SD of the 3 
points as per consensus report 63. The morning light treatment will phase advance the DLMO by 
~1-2 h 37,53,54. 
 
Wrist Actigraphy. Sleep timing and duration at baseline and during the intervention will be 
assessed continuously using wrist actigraphy (Actiwatch Spectrum, Philips, Inc.). Due to the 
unobtrusive nature of this device, habitual sleep behavior can be measured over weeks. Dr. 
Knutson has extensive experience working with actigraphy data 64-66. Actiwatch monitors feature 
digital integration, which is the most accurate measure of both movement level and intensity. 
Each subject will also complete a short sleep log every day, and call a time-stamped voice mail 
when they go to bed each night and when they wake up each morning 58,67. 
 
Food Diary. Subjects will complete a 3-day food diary for the last 3 days of the baseline week 
and week 4. The food diary will ask for the amount and types of food eaten and the time of 
meals and snacks. Diet analysis will be performed using ESHA Food Processor version 10.7, 
which calculates the overall calorie intake and estimated calories obtained from each nutritional 
component. Dr. Knutson has experience with this method and software and is using them in a 
current R01 project. 
 
Questionnaires. Sociodemographic information will be collected only once and will include age, 
sex, education, employment status and the MacArthur Socioeconomic Questionnaire 68. 
Subjects will complete several questionnaires at both baseline and week 4 of the intervention, 
including, an assessment of physical activity (International Physical Activity Questionnaire – 

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Short Version), and health factors (self-rated health 69, Physical Health Questionnaire 70) in case 
of significant changes in health during the study. We will also include several sleep and 
circadian questionnaires: circadian preference based on the Horne-Ostberg Morningness-
Eveningness (“owl-lark”) questionnaire 71, Munich Chronotype Questionnaire, Pittsburgh Sleep 
Quality Index, and Epworth Sleepiness Scale. We will also administer  Cohen’s Perceived 
Stress Scale 72, and the Center for Epidemiologic Studies - Depression Scale 52. Finally, we will 
include questionnaires to assess frequency of caffeinated beverage, alcohol and tobacco 
consumption. The Systematic Assessment for Treatment Emergent Effects questionnaire 
(SAFTEE) will be administered weekly to assess potential side effects of intervention.  
Questionnaire responses will be entered into the password-protected REDCap database and 
saved according to confidential study ID number.  
 
 
DATA AND SPECIMEN BANKING: 
N/A No data or specimen banking will occur. 
 
 
DATA AND SPECIMEN MANAGEMENT: 
Sample Size and Power Analysis 
We plan to enroll 34 subjects (50% female, age 35-70 y) with prediabetes. We conservatively 
estimate a 17% attrition rate (final n=28) which includes dropouts and noncompliance 
(noncompliance defined as <25% of morning light treatment, as per 77). This attrition rate is 
based on Dr. Burgess’ light treatment trials (5% such attrition), and the work of others (4 week 
bright light treatment group 6% attrition 77, 12 week bright light treatment group 19% attrition 78). 
Note that subjects who obtain only 25% of the prescribed active light (e.g. 15 min/day) are likely 
to obtain some benefit, as even only 15-20 mins of morning light can be clinically effective 79,80, 
and only a 12 min pulse can shift the DLMO 81. 
 
A primary goal of this project is to determine the effect sizes associated with morning light 
treatment to develop a larger RCT. However, for this pilot project we also estimated the required 
sample size to detect a clinically meaningful change in our primary outcome measure, fasting 
glucose level. We will also measure 2-h glucose and MI from the OGTT but have kept fasting 
glucose level as our primary outcome measure as it is a commonly used clinical measure. To 
estimate sample size for fasting glucose, we used a standard deviation (SD) of 9.0 mg/dl, which 
is the mean SD in a large sample of men and women with prediabetes 82. Using these values for 
a two-tailed independent t-test, with a total of 14 subjects per group, we will have 81% power 
(α=.05) to detect a change of 10 mg/dl, which is a clinically meaningful change and similar to 
that observed in a 2-week drug study 83. Thus we are well powered with an anticipated final 
sample size of n=28 to detect a clinically meaningful change in fasting glucose. 
 
Data Analysis 
Aim 1: For our primary analyses, we will examine the effect sizes in active treatment group. The 
analysis will use two-sided statistical tests and a nominal significance of 5%. Our primary 
analysis will focus on the pre-post measurements in the active group.  As a descriptive analysis, 
we will estimate the mean outcome measures at each time point for each subject and test time-
specific differences using non-parametric tests.  If we recruit sufficient subjects for the placebo 
condition, we will compare the effects in the two groups. 
 
Aim 2: To determine the extent to which circadian phase advances in the DLMO are related to 
improvements in glucose metabolism, we will first examine if the DLMO has changed 
significantly in the active light treatment group (and compared to placebo if possible), and then 

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examining if these differences are correlated with changes in glucose metabolism measures.  
 
Exploratory Aim: In a similar analysis to Aim 2, we will examine possible alternative mediators 
(body fat, activity, total caloric intake, and sleep fragmentation [wrist actigraphy]) through which 
morning light treatment may impact glucose metabolism (fasting glucose, 2-h glucose, MI). We 
will measure body fat because it was reduced in two previous light studies (reviewed in A.2.). 
We will measure physical activity because light treatment has an energizing effect 84. We will 
assess total caloric intake, as differences in circadian timing can impact diet 85. We do not 
expect changes in sleep duration as subjects will be instructed to maintain their habitual sleep 
duration during the treatment. However, a shift in circadian timing can impact sleep 
consolidation 86 so we will assess sleep fragmentation from wrist actigraphy. 
 
Confidentiality 
Study records will be kept confidential and data and records will be stored in locked cabinets in 
private offices.  Electronic data files will be stored on password-protected computers.  Data files 
and documents (with the exception of the consent form) will be stripped of identifying 
information and subjects will be identified only by a unique study ID code. All saliva samples will 
be deidentified using only the study ID code.  
 
Specimen Handling 
The saliva specimens will be stored in -20C freezers and then transported in insulated travel 
packs to Rush University by study coordinators. Once assayed they will be destroyed. They will 
be destroyed appropriately according to procedures regarding handling of biological specimens. 
 
 
PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF PARTICIPANTS: 
This study will recruit volunteers with prediabetes and study them for 5 weeks. Subjects will be 
assigned to one of two intervention groups: (1) active morning light treatment with a 
commercially available Re-timer® or (2) placebo morning light treatment with dimmed Re-
timer®. This project is considered to be “minimal risk” because the probability and magnitude of 
harm or discomfort anticipated in the research are not greater than those ordinarily encountered 
in daily life or during the performance of routine physical and psychological examinations or 
tests.  
 
All adverse events, serious and non-serious, occurring during the course of the study will be 
collected, fully documented, and reported to the Northwestern University Internal Review Board 
(IRB) by the Principal Investigator, Dr. Knutson. For each adverse event, the investigator will 
provide the onset, duration, intensity and treatment required, outcome and action taken. In 
addition to adverse event reporting, the investigators will report a summary of the protocol 
findings, subject recruitment, drop-outs, and events to the IRB annually. The physiological 
studies will be conducted in the Northwestern CRU, and as such, will be overseen by the CRU 
Data Safety Monitoring Board. All data will be kept confidential and in a locked cabinet. Only 
approved study personnel will have access to study related documents. 
 
 
WITHDRAWAL OF PARTICIPANTS: 
Participants are free to choose to stop participation in the study at any time.  They will be 
explicitly told that choosing not to be in this study or to stop being in this study will not result in 
any penalty to them or loss of benefit to which they are entitled.  Specifically, the choice to 
withdraw will not negatively affect the right to any present or future medical treatment to which 

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they are otherwise entitled.  If participants withdraw, the procedure will immediately stop, they 
will be asked to fill out paperwork regarding monetary compensation for the completed portion 
of the study.  Compensation will be prorated on the number of visits completed as described in 
the consent form.  We will ask for the reason for withdrawal, but participants are not obligated to 
provide one. Their data will be included in analyses as appropriate. 
 
Participants may be taken off the study without consent if: 
 
They are unable to meet the requirements of the study; 
 
If they begin treatment for prediabetes before completion of study; 
 
Their medical condition changes; 
 
If the study is stopped. 
 
 
RISKS TO PARTICIPANTS: 
One potential risk is that subjects may experience some distress when sharing personal 
information during the two telephone screening calls and while completing questionnaires for 
the study. To reduce distress about public disclosure, the meaning of confidentiality will be 
explained. Subjects will be explicitly instructed that revealing deeply personal information, by 
exploring the past or confiding to the investigators about personal secrets, is not considered part 
of the protocol and if revealed, will not be shared, recorded or disclosed to anyone. 
 
The clinical procedures involve some discomfort associated with the finger stick screen for 
HbA1c and later venipuncture associated with the OGTT assessment. There might be slight 
bruising at the site, which will recover in a short period of time. There is also slight risk of 
inflammation of the vein or infection. However, the research assistant who will conduct the 
finger stick and our nurses who perform the OGTT procedures will be highly trained and thus 
these risks are minimal. The amount of blood withdrawn is minimized to prevent significant 
blood loss. Furthermore, a study physician (Dr. Aleppo) will be available should any medical 
concerns arise. There is also the potential of discomfort from the equipment placement of the 
wireless WatchPAT™ device used for the home sleep apnea screen. Efforts will be made to 
minimize this discomfort, with the research assistant first demonstrating the correct application 
of the WatchPAT™ device on themselves, followed by the subject doing a test application in 
front of the research assistant, before the subject applies the device at home later that night (the 
screening visit will be scheduled to occur on a day in which the subject is available to do the 
home sleep apnea screen that night if they pass the screening visit).  
 
Subjects will receive a 1 hour morning light treatment for 4 weeks. Morning light treatment is 
already used in clinical practice, such as for winter depression 87-90 and circadian rhythm sleep 
disorders 91,92. Morning light treatment is considered safer than sunlight because there are no 
UV rays, and indeed no changes in extensive ophthalmologic examination were observed after 
up to 6 years of daily light treatment (in fall and winter) 93. Morning light treatment is associated 
with some side effects, the most common being headache, eyestrain, nausea and agitation 90, 
but often these side effects spontaneously remit 90,94, and patients rarely discontinue due to side 
effects 94. A rare but serious side effect is mania in bipolar patients who overexpose themselves 
to the light 90,94 but bipolar depressives are excluded from this study and all subjects will be 
provided with strict instructions to limit their light treatment to 1 hour/day. Additionally, the Re-
timer® device automatically turns off after 1 hour of use. Further, all subjects will be instructed 
to not permit family/friends to play with the Re-timers®, and to only turn the Re-timers® on 
during the scheduled time. Note that mania in response to morning light treatment is so rare that 
light treatment has even been clinically tested in bipolar patients and found to be safe 95. The 
active light treatment will result in light intensities greater than most indoor light, but much 
dimmer than sunlight on a bright day (about 100,000 lux). The active Re-timer® used in this 

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study is commercially available and already in use in the general population. The Re-timer® 
meets international ultraviolet and blue light hazard safety standards (standard ICNIRP 7/99 and 
CIE S009/E: 2002, also known as international standard IEC 62471/Ed. 1 published in 2006), 
and is safe (no UV light, no power in wavelengths <400nm). The placebo Re-timer® is also safe 
as the light has simply been dimmed. Finally, the circadian phase shifts (~1-2 hours) resulting 
from the active morning light treatment may lead to transient symptoms akin to jet lag after 
crossing 1-2 time zones, including transient sleepiness, fatigue and headache. These symptoms 
are similar to those experienced on a Monday morning after a late weekend. However, such ‘jet 
lag’ will be very short lived as the circadian phase shifts will likely complete within the first few 
days of morning light treatment. 
 
There is the risk of loss of confidentiality, but as described below, procedures are in place to 
minimize this risk. There are no other known risks involved in any of the other measurement 
procedures. Participation is voluntary and subjects may withdraw from the study at any time. 
 
 
POTENTIAL BENEFITS TO PARTICIPANTS: 
All subjects will receive the results of the finger stick HbA1c at screening and Dr. Aleppo will 
discuss the results with each subject as soon as possible. All subjects will receive the results 
from the home sleep apnea screen within 5 business days, and Dr. Park will discuss the results 
with each subject as soon as possible. Anyone who seeks treatment for OSA, even if AHI<15, 
will be excluded from the study (as part of intent-to-treat analysis the last observation will be 
carried over). If the original HbA1c screen suggested prediabetes but the fasting and/or 2-h 
glucose suggest diabetes, the subject will be retained in the study, but Dr. Aleppo will discuss 
the results with the subject. The information gained from this study will help to develop a larger 
randomized clinical trial to test a novel intervention, morning light treatment, to reduce risk of 
developing T2DM. The risks are only minimal and the risk-to-benefit ratio is very small. Subjects 
have the option of dropping out of the study at any time. 
 
Metabolic disorders such as diabetes and prediabetes are highly prevalent in the U.S. The 
primary goal of this study is to test whether morning light treatment may be an effective and 
feasible intervention to reduce risk for T2DM. If our hypotheses are correct, morning light 
treatment could be a feasible, effective, safe and non-pharmacological intervention to reduce 
diabetes risk in millions of Americans. 
 
 
VULNERABLE POPULATIONS:  
N/A. No vulnerable populations. 
 
 
COMMUNITY-BASED PARTICIPATORY RESEARCH: 
N/A. No community-based participatory research. 
 
 
 
SETTING: 
Research activities will take place in the Circadian Rhythms & Sleep Research Laboratory (NU 
Chicago campus) located at 710 N. Lake Shore Dr., Suite 500 and at Northwestern Memorial 
Hospital in the Clinical Research Unit. Study measurements will also be collected in the 
person’s home (actigraphy, light, WatchPAT). 
 
 

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RESOURCES AVAILABLE: 
Experienced research staff, knowledgeable of the protocol and trained in the devices and 
procedures outlined in the protocol, are already present and any new study personnel will be 
trained by senior researchers. All equipment required to conduct this research is already owned 
by the PI. A sleep laboratory is already in place.  
 
Participants will be recruited from the general public. Dr. Aleppo will recommend the study to 
her patients identified as prediabetic.   
 
 
PRIOR APPROVALS: 
University of Chicago IRB- see supporting documents.  
 
 
RECRUITMENT METHODS: 
Potential subjects will be recruited via digital and print advertising (e.g., flyers, poster, Doctor-to-
Patient Letter).Potential subjects may also be recruited online through Research Match and 
health registries (e.g., Women’s Health registry, NUCATS registry, and NMEDW) including but 
not limited to sites for professionals who see patients with early diabetes (prediabetes) or 
related conditions. Research Match is a secure online, national recruitment tool that is 
maintained by Vanderbilt University. ResearchMatch.org allows researchers to conduct 
feasibility or recruit potential study participants. Participants who are interested and released 
their contact information to the study team will be contacted via telephone or email. If 
participants cannot be reached via telephone the Research Match follow-up email will be sent to 
them via email. 
 
The Illinois Women's Health Registry was established and overseen by Northwestern 
University's Women's Health Research Institute at the Feinberg School of Medicine to 
encourage investigator-initiated research targeting women's health. The role of the Registry is to 
facilitate the recruitment and identification of women who may be eligible to participate in IRB 
approved research being conducted at Northwestern University and other research institutions 
across the state of Illinois. 
 
The General Research Registry, overseen by NUCATS, includes people who are interested in 
participating in research at Northwestern and have consented to be contacted about research 
studies for which they may be eligible. These potential participants will first be contacted via 
phone or email, provided detailed study information, and if interested in participating, 
encouraged to complete a pre-screening questionnaire to confirm if they meet study inclusion 
criteria. The Enterprise Data Warehouse (EDW) is also overseen by Northwestern Medicine. It 
consists of a comprehensive database of clinical and research data. Data requests from EDW 
can yield potentially eligible subjects, to whom the research team can reach out. 
 
Recruitment will also include advertising the study to current diabetes patients in order to recruit 
their potentially eligible family members. Dr. Aleppo, a co-investigator on this project, is an 
endocrinologist who has been treating diabetes patients for over 15 years and who sees over 
350 patients with diabetes each year at the Northwestern Hospitals. She will provide patients 
with a flyer with more information and tell them to have any interested family members to 
contact us. Recruitment will also include posting flyers, newspaper advertisements and 
advertisements around Chicago and online, and attending community events. Thus, the initial 
contact will be made by the volunteer. 
 

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For participating in this study the subjects will receive a total amount of $485 for completing the 
entire study. They will receive $10 in cash for completing the finger stick at screening. If they 
also complete the home sleep apnea screen, but do not continue the study, they will receive 
$40 in cash. Those that complete at least one week of the full study will receive a check at the 
end of the study totaling $95 for each week completed. Subjects who drop out prior to 
completing will be paid for the number of weeks completed.   
 
$95 for the first ambulatory week of actigraphy plus laboratory session 
 
$95 for week 1 of intervention (Week 2 of study) 
 
$95 for week 2 of intervention (Week 3 of study) 
 
$95 for week 3 of intervention (Week 4 of study) 
 
$95 for week 4 of intervention plus laboratory session (Week 5 of study) 
 
 
NUMBER OF LOCAL PARTICIPANTS: 
We will enroll 34 subjects (50% female, age 35-70 y) with prediabetes to complete the study. 
We conservatively estimate a 17% attrition rate (final n=28) which includes dropouts and 
noncompliance (noncompliance defined as <25% of morning light treatment, as per 77). 
 
 
CONFIDENTIALITY: 
To minimize loss of confidentiality, study records will be kept confidential and data and records 
will be stored in locked cabinets in private offices. Electronic data files will be stored on 
password-protected computers. Data files and documents (with the exception of the consent 
form) will be stripped of identifying information and subjects will be identified only by a study ID 
code. Only one file will have the name and contact information linked to the study code, and this 
information will be linked for the duration of the study. After this time, the linked information will 
be destroyed.  
 
 
PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF PARTICIPANTS: 
Study records will be kept confidential and data and records will be stored in locked cabinets in 
private offices.  Electronic data files will be stored on password-protected computers.  Data files 
and documents (with the exception of the consent form) will be stripped of identifying 
information and subjects will be identified only by a study ID code.  Only one file will have the 
name and contact information linked to the study code, and this information will be linked for the 
duration of the study (2 years).  After this time, the linked information will be destroyed. 
 
Note this protocol involves collaboration with Dr. Helen Burgess from Rush University.  Her 
expertise in assessing DLMO at home is required.  She will initially be part of the research team 
that meets with subjects to explain the at-home procedures and answer questions.  After the 
research team has had sufficient training from her, these meetings will occur without her 
presence.  Finally, she will assist with data analysis of melatonin to identify DLMO, but the data 
will all be de-identified before being shared.  This protocol will also be reviewed by the IRB at 
Rush University. 
 
 
COMPENSATION FOR RESEARCH-RELATED INJURY: 
N/A.  Research only includes minimal risk. 
 
 

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ECONOMIC BURDEN TO PARTICIPANTS: 
Participation is at no cost to subjects. 
 
 
CONSENT PROCESS: 
Interested subjects will call the study phone number on the flyer/ad, and the assigned research 
staff will discuss the study with the volunteer over the phone and ascertain potential eligibility. If 
the volunteer appears eligible and remains interested, the research staff will obtain verbal 
consent to request that the subjects record their bed times and wake times beginning that night 
and continuing until meeting for informed consent. This information is later used to prepare a 
schedule for their light treatment. The study coordinator will also set up a screening visit to 
explain the study in detail and obtain informed consent before the screening assessments are 
conducted. Thus, the initial contact will be made by the volunteer. Verbal consent will be given 
by the subject over the phone to begin recording bed time and wake times before coming into 
the screening visit and written informed consent will be obtained after all details of the study 
have been explained by one of the study personnel and the subject has received satisfactory 
answers to all of his/her questions. In the Consent Form, it will be emphasized that subjects 
may discontinue participating at any time and still receive prorated compensation for any 
procedures they have completed. The study coordinator will inform potential subjects that 
participation is completely voluntary, and they may withdraw at any time without penalty or 
running the risk of jeopardizing current and future treatment at Northwestern Hospitals or Rush 
University Medical Center. 
 
 
PROCESS TO DOCUMENT CONSENT IN WRITING: 
An IRB approved consent form will be signed by each participant. 
 
 
DRUGS OR DEVICES: 
Device 
Manufacturer 
IDE Class 
Actiwatch Spectrum Pro 
Philips Respironics 
Non-significant Risk 
ReTimer 
SMR Automotive Australia 
Non-significant Risk 
WatchPAT 
Itamar Medical Ltd 
Non-significant Risk 
 
Actiwatches, ReTimers, and the WatchPAT will be stored in dry, temperature-controlled, locked 
offices accessible only to Circadian Rhythms & Sleep Research Laboratory staff. Subjects are 
given an actiwatch, WatchPAT, and ReTimer for wear at home after adequate training and are 
required to return the devices upon finishing the screen or the full study. All devices will be 
cleaned, updated, and calibrated as per manufacture requirements.  
 
 
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Notebook. 2014; http://www.macses.ucsf.edu/research/socialenviron/. Accessed 
9/17/2014. 
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Idler EL, Angel RJ. Self-rated health and mortality in the NHANES-I Epidemiologic 
Follow-up Study. Am J Public Health. 1990;80(4):446-452. 
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Kroenke K, Spitzer RL, Williams JB. The PHQ-15: validity of a new measure for 
evaluating the severity of somatic symptoms. Psychosom Med. 2002;64(2):258-266. 
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Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-
eveningness in human circadian rhythms. Int J Chronobiol. 1976;4(2):97-110. 
72. 
Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health 
and Social Behv. 1983;24:385-396. 
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Hughes ME, Waite LJ, Hawkley LC, Cacioppo JT. A Short Scale for Measuring 
Loneliness in Large Surveys: Results From Two Population-Based Studies. Res Aging. 
2004;26(6):655-672. 
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McNeilly MD, Anderson NB, Armstead CA, et al. The perceived racism scale: a 
multidimensional assessment of the experience of white racism among African 
Americans. Ethn Dis. 1996;6(1-2):154-166. 
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Cohen S, Hoberman H. Positive events and social supports as buffers of life change 
stress. Journal of Applied Social Psychology. 1983;13:99-125. 
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Marteau TM, Bekker H. The development of a six-item short-form of the state scale of 
the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol. 1992;31 ( Pt 
3):301-306. 
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Michalak EE, Murray G, Wilkinson C, Dowrick C, Lam RW. A pilot study of adherence 
with light treatment for seasonal affective disorder. Psychiatry Res. 2007;149(1-3):315-
320. 
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Friedman L, Zeitzer JM, Kushida C, et al. Scheduled bright light for treatment of 
insomnia in older adults. J Am Geriatr Soc. 2009;57(3):441-452. 
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Virk G, Reeves G, Rosenthal NE, Sher L, Postolache TT. Short exposure to light 
treatment improves depression scores in patients with seasonal affective disorder: A 
brief report. International journal on disability and human development : IJDHD. 
2009;8(3):283-286. 
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Goel N, Etwaroo GR. Bright light, negative air ions and auditory stimuli produce rapid 
mood changes in a student population: a placebo-controlled study. Psychol Med. 
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Chang AM, Santhi N, St Hilaire M, et al. Human responses to bright light of different 
durations. J Physiol. 2012;590(Pt 13):3103-3112. 
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Ferrannini E, Manca ML. Identifying glucose thresholds for incident diabetes by 
physiological analysis: a mathematical solution. Am J Physiol Regul Integr Comp 
Physiol. 2015;308(7):R590-596. 
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Kim SH, Abbasi F, Lamendola C, et al. Benefits of liraglutide treatment in overweight 
and obese older individuals with prediabetes. Diabetes Care. 2013;36(10):3276-3282. 
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Kasper S, Rogers SL, Yancey A, Schulz PM, Skwerer RG, Rosenthal NE. Phototherapy 
in individuals with and without subsyndromal seasonal affective disorder. Arch Gen 
Psychiatry. 1989;46(9):837-844. 
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Kanerva N, Kronholm E, Partonen T, et al. Tendency toward eveningness is associated 
with unhealthy dietary habits. Chronobiol Int. 2012;29(7):920-927. 
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Dijk DJ, Czeisler CA. Paradoxical timing of the circadian rhythm of sleep propensity 
serves to consolidate sleep and wakefulness in humans. Neurosc Lett. 1994;166:63-68. 
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Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment 
of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 
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Lewy AJ, Bauer VK, Cutler NL, et al. Morning vs evening light treatment of patients with 
winter depression. Arch Gen Psychiatry. 1998;55(10):890-896. 
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Pail G, Huf W, Pjrek E, et al. Bright-light therapy in the treatment of mood disorders. 
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Morgenthaler TI, Lee-Chiong T, Alessi C, et al. Practice parameters for the clinical 
evaluation and treatment of circadian rhythm sleep disorders. An American Academy of 
Sleep Medicine report. Sleep. 2007;30(11):1445-1459. 
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Reid KJ, Burgess HJ. Circadian rhythm sleep disorders. Prim Care. 2005;32(2):449-473. 
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Gallin PF, Terman M, Reme CE, Rafferty B, Terman JS, Burde RM. Ophthalmologic 
examination of patients with seasonal affective disorder, before and after bright light 
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Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: 
efficacy, protocol, safety, and side effects. CNS spectrums. 2005;10(8):647-663; quiz 
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Dauphinais DR, Rosenthal JZ, Terman M, DiFebo HM, Tuggle C, Rosenthal NE. 
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Permission to Take Part in a Human Research Study
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Version Date: 04/09/2018
Title of Research Study: Light Treatment to improve Diabetes Risk: A Pilot Study 
Investigator:  Kristen L. Knutson, PhD
Phone: (312) 503-1526
Supported By: This research is supported by the NIH, Northwestern University, and Rush 
University.
Why am I being asked to take part in this research study?
We are asking you to take part in this research study because you are a healthy adult between 
the ages of 40-65.
What should I know about a research study?

Someone will explain this research study to you.

Whether or not you take part is up to you.

You can choose not to take part.

You can agree to take part and later change your mind.

Your decision will not be held against you.

You can ask all the questions you want before you decide.
Why is this research being done?
The purpose of this study is to determine if a morning light device can help to improve blood 
sugar levels in people with an early form of diabetes ("prediabetes").
How long will the research last and what will I need to do?
We think you will be in the study for about 6 weeks, including the screening period. 
You will participate in a brief screening session which will include: a urine drug test, drawing a 
small amount of blood from your finger, wearing a device for 1 night on your hand/wrist to 
measure your sleep at home, and a single page sleep log to track your bed and wake times.
You will be asked to wear a wristwatch device at home for one week to measure your typical 
sleep patterns. You will be asked to complete questionnaires and food and sleep diaries.
You will also spend 2 overnight visits 4 weeks apart in our clinic. We will collect saliva and blood 
samples. We will measure your body fat by attaching sensors to your foot and hand. You will 
also have an “oral glucose tolerance test,” which measures how your body uses sugar. An IV 
will be inserted into one arm and blood will be sampled every 30 minutes for 3 hours, totaling 
about 5 tablespoons of blood.
You will be given a light device to wear for 1 hour after waking up, everyday for 4 weeks. The 
device is worn on your head and delivers light to your eyes. It looks like large glasses, and can 
be worn over your eyeglasses if you wear them. It is easy to put on and to go about your daily 
morning activities while wearing it.  You will continue to wear the wristwatch device to measure 
sleep during this time and complete sleep and food diaries.
Key Information: 
The first few pages of this document include a summary of this study to help you 
decide whether or not to participate. Detailed information is provided after the 
summary.
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More detailed information about the study procedures can be found under the section What 
happens if I say “Yes, I want to be in this research”?
Is there any way being in this study could be bad for me?
The study may include the following risks. There is a potential risk of experiencing skin pain or 
irritation from the IV blood draw. It is possible that information that we collect be visible to 
persons who are not part of the research team, but we will treat the information that we collect 
using the professional standards of confidentiality.
More detailed information about the risks of this study can be found under “Is there any way 
being in this study could be bad for me? (Detailed Risks)”
Who can I talk to?
If you have questions, concerns, or complaints, or think the research has hurt you, talk to the 
research team at (312) 503-4965 or Dr. Kristen Knutson at (312) 503-1526
This research has been reviewed and approved by an Institutional Review Board (IRB). You 
may talk to them at (312) 503-9338 or irb@northwestern.edu if:

Your questions, concerns, or complaints are not being answered by the research team.

You cannot reach the research team.

You want to talk to someone besides the research team.

You have questions about your rights as a research participant.
You want to get information or provide input about this research.
How many people will be studied?
Up to 34 people may participate in this study at Northwestern University.
What happens if I say “Yes, I want to be in this research”?
After reviewing this consent form and discussing the details of the study with study personnel, 
there will be a brief screening session where we will take some blood and measure sleep (see 
"Screening" on the next page). After screening, the rest of the study will last 5 weeks and 
includes 6 separate, weekly visits to the laboratory (not counting this one). Two of these visits 
are overnight stays in our sleep laboratory. For the last 4 weeks of the study you will be asked 
to wear a light device on your head (ReTimer ®) for one hour each morning.
Detailed Information:
The rest of this document includes detailed information about this study (in addition to the 
information listed above).
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Pre-screening
You have already completed pre-screening over the telephone or in person, which included 
asking about previously diagnosed conditions, such as diabetes.  We also had you complete 
two questionnaires that screen for sleep apnea (the Berlin and the STOP-BANG).  People with 
sleep apnea are not eligible for this study.
You provided verbal consent over the phone to record your bed times and wake times before 
coming in for the screening visit.
Screening:
You will have the following tests and procedures today to see if you can be in the study:

You will be asked to provide a urine sample which will be tested for recreational 
drug use. Recreational drugs interfere with the laboratory tests used to process 
saliva and blood samples and are strictly prohibited for participation in this study.

We will stick your finger to draw a small amount of blood to see if you have an early form 
of diabetes and to see if you are healthy enough to give more blood in the study. If you 
do not have an early form of diabetes, called pre-diabetes, you will not be able to be in 
this study. 

You will be asked to wear a device overnight on your wrist and hand to measure your 
sleep at home for one night.  You will be given instructions about how to do this. 

You will be given a single page sleep log to continue tracking your bed times and wake 
times until you come in to pick up equipment at the start of week 1, the Start-up visit, 
after which you will be filling out sleep diaries to record this information. 
If the results of these tests match what is needed for this study you will be allowed to participate. 
You will then be scheduled for the full study. 
Start-up visit: 
We will review the sleep recording done at home and if you qualify we will provide you with the 
equipment and materials necessary for week 1.  At this visit, you will be given a wrist activity 
monitor (similar to a wristwatch called an “Actiwatch”), sleep diaries, and food diaries.  
Week 1: 
During this week, you will wear the wrist monitor all day and night and complete sleep diaries 
each morning.  The activity monitor is water resistant.  It can be worn while showering, but not 
to be kept underwater for long periods of time (over 30 minutes).  Please do not wear while 
swimming. 
In addition, you will complete several questionnaires and on the last 3 days of this week, you will 
complete a 3-day food diary that asks for both the amount and types of food eaten and the time 
of your meals and snacks.
Laboratory visit #1: 
At the end of the week, you will spend approximately 20-24 hours in our laboratory.  We will tell 
you the specific time to arrive, but it will be early afternoon. Dinner will be provided. Saliva (spit) 
samples will be collected every half hour in the late afternoon and evening until bedtime. You 
will continue to wear the wrist activity monitor. 
In the morning, body fat will be measured by attaching sensors to your foot and to your hand.  
Then, you will have an “oral glucose tolerance test” (OGTT), which measures how well your 
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Version Date: 04/09/2018
body uses sugar.  An IV will be inserted into one arm.  Two blood samples will be taken 15 
minute apart and then you will drink a sugar solution within 5 minutes.  After that you will remain 
seated and blood will be sampled every 30 minutes through the IV. The last sample will be 
taken 3 hours after you drank the sugar solution.   The total amount of blood drawn will be 
approximately 5 tablespoons. 
After the OGTT, you will get lunch and a member of the research team will meet with you to 
discuss the next part of the study.  At this point you will be randomly assigned to receive either a 
low light level or a high light level. We will tell you at the end of the study which level you 
received.  We will then give you instructions on how and when to use the light device each 
morning. The light device is worn on your head and delivers light to your eyes. It looks like very 
large eye glasses, and can be worn over your eye glasses if you wear any. You will only wear it 
for an hour after waking up, every day over four weeks. It is easy to put on and to conduct your 
daily morning activities as you are undergoing treatment. After we have gone over the light 
device and associated questionnaires, you are free to leave. You will receive phone call 
reminders around the scheduled light treatment time for the first three days of wearing the light 
device, and text message reminders for the remainder of the study duration. 
Week 2:
At this visit, we will give you the specific times and how we would like you to use the light 
device. You will continue to wear the wrist activity monitor and complete sleep diaries.   At the 
end of this week, you will visit our laboratory and get a new wrist activity monitor to wear the 
following week. We will also discuss how the use of the light device is going and how often you 
used it. We will again discuss the rest of the study and the times to use the light device.  
Week 3:
You will continue to follow the instructions we give you about the light device.  You will continue 
to wear the wrist activity monitor and complete sleep diaries.  At the end of this week, you will 
visit our laboratory and get a new wrist activity monitor to wear the following week.  We will also 
discuss how the use of the light device is going and how often you used it. We will again discuss 
the rest of the study and the times to use the light device.
Week 4:
You will continue to follow the instructions we give you about the light device. You will continue 
to wear the wrist activity monitor and complete sleep diaries.  At the end of this week, you will 
visit our laboratory and get a new wrist activity monitor to wear the following week.  We will also 
discuss how the use of the light device is going and how often you used it. We will again discuss 
the rest of the study and the times to use the light device.
Week 5:
You will continue to follow the instructions we give you about the light device.  You will 
continue to wear the wrist activity monitor throughout the study and complete sleep diaries.  In 
addition, you will complete the questionnaires and a 3-day food diary at the end of this week 
that asks for both the amount and types of food eaten and time of meals and snacks.  At the 
end of this week you will spend another day in the laboratory.
Laboratory visit #2: 
At the end of Week 5, you will spend approximately 20-24 hours in our laboratory.  We will 
tell you the specific time to arrive, but it will be early afternoon. Dinner will be provided. This 
session will be the same as the first laboratory session.  Saliva (spit) samples will be collected 
every half hour in the late afternoon and evening until bedtime. You will continue to wear the 
wrist activity monitor. In the morning, body fat will be measured by attaching sensors to your 
foot and to your hand.  Then, you will have another “oral glucose tolerance test” (OGTT), which 
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Version Date: 04/09/2018
will include 8 blood samples taken through an IV every 10-30 minutes over 3 hours. Total 
amount of blood withdrawn will be approximately 5 tablespoons. After the OGTT you will get 
lunch.  Afterwards, you are free to leave.  
The blood and saliva samples that we collect from you will be frozen and stored indefinitely for 
potential future research.  These samples will be stored using a unique code and not your 
name.  
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Version Date: 04/09/2018
Day by Day Outline of the Full Study
Week 1
Day 1
Start-up Visit
Pick up equipment, sleep diaries, food diary and instructions
Starting wearing wrist activity monitor
Days 2 – 4
Continue to wear wrist actigraphy
Complete sleep diary
Days 5 – 7
Continue to wear wrist actigraphy
Complete sleep diary 
Complete food diary
Day 7 Arrive at laboratory at specified time (afternoon). 
Bring in sleep and food diaries.
Overnight laboratory session begins
Dinner will be provided
Saliva sampling every 30 minutes until bedtime
Continue to wear wrist actigraphy 
Day 8
Body fat will be measured in morning
3-hour oral glucose tolerance test (involves IV insertion for taking blood)
Lunch will be provided
Discuss remainder of study and light treatment with research team.
Leave in the afternoon.
Week 2
Day 8
Begin to use light device at specified times that we gave you
Continue to wear wrist activity monitor
Days 9 - 14 Continue to use light device at specified times that we gave you
Complete sleep diary each day
Continue to wear wrist activity monitor
Day 14
Visit to our laboratory (approximately 1 hour)
Bring in sleep diaries and light device
Discuss use of light device 
Get new wrist activity monitor & diaries
Week 3
Days 15-20
Continue to use light device at specified times that we gave you
Continue to wear wrist activity monitor
Complete sleep diary each day
Day 21
Visit to our laboratory (approximately 1 hour)
Bring in sleep and food diaries and light device
Discuss use of light device 
Get new wrist activity monitor & diaries
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Version Date: 04/09/2018
Week 4
Day 22-28
Continue to use light device at specified times that we gave you
Continue to wear wrist activity monitor
Complete sleep diary each day
Day 28
Visit to our laboratory (approximately 1 hour)
Bring in sleep diaries and light device
Discuss use of light device 
Get new wrist activity monitor & diaries
Week 5
Days 29-31
Continue to use light device at specified times that we gave you
Continue to wear wrist activity monitor
Complete sleep diary each day
Days 32-34
Continue to use light device at specified times that we gave you
Continue to wear wrist activity monitor
Complete sleep diary each day
Complete food diary each day
Day 35
Arrive at laboratory in early afternoon. 
Bring in sleep and food diaries and light device.
Overnight laboratory session begins
Dinner will be provided
Saliva sampling every 30 minutes until bedtime
Continue to wear wrist actigraphy 
Day 36
Body fat will be measured in morning
3-hour Oral glucose tolerance test (involves IV insertion for taking blood)
Lunch will be provided
Leave in the afternoon.
During this study, Dr. Kristen Knutson and her research team will collect information about you 
for the purposes of this research.   This information includes the following: height, weight, 
measure of body fat, hormone response to a sugar load, and some hormone levels. We also 
collect sleep data, wrist activity monitoring data, and questionnaires about sleep, behavior, and 
appetite and alertness, food diaries, dates, e-mail address, names, telephone numbers, medical 
record number, and social security number (for payment purposes).
What are my responsibilities if I take part in this research?
If you take part in this research, you will be responsible for completing the procedures, 
assessments, and visits stated above. You are also responsible for communicating with the 
study coordinator or investigator when you are unable to or unwilling to continue to study.
What happens if I say “Yes”, but I change my mind later?
You can leave the research at any time it will not be held against you. If you decide to leave the 
research, contact the study coordinator or investigator so that they can cancel scheduled visits 
and assess the payment you qualify for according to the breakdown detailed later in this 
document. 
Choosing not to be in this study or to stop being in this study will not result in any penalty to you 
or loss of benefit to which you are entitled.  Specifically, your choice not to be in this study will 
not negatively affect your right to any present or future medical treatment, your class standing 
(for students enrolled in a class at NU), or your present or future employment (for employees at 
NU or its affiliates). If you withdraw from the study before you finish, we will still include your 
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Version Date: 04/09/2018
data in our analyses. We will ask you for the reason you are withdrawing, but you are not 
required to provide one.  Once you withdraw from the study, no more data will be collected.
Detailed Risks: Is there any way being in this study could be bad for me?
IV Insertion and Blood Draw Risks

Temporary pain

Bleeding

Slight bruising

Possible inflammation 

Possible fainting

Possible infection

Care will be taken to avoid these complications. An experienced research nurse will insert 
the IV under sterile conditions.
Confidentiality Risks

It is possible that information that we collect may be visible to persons who are not a part of 
the research team.  

We will treat the information that we collect using the professional standards of 
confidentiality. Please see specific information about this in the “Confidentiality” section on 
page 7 of this consent form. 
Other:

If your answers during the screening interview show that you have depression and may be 
at risk of hurting yourself or others we will take you to the Emergency Department (ED) and 
will disclose that information to the ED physicians and nurses.
There may be other risks that could arise which are not reasonably foreseeable. If new 
information becomes available which could influence your willingness to continue, this new 
information will be discussed with you.
This study involves the use of your identifiable, personal information and there is a chance that 
a loss of confidentiality could occur. The researchers have procedures in place to lessen the 
possibility of this happening.  See the section below titled: “What happens to the information 
collected for the research?”. 
Will it cost me anything to participate in this research study?
There will be no costs to you or your insurance company resulting from your participation in this 
research study. However, you or your insurance company will be responsible for costs related to 
your usual medical care.
Will being in this study help me in any way?
If you agree to take part in this study there may or may not be direct medical benefit to you. We 
hope the information learned from this study will help us further understand whether the use of a 
light device like the Re-Timer can help treat or prevent diabetes.  
What happens to the information collected for the research?
Study records that identify you will be kept confidential. Study records will be kept in a locked 
office and are only accessible by members of the research team. Data will be coded so that you 
are not identified and will not contain information that can identify you. The data collected in this 
study will be used for the purpose described in the form. Data from this study may be used in 
medical publications or presentations. Your name and other identifying information will be 
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removed before this data is used. If we wish to use identifying information in publications, we 
will ask for your approval at that time. 
Efforts will be made to limit the use and disclosure of your personal information, including 
research study and medical records, to people who have a need to review this information. We 
cannot promise complete secrecy. Organizations that may inspect and copy your information 
include the IRB and other representatives of this institution. The research team includes the 
individuals listed on this consent form and other personnel involved in this study at the 
Northwestern University and Rush University. As part of the study, Dr. Knutson and her 
research team may report the results of your study-related procedures and tests explained 
above to the National Institutes of Health (NIH).  These include the information from the wrist 
activity monitor, the sleep recording and the questionnaires, as well as your age, sex, ethnicity, 
height and weight.  The information being sent will not contain any information that identifies 
you.
All samples will be deidentified using only the study ID code. After the saliva specimens 
collected in lab are assayed they will be destroyed at Rush University. In this study, you will be 
asked about illegal activities or highly personal behavior. We have obtained a Certificate of 
Confidentiality from the federal government. However, we may still be required under certain 
circumstances to release your information. 
The sponsor, monitors, auditors, the IRB, the Northwestern University Office for Research 
Integrity, the US Office of Research Integrity (ORI), the US Office for the Protection of Human 
Research Protections (OHRP), the US Food and Drug Administration (FDA) may be granted 
direct access to your medical records to conduct and oversee the research. By signing this 
document you are authorizing this access. We may publish the results of this research. 
However, we will keep your name and other identifying information confidential.
Data Sharing 
De-identified data from this study may be shared with the research community at large to 
advance science and health. We will remove or code any personal information that could 
identify you before files are shared with other researchers to ensure that, by current scientific 
standards and known methods, no one will be able to identify you from the information we 
share. Despite these measures, we cannot guarantee anonymity of your personal data.
Can I be removed from the research without my OK?
Dr. Knutson may decide to take you off of the study without your consent if:

You do not follow the instructions about light treatment;

You are unable to meet the requirements of the study;

Your medical condition changes;

If the study is stopped.
What else do I need to know?
If you become ill or get injured as a result of this study (medications, devices or procedures), 
you should seek medical treatment through your doctor or treatment center of choice. You 
should promptly tell the study doctor about any illness or injury.  
The hospital [university, researchers] will not pay for medical care required because of a bad 
outcome resulting from your participation in this research study. This does not keep you from 
seeking to be paid back for care required because of a bad outcome.
Payment
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For participation in this study you will receive a check at the end of the study for each week 
completed, as detailed below.  Northwestern University requires that you complete a receipt 
after receiving any cash, which involves simply printing and signing your name.  You will receive 
$10 in cash for screening blood test, and only if you do not qualify for the rest of the study, $40 
in cash for the home sleep test.

$95 for Week 1, including laboratory session

$95 for week 2 

$95 for week 3 

$95 for week 4 

$95 for week 5, including laboratory session
HIPAA Authorization
We are committed to respect your privacy and to keep your personal information confidential.  
When choosing to take part in this study, you are giving us the permission to use your personal 
health information that includes health information in your medical records and information that 
can identify you. For example, personal health information may include your name, address, 
phone number or social security number. Your health information we may collect and use for 
this research includes:

All information in a medical record 

Results of physical examinations

Medical history including an mental health diagnosis 

Lab tests, or certain health information indicating or relating to a particular condition as 
well diaries and questionnaires

History of substance or alcohol abuse 

History of mental health disorders (e.g. depression, anxiety) including prescribed 
medications, doses, and length of use. 
During this study you may be coming to a Northwestern Memorial Healthcare Corporation entity 
(for example, Northwestern Memorial Hospital, Prentice Women’s Hospital) for research 
appointments or to get clinical services, such as lab tests, needed for the study.  When that 
happens, you will be scheduled for these services through the NMHC computer system.  When 
a clinical exam or lab is done by NMHC or one of its employees for the purpose of this research 
study, that information will be kept in both NMHC’s clinical records and in the study records.
The following clinical providers may give the researchers information about you:  all current and 
previous health care providers, including but not limited to the Rehabilitation Institute of Chicago 
(RIC), Northwestern Medical Group (NMG), Northwestern Memorial Hospital (NMH), 
Northwestern Lake Forest Hospital (NLFH).
Once we have the health information listed above, we may share some of this information with 
the following offices or entities outside of Northwestern University and its clinical partners (or 
affiliates):  the Northwestern University Institutional Review Board Office and Office for 
Research Integrity; the US Office of Research Integrity; the US Office for Human Research 
Protections; the US Food and Drug Administration.  
Any research information shared with outside entities will not contain your name, address, 
telephone or social security number or any other personal identifier unless disclosure of the 
identifier is necessary for review by such parties or is required by law or University policy 
[except that such information may be viewed by the Study sponsor and its partners or 
contractors at the Principal Investigator’s office].
IRB #: STU00204710 Approved by NU IRB for use on or after 5/3/2018 through 5/2/2019.

Permission to Take Part in a Human Research Study
Do not sign this consent if today’s date is later than the stated expiration date above.
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Version Date: 04/09/2018

Authorized members of the Northwestern University workforce, who may need to see 
your information, such as administrative staff members from the Office for Research, 
Office for Research Integrity and members of the Institutional Review Board.

Clinical affiliates, including but not limited the Rehabilitation Institute of Chicago (RIC), 
Northwestern Medical Group (NMG), Northwestern Memorial Hospital (NMH), 
Northwestern Lake Forest Hospital (NLFH), and the Ann & Robert H. Lurie Children’s 
Hospital of Chicago (Lurie Children’s).  Your participation in this clinical trial may be 
tracked in an electronic database and may be seen by investigators running other trials 
that you are enrolled in and by your healthcare providers.

Clinical affiliates, including but not limited to Northwestern Medical Group (NMG), 
Northwestern Memorial Hospital (NMH), and Northwestern Lake Forest Hospital (NLFH), 
for purposes including, but not limited to, the affiliate’s provision of care to you and/or the 
affiliate’s scheduling of appointments and/or billing activities.

Other University research centers and University contractors who are also working on 
the study,

Study monitors and auditors who make sure that the study is being done properly, 

Government agencies and public health authorities, such as the Food and Drug 
Administration (FDA) and the Department of Health and Human Services (DHHS).
Those persons who get your health information may not be required by Federal privacy laws 
(such as the Privacy Rule) to protect it. Some of those persons may be able to share your 
information with others without your separate permission.However, Illinois law does not allow 
the re-release of HIV/AIDS, genetic testing, mental health and developmental disabilities 
information by the recievers of the information except in precise situations allowed by law. 
Also, Federal Confidentiality Rules, 42 CFR Part 2, prohibit making any further disclosure of 
substance use disorder information unless further disclosure of this information is expressly 
permitted by written consent of the person to whom it pertains or as otherwise permitted by 42 
CFR Part 2. 
The results of this study may also be used for teaching, publications, or for presentation at 
scientific meetings.  
Unless you revoke your consent, it will expire at the end of the research study. 
Although you may revoke consent to participation in this research at any time and in any format, 
you must revoke authorization for use or disclosure of your health information in writing. To 
revoke your authorization, write to:
Kristen L. Knutson, PhD 
Center for Circadian and Sleep Medicine
Department of Neurology
Northwestern University Feinberg School of Medicine
710 N Lakeshore Drive, Room 523
Chicago, IL  60611
You do not have to authorize the use or disclosure of your health information; however, you will 
not be allowed to take part in this research study. If you do not authorize the use or disclosure of 
your health information, it will not affect your treatment by health care providers, or the payment 
or enrollment in any health plans, or affect your eligibility for benefits.
IRB #: STU00204710 Approved by NU IRB for use on or after 5/3/2018 through 5/2/2019.

Permission to Take Part in a Human Research Study
Do not sign this consent if today’s date is later than the stated expiration date above.
Page 12 of 12
Version Date: 04/09/2018
A copy of this signed consent document, information about this study, and the results of any test 
or procedure done may be included in your medical records and may be seen by your insurance 
company.
Optional Elements:
The following research activities are optional, meaning that you do not have to agree to them in 
order to participate in the research study. Please indicate your willingness to participate in these 
optional activities by placing your initials next to each activity.
I agree
I disagree
_______
_______
The researcher may contact me after I have finished participating 
in the study to clarify and ask questions about my responses to 
questionnaires and my performance on study activities.
_______
_______
The researcher may contact me in the future to see whether I am 
interested in participating in other research studies by the 
Principal Investigator of this study.
_______
_______
The researcher may retain any leftover blood or tissue samples 
taken during the study. These samples may be used for other 
research not related to this study. These samples will be retained 
in non-identifiable form, meaning that there will be no information 
associated with the blood or samples that will allow anyone to 
readily ascertain my identity. 
Your signature documents your permission to take part in this research.  You will be provided a 
copy of this signed document.
_______________________________________________      __________________
Signature of Participant                                                               Date
_______________________________________________
Printed Name of Participant
____________________________________________            __________________
Signature of Person Obtaining Consent                                     Date
______________________________________________________
Printed Name of Person Obtaining Consent
IRB #: STU00204710 Approved by NU IRB for use on or after 5/3/2018 through 5/2/2019.