A Twin Study of Obesity Pathogenesis Using fMRI
Phase: NA
Conditions: Obesity, Gliosis, Weight-Loss
Sponsor: University of Washington

A Cohort Study of Weight Loss and Gliosis 
NCT0357887 
4/19/2023 

 
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a. Background. Provide the rationale and the scientific or scholarly background for your proposed activity, based 
on existing literature (or clinical knowledge). Describe the gaps in current knowledge that your project is 
intended to address. 
 
Do not provide scholarly citations. Limit your answer to less than one page, or refer to an attached document with 
background information that is no more than three pages long. 
 
The long-term health benefits of obesity treatment are limited by the weight regain that almost universally 
follows a weight loss intervention, frustrating patients and clinicians alike. In lay terms, a new, higher “set 
point” seems to occur after people gain weight, and research shows that processes of energy homeostasis, 
directed by neurons in the arcuate nucleus of the hypothalamus, vigorously defend the higher level of adiposity 
for years, promoting weight regain after behavioral weight loss. Bariatric surgery, however, results in weight 
loss that is more durable over time. These phenomena remain incompletely understood. The current proposal 
endeavors to address this crucial scientific gap by investigating the brain’s role in the persistence of obesity 
and weight regain after weight loss. Specifically, studies in rodents show that diet-induced weight gain 
requires an inflammatory and cellular response, known as gliosis, within the arcuate nucleus of the 
hypothalamus and that this gliosis persists with continued dietary exposure. Importantly, gliosis is detectable 
in mice and humans by magnetic resonance imaging (MRI). Using MRI, the investigators discovered the first 
evidence of hypothalamic gliosis in obese humans. The investigators have also shown that hypothalamic 
gliosis is improved by Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy surgery, suggesting that the 
efficacy and durability of weight loss via bariatric surgery could be partially explained by its ability to reverse 
gliosis. New findings show that hypothalamic gliosis negatively impacts brain regulation of appetite. Based on 
such findings, the proposed research investigates novel questions about the possible implications of 
hypothalamic gliosis for clinical weight management. First, it will determine whether the extent of 
hypothalamic gliosis present when people with obesity start a behavioral weight loss program is related to 
their success in treatment or weight regain after treatment. Second, the current proposal also addresses the 
question of whether gliosis is reduced to a greater extent when weight loss occurs by RYGB or sleeve 
gastrectomy than by lifestyle change alone. Finally, this investigation uses a rodent study to test the role of 2 
different hypothalamic glial cell types in weight regain after weight loss. In sum, basic science advances have 
identified hypothalamic cellular responses that facilitate weight gain during times of nutritional abundance, but 
this biological process is also capable of forming glial scars that are detrimental to neuronal functioning. The 
current research therefore investigates the implications of hypothalamic gliosis for humans undergoing obesity 
treatment. Achieving a better understanding of the role of the brain in successful obesity treatment could open 
new avenues for research, intervention, and prevention to alleviate the health risks of obesity. 
 
b. Experience and preliminary work. Briefly describe experience or preliminary work or data (if any) that you or 
your team have that supports the feasibility and/or safety of this study.   
 
It is not necessary to summarize all discussion that has led to the development of the study protocol. The IRB is interested 
only in short summaries about experiences or preliminary work that suggest the study is feasible and that risks are 
reasonable relative to the benefits. Examples: You have already conducted a Phase 1 study of an experimental drug which 
supports the Phase 2 study you are now proposing to do; you have already done a small pilot study showing that the 
reading skills intervention you plan to use is feasible in an after-school program with classroom aides; you have 
experience with the type of surgery that is required to implant the study device; you have a study coordinator who is 
experienced in working with subjects who have significant cognitive impairment. 
 
 
 has already successfully and safely conducted several studies with similar design and procedures.  

 
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2. Obese, Lifestyle Cohort (Behavioral Weight Loss, BWL)  
3. Obese, Surgical Cohort or Surgical Weight Loss (SWL)  (RYGB or sleeve gastrectomy) 
2.2 Inclusion and exclusion criteria. Describe the specific criteria you will use to decide who will be included in your 
study from among interested or potential subjects. Define any technical terms in lay language. 
 
Inclusion Criteria: At the time of screening: 
HWC: BMI 18.5-24.9 kg/m2,  
BWL: BMI 30-<56 kg/m2,  
Bariatric: BMI 30-<56 kg/m2, eligible for RYGB or sleeve gastrectomy and not undergoing revision or 
reoperation. 
 
Exclusion Criteria:  
• 
Poorly controlled hypertension or coronary artery disease, or chronic disease (e.g. cancer, multiple 
sclerosis, autoimmune disease, rheumatic disease) 
     Blood Pressure > 160/100 mmHG  
     Heart Rate > 110 bpm 
• 
Chronic kidney disease (GFR <60 mL/min/1.73 m2), 
• 
Presence of cirrhosis (NALFD/NASH are acceptable), 
• 
Previous or planned (during the study period) obesity treatment with surgery (planned surgery ok for the 
SWL group) or a weight loss device. However, the following are allowed: (1) liposuction and/or 
abdominoplasty, if performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 
year before screening, (3) intragastric balloon, if the balloon has been removed > 1 year before screening 
or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before screening,    
• 
A1c > 8.5% in Bariatric group; A1c ≥  6.5% for BWL and HWC groups,  
• 
Current use of insulin (insulin ok for Surgical Weight Loss group, also called SWL), DPP-4 inhibitors, 
thiazolidinediones or medications known to alter metabolic function (e.g. atypical antipsychotics, 
corticosteroids), 
• 
Pregnancy or breastfeeding,  
• 
MRI contraindications (e.g. implanted metal, claustrophobia), or unable to have MRI or fit in MRI scanner 
• 
Current smoking/daily use of nicotine containing products (cigarettes, e-cigarettes, vaping or other 
nicotine containing products) or heavy alcohol use,  
• 
Weight >450 pounds (iDXA limit), 
• 
Weight-reduced from lifetime maximum weight by >16% (BWL and HWC only),  
• 
Weight not stable over past 3 months (±10% BWL and HWC, ±15% SWL) 
• 
T2D (for BWL or HWC), 
• 
Inability to participate in a weight loss program (BWL) 
• 
History of eating disorder or current eating disorder, currently enrolled in a weight loss program (ok for 
the SWL group provided weight stability and lifetime weight-reduced maximum conditions are met) or 
taking medications to lose weight 
• 
Severe food allergies 
• 
Any condition that the study physician determines to be unsafe for participation 
 

 
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, co-investigators on this project. For recruitment pre-screening purposes, medical record review is 
limited to inclusion and exclusion criteria. 
 
If eligible, an in-person screening visit will be scheduled with the research staff. At the start of the in-person 
screening consent will be obtained (if not obtained at clinic). At the screening visit a detailed medical history will 
be given, measurements such as weight, height and vitals will be collected, and blood draw will take place. If the 
phlebotomist is unable to draw blood after a few attempts, the participant will be asked if they can return on a 
different day to have their screening blood draw. The participant will not be offered additional compensation for 
this blood draw. MRI safety screening will be reviewed or completed and some questionnaires may be completed. 
For Behavioral Weight Loss participants, at screening a study physician (Dr. 
 or study 
physician) or a study nurse (ARNP) will conduct physical exam to evaluate cardiovascular, respiratory, 
neurological and endocrine function. Any abnormality will be shared with the subject who will be advised to 
follow-up with their primary care physician. Any findings that make it unsafe to proceed with Behavioral Weight 
Loss would end the subject’s participation in the study. 
 
We expect recruitment for the surgical cohort to require flexibility on our part. This section outlines how 
recruitment and screening could work for the surgical cohort. We will make subjects aware of the study as 
described in the first paragraph of this section. Other methods of making surgical candidates aware of the study 
will be described in this section. Flyers could be given to patients by clinic staff, and referred to research staff for 
more information. Flyers may also be distributed to patients with their surgery binder, and distributed by clinic 
staff at clinic visits. Research staff may directly approach patients in patient rooms or waiting area, or at group 
surgery-related education sessions run by the clinic. Research staff will use the clinic schedule in EPIC to identify 
days when surgical candidates will be at clinic, or to identify surgical candidates to approach about the study. 
Letters may be sent to patients who are planning to have bariatric surgery. Research staff would receive contact 
information from the clinic and send a letter describing the study (description in Zipline). Clinic staff may also 
provide medical record number, name and contact information via email or in person to notify research staff of 
potentially eligible subjects to approach about the study. Subjects who are interested in the study could 1.) call the 
research staff to go through phone screening and schedule the rest of the in-person components at a later time 
before surgery; 2.) go through the phone screening process in person with research staff in a private place in the 
clinic, be consented and go through the rest of in-person screening procedures at a later date. The visit would be 
scheduled with research staff to occur either at the clinic or UW SLU research location. Study staff would extract 
data for the screening questions from the patient’s medical record (height, weight, blood values, etc); 3.) the 
patient could complete the preliminary screening (same as phone-screening), and the consent process followed by 
in-person screening procedures all at once at the clinic location (some screening data would be extracted from the 
patient’s medical record). For in-person screening visits, surgical readiness and scheduling, we may receive 
medical record number (or name and contact information) from clinic staff via email, or in person.  
 
COVID accommodations for surgical cohort recruitment and screening: 
 
Email recruitment: Under the Waiver of Consent and Waiver of HIPAA, potentially eligible patients will be 
identified through clinic schedules. Study personnel will screen medical records in order to identify subjects likely 
to meet all inclusion and exclusion criteria.  A recruitment packet will be sent via email only to these individuals.  
The recruitment packet will include a study introductory message, a study summary, an MRI safety screening 
form, and a copy of the informed consent form (for informational purposes). The study introductory letter provides 
a brief description of the study, as well as a study email and telephone number to contact if the patient either would 
like to “opt out” of any future contact by study staff or if he or she has any questions about the study.  
 
For surgical cohort recruitment, we are adding a clinic outside of UW (
). If 
the clinic staff or surgeons identify an eligible person, they will briefly describe the study to the patient. If the 
person is interested in learning more, the clinic will send the contact info for interested patients to our study staff. 
We may send them a modified version of the email that we send UW surgery patients that generally describes the 
study, or set up a time to speak generally about the study over the phone.  

 
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If the patient is interested in study participation, a remote screening visit will be conducted prior to the baseline 
visit. This visit will enable study personnel to review the consent form in detail with the participant and complete 
the MRI safety form.  This visit will be held via telephone to minimize close contact between study participants 
and study personnel, which will reduce risk of COVID-19 transmission and conserve PPE. The participant will 
sign the consent form as other participants do with IRB approved methods described in this IRB Protocol, 
including in person at the beginning of the baseline visit.   
 
 
 UW Weight Loss Management Clinic is assembling a list of options for weight loss to provide to 
patients referred to their clinic in the coming months. The clinic is understaffed and will be unable to see new 
patients at the clinic until they resolve the staffing issue. They plan to give the appointment schedulers a list of 
options to give someone who wants to pursue weight loss right away and not wait indefinitely to begin treatment. 
One of the suggestions they want to include is the WEB study (study contact information and the web address for 
the listing on the ITHS research participant database). Staff talking points/script for UW WLMC staff to give this 
information will be uploaded to Zipline.  After the modification to add this recruitment method was approved, the 
clinic indicated that most communications from referrals occur via eCare.  The clinic described that a referral is 
received from a physician and the clinic staff can respond in eCare in a message sent through the patient’s 
electronic health record. Other ways this communication happens include phone, mail or email. This modification 
expands the way the clinic may be contacted and respond to potential patients. The same information will be 
shared (contact information, link to study description online (ITHS), and/or flyer from IRB approved flyer/talk 
points. 
 
The WEB study may use COVERED Registry to notify registry members who have given permission to be 
contacted about studies. COVERED Registry has IRB approval to notify potentially eligible registry members 
about IRB approved research studies. The COVERED Registry staff would contact registry members via letter or 
email to notify them about the study. In the case of WEBS, we will provide the link to the ITHS posting, contact 
information and a brief description about the study for COVERED Registry to use. 
 
We plan to post ads on Facebook to recruit participants. Surgical cohort and Healthy Weight cohort recruitment 
have slowed during the pandemic and we hope that Facebook ads will increase the pool of potential participants 
in any group (HWC, BWL and SWL). The ads we post on Facebook will use IRB approved ‘Flyer Text’ document 
content. Viewers who click on or select the ad will be brought to a webpage (Squarespace) that will provide a 
basic description of the study and a link to the REDCap preliminary screening questions. The website content is 
based on the IRB approved ‘Flyer Text’ document. Screenshots of the webpage will be uploaded to provide 
information to IRB but we prefer to retain flexibility to make minor changes to the website, and not have the 
website itself approved. From the website, interested people can opt to continue to preliminary screening 
questions (REDCap). We will ask permission in the REDCap form to ask questions and to collect their contact 
information. A PDF of the REDCap questions will be uploaded with this modification. When our research team 
reviews the screening information, our team will reach out to people who meet preliminary criteria to speak with 
them over the phone about the study, answer questions and go through phone screening as all participants 
experience. As with all participants, their participation is voluntary and they can decline to participate or 
continue at any point. 
 

 
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subjects will not undergo weight loss. SWL participants will have their body measurements confirmed at the 
Baseline visit and will not have a separate in-person study visit. 
 
The Human Subject activities listed in the NIH K24 award are not yet described in this application, but will be 
added at a later date. As of 10/7/2020, we are adding a brief sequence to all MRIs for all subjects. This sequence 
will last about 3 minutes and not require repositioning of the participant or use of contrast medium. Addition of 
this sequence does not change risks or the MRI study procedure for the participant in any noticeable way. We will 
tell participants when they screen for the study during the recruitment process that we will scan their brain and 
carotid area. We will tell already enrolled participants at the time of scheduling or prior to their next MRI/study 
visit that this sequence will be added to remaining MRIs at their study visits. 
 
COVID Accommodations: We will contact participants by phone or email a few days before in-person visits or 
procedures to screen them for COVID symptoms and will have them complete a COVID-19 screening attestation 
upon arrival for their in-person visit/procedures. We will read the attestation questions over the phone or email the 
form. We have uploaded an attestation document. All employees, including research staff, complete attestation to 
being COVID symptom free each workday. 
 
Depending on COVID related state or facility requirements, we will alter study visits as needed, make some 
procedures remote or not include procedures that cannot be conducted safely. For example, for the time being we 
will not include indirect calorimetry, but we may again in the future. We will ask participants to wear masks for 
the whole visit. Some facilities, such as the research MRI facilities, will ask for and keep contact information for 
the participant to be used for contact screening for approximately one month. We will make facility required 
changes for COVID precautions. The Clinical Research Unit, research MRI facility (BMIC and DISC lab) and 
Fred Hutch Nutrition Kitchen are the groups and facilities we conduct research procedures with for WEB study. 
 
Surgical cohort subjects will be pre-screened via review of medical records.  Prior to the surgery date, a 
screening visit will be held via phone call or Zoom to obtain informed consent and HIPAA authorization. 
Participants will sign consent as described below or just before beginning research procedures at baseline visit. 
 
Consent: We are adding the option of remote informed consent process and additional ways to obtain signature. 
This description was created in consultation with 
. We will provide a blank consent form to the 
participant (we will send by mail, email, share the screen during Zoom, or put it in REDCap to share for the 
discussion and consenting process). Research staff will have a discussion with the participant by phone or Zoom to 
review the consent form and answer questions.  
 
We will offer a few options to collect and document signature from the subject with research staff as witness. We 
will provide a blank consent form signature page that the subject will print out, or we mail a signature page to the 
subject. We will ask the subject to photograph the signature page and email or text a photo of it to us and will will 
print out; or the subject could mail the signature page to us. We will or could provide SASE for return of 
signed consent. We may also ask the subject to send a photo of the signed consent page to us by email/text before 
they mail it to us. Participants could also sign in person at the in-person screening visit prior to starting research 
procedures, or signature could be collected digitally via Docusign or REDCap.   
 
We may create short instructional videos to include during consenting process (or if a participant needs additional 
review of instructions at a later time), but not in place of a conversation over the phone and/or Zoom, etc. The 
videos would provide visual demonstration of how to use Actigraphs, or possibly to accurately do 
anthropomorphic measurements such as waist, hip and neck circumference, and height measurement at home. We 
could also send videos as reminders for procedures when we ask participants to complete research 
procedures remotely. 
 
 

 
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In-Person Screening: Due to COVID-19, this screening visit will be conducted remotely when needed. The 
brief in-person components will include signing consent forms if signature has not already been obtained. 
Consent signature will be obtained prior to the research procedures described below. Subjects will have the 
opportunity to ask questions. The informed consent process will have already occurred as described in this 
application. Procedures that will occur in person are body measurements, and a brief blood draw. If the 
phlebotomist is unable to draw blood after a few attempts, the participant will be asked if willing to return 
on a different day to complete their screening blood draw. Additional compensation will not be offered for 
returning for the blood draw. Physical exam for BWL participants may occur by phone and/or video call 
(Zoom), or in person if needed, and review of medical records by study physician. Actigraph will be given at 
Baseline visit. MRI safety screening will be confirmed; we will go through MRI safety screening form over 
the phone during initial phone screening, or possibly after the in person screening visit, but before Baseline 
visit. 
 
In non-COVID times, the following describes In-Person Screening: Consent (if not conducted ahead of time 
when approached in the clinic), medical history, measurements such as height, weight, blood pressure and pulse, 
temperature, blood draw. Subjects in the BWL group will have a physical exam by a study physician or study 
nurse. Research staff will confirm subject fit in MRI scanner by use of a mock scanner, or possibly a visit to the 
actual scanner, prior to which, MRI safety screening will be confirmed. Subjects will be given Behavioral 
Questionnaires (already approved questionnaires such as TFEQ, QEWP, PSQI, and the updated and new 
questionnaires which will be uploaded to Zipline. Subjects will be given Actigraph along with instructions and 
logs. Demonstrate dietary recall software. Visit will last 3-4  hours. 
 
Due to COVID-19, we have a plan for continuing some research procedures remotely while in-person procedures 
are temporarily halted. We may or will send questionnaires via email, a link to RedCap, or mail (we would provide 
self-addressed postage-paid envelopes for returning), and/or conduct over the phone for the following visit types:  
Interim visit, 6-month, 12-month and 18-month visits. We may or will continue to ask participants to wear 
Actigraphs and do dietary recalls (ASA24). We may also review medical history for any changes over the phone 
(only what we are already approved to collect as part of screening and follow-up visits). We will continue to pay 
participants the same way and same amount for each visit type for which remote procedures are completed as 
already described and approved in this IRB Protocol and on the consent form. We will communicate this 
information to research participants by phone or email.    
 
7-Day Lead-in period: Subject will wear Actigraph for 7 days and record information in logs provided at 
screening. Subject will receive 3 unannounced 24-hour dietary recalls via email 
) to 
report energy intake on a weekend and two weekdays. Time to complete the recalls is about 20-40 minutes each. 
For safety and convenience due to COVID, we may give the Actigraph to the subject at the Baseline and 6-month 
visits to wear following the visit and then return to us with provided postage paid envelope. They may also 
complete the ASA24 following the visits. For SWL (Surgical Weight Loss group), completing ASA24 before 
Baseline visit will be optional based on their surgery prep diet. The Actigraph may also be optional for SWL group 
at Baseline based on their surgery date (for example, Baseline visit is a day or two before surgery). Disinfection 
and cleaning of the equipment will meet the enhanced UW Environmental Health & Safety requirements 
described here
 
 
Baseline Visit: At UW SLU, lasts about 7-8 hours. Includes Indirect calorimetry, DXA, fasting blood draw, 
measurements such as weight, waist and hip, neck, blood pressure, heart rate and temperature, behavioral 
questionnaires, an MRI followed by a snack (milk, crackers, nut butter) equivalent to about 20% of the 
individual’s daily needs. A second MRI followed by buffet provided by Fred Hutch Human Nutrition Lab will 
occur. SWL and BWL subjects will be given the smart scale at this visit. SWL will have only the first MRI, no 
snack or buffet so the Baseline visit should take about 3-4 hours. 
 
 

 
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Interim Visit: HWC participants will not have this visit. The Smart scale will automatically transmit weights to 
research staff. Once the subject is close to 7% weight loss, the Interim Visit will be scheduled. Takes place at UW 
SLU, lasts about 3-4 hours. Includes measurements such as weight. Fasting blood draw, MRI and DXA scan. The 
time to 7–8% weight loss is anticipated to vary between the SWL and BWL arm. We anticipate this level of weight 
loss will be achieved by 75% in the BWL arm by 16–20 wk. and by most SWL participants within the first 2–6 
weeks. Subjects who don’t achieve 7-8% weight loss may still have this visit prior to the 6-month visit 
(approximately 5-month time point), or they may not be scheduled for this visit. Visits for normal weight controls 
will occur 3 mo. after their baseline visit. 
 
At approximately the 3 month time-point, (about 3 months after baseline visit), subjects will receive 3 
unannounced 24-hour dietary recalls (ASA-24) via email. Each dietary recall takes about 20-40 minutes to 
complete. 
 
6- Month Visit: Same as Baseline Visit. 
 
12- Month Visit and 18-Month Visits: Like Interim Visit in length and procedures. We will take waist and hip 
measurement and vitals at 18-month visit. 
 

 
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* MRI pre-meal, standardized meal, MRI post-meal and ad libitum buffet meal are for the HWC and BWL groups 
only. 
 
Below is a description of study procedures in more detail. 
 
Physical examination. Height, weight, and vital signs will be obtained. A physical examination will be performed 
by study physicians. We will add temperature to the vitals at In-Person Screening, Baseline, 6M, 18M. 
  
Body composition. Women of child-bearing potential will undergo a pregnancy test prior to receiving the DXA 
scan. Subject will change into scrubs. Certified DXA technicians will perform whole body scans for computing 
total body fat and lean mass (Lunar iDXA, GE Healthcare). CoreScan software will calculate visceral fat content, 
and its algorithm provides comparable results to abdominal CT scans. DXA takes about 30 minutes.  
 

 
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Questionnaires. Participants will self-report lifetime maximum weight and a detailed weight history (Participant 
Questionnaire). Descriptive measures will include the Three-Factor Eating Questionnaire (R-18), Questionnaire on 
Eating and Weight Patterns-Revised (binge eating disorder screening), Edinburgh Handedness Inventory, and 
Pittsburgh Sleep Quality Index, IPAQ, STOP-BANG, STAI-Trait, STAI-State, PHQ-9, Pregnancy history and 
Actigraph logs. Time to complete questionnaires should be about 15-20  minutes. At Baseline and 6-month visits 
subjects will be given VAS appetite ratings about every 30 minutes. Subjects will also be given taste and appeal 
ratings at Baseline and 6-month visits before and/or after meals and MRIs. An Exit Survey will be given to 
subjects at the end of the Behavioral Weight Loss Intervention. The survey will be uploaded to Zipline. We will 
administer questionnaires on paper, ipad, emailed questionnaire, or REDCap as needed to maintain safe distance 
and to comply with COVID related requirements. 
 
  
Physical Activity. Participants will wear accelerometers for 7 days (ActiGraph). Valid data will require at least 5 
days of >10 h of wear time. Average duration of sedentary time and light, moderate, and vigorous physical activity 
will be calculated using standardized software.  
 
Energy Expenditure. A handheld Indirect Calorimetry device (MedGem) will be used to measure energy 
expenditure. Prior to the procedure, fasting subjects will rest in a private room in the supine position for 30 min. 
Subjects will hold a disposable/replaceable mouthpiece for assessment of the amounts of O2 and CO2 in their 
exhaled breath to calculate resting energy expenditure (REE) and respiratory quotient. Data collection starts once a 
steady-state has been reached and continues for at least 20 min. 
 
Dietary Intake. Dietary recalls will be conducted using the Automated Self-Administered 24-hour Recall (ASA24) 
2016 system (National Cancer Institute, Bethesda, MD). Participants will complete 3 semi-randomly assigned 
dietary recalls (2 weekdays and 1 weekend day) per assessment. Here is a link to information about the ASA24 
followed by a brief description: 
 
 
The National Cancer Institute (NCI) created the Automated Self-Administered 24-hour (ASA24®) dietary 
assessment tool, a web-based tool that enables multiple, automatically coded, self-administered 24-hour recalls. 
 
Subjects will receive a tutorial from research staff about how to enter foods/drinks consumed. Subjects will be 
given an ID and password generated by ASA24. ASA24 records when and where meals were eaten and quantities 
consumed. Dr. 
 has used this dietary recall tool for two other studies (Kid’s Gliosis (reviewed by WIRB) and 
Brain Inflammation and Glucose Regulation).   
 
Dietary Intervention: The interventionist will administer a modified version of the Diabetes Prevention Program 
 with energy restriction following 
clinical guidelines for obesity management. Energy deficits to meet a goal of 10% weight loss over 6 mo. will be 
calculated.  Target ranges for macronutrients are 20–25% of total energy intake for protein, 25–35% for fat, and 
40–55% for carbohydrates. The intervention will start with about 2 one-on-one sessions of each participant with 
the registered dietitian/interventionist to explain the guidelines in detail and set personal goals for energy intake 
and physical activity. In weeks 2-12, participants will meet weekly in groups of ~12–15 participants with the 
registered dietitian/interventionist to cover material from the 12 modified DPP sessions. Groups will then meet 
approximately every other week to cover the remaining sessions of content (about 6 sessions). As in the DPP, 
participants will increase to 2.5–3 hours per wk. of moderate intensity physical activity. People participate in the 
intervention in person, however, arrangements can be made for a few sessions to be attended remotely (via phone 
or Zoom Meeting) if a participant will be out of town, or cannot attend for other reasons. All meetings for the 
behavioral intervention may or will occur via Zoom Meeting and/or telephone until further notice (due to Fred 
Hutchinson policies to reduce spread of COVID-19). This information will be shared by study staff and/or 
interventionists prior to scheduling meetings. The curriculum booklet may be given to the participant at the 
Baseline visit so they can refer to the material during Zoom meetings with the interventionist. 
 

 
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New intervention staff training will likely occur over the course of the study. We anticipate training of 1-3 
interventionists (appropriately credentialed Fred Hutch staff). Trainees will attend a few sessions to observe the 
interventionist, and for training purposes only, we plan to record (audio and/or video, or via Zoom Meeting) a few 
sessions. Prior to recording sessions, participants will be asked “on tape” if they consent to being recorded for 
teaching purposes.  
 
MRI and fMRI: Scans will be conducted at BMIC at SLU. MRIs on Baseline and 6-month visit days will take 
about 90 minutes for BWL and HWC and about 30 minutes for SWL. MRIs on other days will take about 30 
minutes. Subject will change into scrubs before entering the scanner. No contrast will be administered to subjects. 
Initial MRI safety screening will occur over the phone or in person prior to the Baseline Visit. We may ask a 
subject if they are willing to have an x-ray at their expense to confirm they are safe to scan should the MRI lab 
request it based on results of initial MRI screening. MRI screening will be repeated by study staff and MRI 
Technician. The DISC/BMIC lab will retain the screening form for 2 years with name and date of birth. Then the 
form will be destroyed.  
 
Once safety checked and changed into scrubs, the subject will lie on a flat moveable bench inside the magnet. 
They will be fitted with ear plugs and headphones. This provides hearing protection and ability to hear instructions 
and check-in with staff if needed during scanning. The head will rest in a helmet-like coil and made steady for 
clear images with soft padding. Respiration will be measured with a soft belt placed around the subject’s middle. 
The head piece has a mirror attached that reflects a screen placed at the end of the scanning bed. The subject will 
look at images or video (video is not a procedure; it is used if the subject would like to have something to focus on 
or distract them while they are in the scanner). The subject will be asked to lie still with their eyes open or to look 
at images during the whole time in the scanner.  The subject will leave the scanner and do some questionnaires, 
measures and consume the study snack and then return to the scanner for the second scan, which will be like the 
first scans. To limit the time participants are in small space in the MRI lab, we may omit questionnaires or change 
how we administer questionnaires following MRI. We may print on paper, load on ipad or REDCap. 
 
Blood draw: Screening and fasting blood draws will occur at SLU Lab. This procedure takes a few minutes, but 
there is occasionally a short wait to see the phlebotomist, so the procedure including wait time could be about 30-
45 minutes. Over the course of the study, about 157 mL of blood will be collected, plus an additional 30 mL may 
be collected at any visit up to 5 visits. The blood volume includes a tube of whole blood to be kept frozen for 
potential future use. This sample could be used to examine obesity related genetic markers that are known or 
emerge. 
• 
Screening: about 7 mL 
• 
Baseline: about 40 mL 
• 
Interim Visit: about 25 mL 
• 
6 Month: about 35 mL 
• 
12 Month: about 25 mL 
• 
18 Month: about 25 mL 
• 
An additional 30 mL may be collected at any of the visits (potentially an extra 30 mL x 5 visits) 
 
Study food (BWL and HWC groups only): A snack of peanut butter and crackers and milk (lactose-free milk and 
gluten free crackers will be available for subjects who don’t eat gluten or lactose) will be given to subjects at 
Baseline and 6-month visit. Subjects will be asked to consume the entire serving given to them in 15 minutes. An 
ad lib buffet will also be served after the second MRI at those visits. The buffet will be prepared by Fred Hutch 
Human Nutrition Lab and consist of a variety of foods. Subjects will be given 30 minutes to eat in a private food-
safe room.