Activity, Adiposity, and Appetite in Adolescents 2
Conditions: Obesity, Metabolic Disease, Insulin Sensitivity
Sponsor: Children's Mercy Hospital Kansas City

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SHORT TITLE: AAAA2 
 
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PROTOCOL TITLE: 
Activity, Adiposity, and Appetite in Adolescents 2 (AAAA2) 
PRINCIPAL INVESTIGATOR: 
Robin Shook 
Center for Children’s Health Lifestyles and Nutrition 
816-234-9443 
rpshook@cmh.edu 
 
VERSION NUMBER/DATE: 
04.26.2023 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
6.9.2021 
Initial IRB clarifications with revisions 
Y 
2 
07.19.2021 
Additional clarifications with revisions 
Y 
3 
01.27.2023 
Update insulin sensitivity protocol 
Y 
4 
04.26.2023 
Adding KUMC as a site 
N 
 
 
 
 
 
 
 

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Table of Contents  
1.0 
Study Summary ........................................................................................................ 3 
2.0 
Objectives ................................................................................................................ 3 
3.0 
Background .............................................................................................................. 4 
4.0 
Study Endpoints ....................................................................................................... 6 
5.0 
Study Intervention/Investigational Agent ................................................................ 7 
6.0 
Procedures Involved................................................................................................. 7 
7.0 
Data and Specimen Banking .................................................................................. 15 
8.0 
Genetic Analysis Information ................................................................................ 15 
9.0 
Sharing of Results with Subjects ........................................................................... 15 
10.0 Study Timelines ..................................................................................................... 15 
11.0 Inclusion and Exclusion Criteria ............................................................................ 15 
12.0 Vulnerable Populations .......................................................................................... 16 
13.0 Local Number of Subjects ..................................................................................... 17 
14.0 Screening and Recruitment Methods ..................................................................... 17 
15.0 Reimbursement, Payment and Tangible Property provided to subjects ................ 18 
16.0 Withdrawal of Subjects .......................................................................................... 19 
17.0 Risks to Subjects .................................................................................................... 19 
18.0 Potential Benefits to Subjects ................................................................................ 20 
19.0 Investigator Assessment of Risk/Benefits Ratio. ................................................... 20 
20.0 Data Management and Confidentiality .................................................................. 20 
21.0 Provisions to Monitor the Data to Ensure the Safety of Subjects .......................... 22 
22.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 22 
23.0 Compensation for Research-Related Injury ........................................................... 23 
24.0 Economic Burden to Subjects ................................................................................ 23 
25.0 Permission/Assent/Consent Process ...................................................................... 23 
26.0 Process to Document Permission/Assent/Consent................................................. 24 
27.0 Setting .................................................................................................................... 25 
28.0 Resources Available............................................................................................... 26 
29.0 Multi-Site Research ............................................................................................... 26 
30.0 International Research ........................................................................................... 28 
 
 
 
 
 

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1.0 
Study Summary 
 
Study Title 
Activity, Adiposity, and Appetite in Adolescents 2 
(AAAA2) 
Study Design 
Cross-sectional 
Primary Objective 
To examine the association between physical activity and appetite 
control in adolescents, with metabolic function serving as a 
mediator. 
Secondary 
Objective(s) 
n/a 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
n/a 
IND/IDE #  
n/a 
Study Population 
Adolescents age 14-17 (Tanner Stage III-V) 
Sample Size 
Approximately 60 (40 completing the entire protocol) 
Study Duration for 
Individual 
Participants 
Approximately 35 days (this can be extended to 
accommodate participant’s schedules) 
Study Specific 
Abbreviations/ 
Definitions  
RD – registered dietitian, MS – measurement session, EE – 
energy expenditure, EI – energy intake, DXA – dual energy 
X-ray absorptiometer, EGC – Hyperinsulinemic-Euglycemic 
Clamp, CRF – Cardiorespiratory fitness , RMR – resting 
metabolic rate, TEF – thermal effect of feeding, CEQ – 
control of eating questionnaire, VAS – visual analogue scale, 
FM – fat mass, FFM – free fat mass, CCHLN – Center for 
Children’s Healthy Lifestyles and Nutrition,  CRF – 
cardiorespitory fitness 
 
 
2.0 
Objectives 
2.1 
To examine the association between physical activity and appetite control in 
adolescents, with metabolic function serving as a mediator. 
2.2 
Hypothesis 1: Appetite, as measured subjectively, via self-reported hunger 
and palatability responses, and, objectively, via satiety/appetite hormones 
(glucose, insulin, ghrelin, and leptin) responses following a standardized 
meal and calories consumed during ad libitum meal, will be altered in 
sedentary vs. active adolescents, regardless of body weight status. 
Hypothesis 2: Reduced metabolic function, defined as low insulin sensitivity 
and metabolic flexibility, measured by hyperinsulinemic euglycemic clamp 
and indirect calorimetry, will be associated with poorer appetite control and 
physical inactivity as defined in Hypothesis 1. 

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3.0 
Background 
3.1 Overall Scientific Premise- Weight gain is determined by energy balance status. 
Data from the National Health and Nutrition Examination Survey (NHANES) 
indicate that 16.9% of US children and adolescents are classified as obese (BMI > 
95th percentile) and 31.8% of youth are either overweight or obese (BMI > 85th 
percentile) [1, 2]. This is driven, in part, by declines in physical activity that begin 
around age 15 years for boys and age 10-13 years for girls [3], with only 27% of 
12-17 year olds obtaining 60 minutes of moderate to vigorous physical activity [4]. 
Healthy eating follows a similar same age-related decline, but at an even lower 
level with only 10% eating five servings of fruits/vegetables per day [5]. At the 
most basic level, obesity is the result of a mismatch between the amount of calories 
consumed and the amount of calories expended over an extended period of time. In 
reality a variety of known and unknown systems involving complex relationships 
between biological, physiological, psychosocial, and environmental factors [6, 7] 
influence the components of energy balance [8, 9]. Clearly, if effective prevention 
and treatment strategies currently existed based on a complete understanding of 
energy balance, worldwide levels of obesity would not have reached pandemic 
proportions [10].  
Physical Activity is Associated with Appetite Control.  The concept of 
dysregulation of appetite at low levels of 
physical activity is not new, with Mayer and 
others [11, 12] exploring the topic in a series of 
studies in the 1950s. It was observed in mice, 
rats, and humans [13-15] that energy intake 
only increased proportionally with energy 
expenditure within a certain range of physical 
activity, described by Mentor Dr. John Blundell 
[16] as the ‘zone of regulation’ (Figure 2). In 
contrast, when activity levels are low 
(inactivity), the relationship between intake and 
expenditure is uncoupled and in the “non-
regulated zone”, resulting in energy imbalance.  
3.2 Recent work has confirmed the links between elevated energy intake and appetite 
dysregulation at low levels of physical activity.  We (Shook and Blundell, among 
others) recently completed an analysis of energy balance among adults (N=421, 
mean age=28 years) over a 12-month period which included grouping participants 
by quintiles according to their level of objectively measured physical activity [17]. 
First, we observed increasing levels of physical activity in quintiles 2-5 
corresponded with increases in energy intake, indicating energy balance. However, 
individuals in the lowest quintile of physical activity had a higher energy intake 
than groups 2 and 3, despite expending less energy (Figure 1). Second, individuals 
in this lowest quintile of physical activity had higher levels of disinhibition and 
preference for savory foods compared to their more active peers. Third, individuals 
with low levels of physical activity experienced the largest gains in fat mass, 
resulting in 3.8 higher risk of gaining clinically significant (>3%) amounts of fat 

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mass over 1-year. Our findings have since been replicated by others [18-20]. Taken 
together, our results support the hypothesis proposed by Mayer et al. [15] and 
others that a low level of physical activity is a risk factor for weight gain via a link 
to not only reduced energy expenditure but also dysregulated appetite control which 
leads to gains in fat mass. However, 
these findings raise important 
unanswered questions. What are the 
biological mechanisms by which 
physical activity influences appetite? 
What is the temporal relationship 
between physical activity and 
appetite control? Are the links 
observed in adults also present in 
adolescents?  
Evidence that Metabolic Function 
may 
be a Mediator. As noted by Blundell 
[21] 
and by others [22], several clues point to metabolic function as a mediator in the 
relationship between activity status and appetite control. First, resting substrate 
metabolism has been shown to partially explain post-exercise eating behavior [23, 
24] and be predictive of long-term weight gain [25-27]. We have previously shown 
that high utilization of stored carbohydrates and low utilization of stored fat 
(elevated respiratory quotient (RQ)) predicts weight gain 1 year later in healthy 
adults (Figure 4) [28], and partially explains unexpected weight gain among those 
who increased their  MVPA over 1 year [29]. Second, blunted hepatic and skeletal 
muscle metabolism has been linked to increased energy intake and subsequent 
weight gain. Dr. John Thyfault recently observed greater food intake and short-term 
weight gain following a 3-day western diet in rodents with chronically reduced 
hepatic fatty acid oxidation (via low aerobic capacity) and mitochondrial respiratory 
function [30]. His group has recapitulated these findings in mice with liver-specific 
reductions in mitochondrial FAO due to PGC-1α heterozygozity (Morris et al., in 
review) (Figures 5 & 6). Third, there is evidence that manipulating substrate 
metabolism has causal effects on energy balance. For example, stimulating liver 
specific glucose or fat utilization can prevent weight gain [31, 32], while inhibiting 
glucose or fat oxidation and subsequent declines in hepatic ATP increases food 
intake via vagal 
afferent signaling 
to the central 
nervous system  
[33-36]. We 
believe that 
sedentary 
behavior induces 
negative changes 
in substrate 
metabolism that 
results in the 
Figure 5. LPGC1a+/- mice have A) reduced hepatic mitochondrial complete 
FAO and B) ADP-couple respiration of palmitoyl-carnitine which is associated with C) 
increased weight gain following 3-day western diet 
Figure 6. LPGC1a+/- mice fed high fat diet for 3-days have A) increased food intake 
compared to low fat diet. 3-days of WD in LPGC1a+/- mice results in altered feeding 
patterns: B) food intake per event, C) number of feeding events.  
Figure 4. High RQ (low fat oxidation) is associated 
with increases in fat mass after 1 year. 

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metabolic phenotype described in this section, but it is unknown if this is associated 
with appetite dysregulation and subsequent weight gain. Conversely, it is well 
known that increasing physical activity obtained through structured exercise will 
improve systemic metabolic function [37-39], but it is not clear if this will also 
improve appetite regulation.  
Appetite Control in Adolescents is Unknown. Despite a growing body of evidence 
in adults that physical activity plays a role in mediating appetite control, little work 
has been performed in adolescents. Most studies in adolescents consists of appetite 
measures performed as secondary outcomes in studies with possible confounding 
factors (e.g. underlying disease risk) [39-41]. Observational data suggests higher 
levels of obesity are associated with dysregulated appetite as defined by satiety and 
responses to food cues [42] and higher energy intake despite lower levels of 
physical activity [43]. A smaller number of clinical trials have found that exercise 
trials in adolescents improves biomarkers of appetite control [44]. Of particular note 
is an eight-month aerobic intervention among OW/OB adolescents, with the effects 
of exercise isolated since there were no changes in body weight (but improvements 
in body composition) during the study [37]. Hormones peptide YY and resistin 
decreased following completion of the intervention, suggesting improved regulation 
of appetite with higher levels of physical activity. However, assessments in each of 
these studies were limited to fasted measurements, not as part of a more 
methodologically rigorous and informative meal challenge. Taken together, a small 
number of studies in adolescents support the scientific premise that physical activity 
and appetite are associated. What is not clear is strength of the association between 
the activity and appetite, the role of metabolism in this relationship, nor the effects 
of a structured exercise regimen in this association.    
Challenges to Existing Paradigms. The status quo as it pertains to appetite control 
emphasizes the role of peripherally derived signals mediating energy intake in the 
CNS [Figure 7 - e.g. insulin and ghrelin mediate appetite through pathways 
centered in the hypothalamus [45-47]]. This concept is supported by a strong body 
of evidence, dating from as far back as 50 years, including the discovery of leptin in 
1994. However, it has been argued that this paradigm primarily accounts for the 
inhibition of eating as opposed to the drive of eating. An alternative approach, 
centered on the concept of energy balance, postulates that daily energy expenditure 
regulates appetite (Figure 7). It has been put forth by Mentor Blundell, and adopted 
by others [20, 22], that overall appetite is regulated through three components: 1) a 
tonic (i.e. constant) drive for food driven by energy demands; 2) tonic inhibition 
from signals of energy storage (e.g. leptin); 3) episodic (i.e. response-initiated) 
signals from the periphery in response to food. This new approach emphasizes the 
contribution of physical activity and energy expenditure on both the tonic excitatory 
drive to eat and episodic regulation of fasting hormones (ghrelin) and satiety 
hormones (GLP-1 and PYY) [19, 48, 49]. Importantly, this new formulation 
recognizes the role of resting metabolic rate [16] and fat free mass on appetite 
control. We extend this theory to include metabolic function, as there is evidence 
that it is also associated with eating behavior (see section A.2.), pointing to a 
specific biological mechanism by which appetite regulation may occur. 

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3.3 New Approaches. The proposed research is innovative because it shifts beyond the 
tonic inhibition approach, to include the regulation of appetite via energy 
expenditure and metabolic function. Our preliminary studies (see sections 2.1-2.5) 
indicate that energy intake and disinhibition become dysregulated at low levels of 
physical activity, resulting in 3.8 fold greater fat mass 1 year later [50]. We will 
extend previous findings in adults to adolescents, a previously unexamined 
population in regard to this concept. Additionally, we have expanded upon previous 
studies in the proposed project by exploring plausible metabolic mechanisms that 
underlie appetite dysregulation at low levels of activity. By completing this work, it 
is our expectation that we will have described the independent effects of physical 
activity and obesity on appetite and energy metabolism in adolescents. 
4.0 
Study Endpoints 
4.1 
The primary study endpoint is the enrollment of 10 participants per study 
arm (normal weight/active, normal weight/sedentary, overweight, 
obese/active, and overweight, obese/sedentary).  
4.2 
There are no safety endpoints for this study.  
5.0 
Study Intervention/Investigational Agent 
N/A – no intervention/investigational agent 
 
6.0 
Procedures Involved 
 

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6.1 
This is a cross-sectional study design (see above figure). The study team aims to 
assign N=10 participants to each arm of the study (normal weight/active, normal 
weight/sedentary, overweight, obese/active, and overweight, obese/sedentary). 
6.2 
Participants who fall into the overweight/obese category (~20) will also be recruited 
for the AAAA2 – Exercise study (AAAA2 study with an intervention and post 
intervention tests), which includes the same testing as AAAA2. The AAAA2 - 
Exercise study will only include those with a BMI percentile from the 85th to 99th 
percentile. It also has an exercise intervention (same as the BATE study), which 
50% of study participants will be randomly assigned to. All 3 visits (measurement 
session 1, measurement session 2 and insulin sensitivity visit) will be completed 
before and after the exercise intervention. For those participants that complete 
testing in the AAAA2 study and are interested in the AAAA2 – Exercise study, 
their AAAA2 data will be used as baseline data in the AAAA2 - Exercise study. 
They will then consent for the AAAA2 - Exercise study and start their exercise 
intervention, or wait until their follow-up visits.  
Orientation Session: 1 hour. The orientation session will serve as a visit to explain the details 
of the study, with example images of what tests will be completed.  P/A/C documentation will 
also be completed at this visit if they decide to participate. If a participant and parent opt for in-
person orientation, after consent, their height, weight and blood pressure will be collected to 
classify each participant into an arm of the study. If a virtual orientation is chosen, height and 
weight will be reported from them, according to their most recent measures. Following P/A/C for 
both in-person and virtual orientation, the Contact Information Questionnaire will be 
completed. After completion of the orientation session, the parent and subject will be instructed 
to complete the Medical History and Demographics Questionnaire prior to the first 
measurement session visit. This questionnaire will be sent through a RedCap link.  
Measurement Session 1: 5.0-6.0 hours. This study visit will take place at the Don Chisholm 
Center in the morning (<9:00am) following an overnight dietary fast. This study visit will be 
conducted to assess appetite control and relevant variables under laboratory conditions. The 
measures conducted in this visit are provided below 
• Surveys 
• TFEQ 
• CEQ 
• VAS Pre-Meal 
• VAS Post-Hedonic 
• VAS 
• Anthropometry and Body Composition via DXA. 
• Fat mass (FM) and fat-free mass (FFM) will be measured using a 
whole-body dual energy X-ray absorptiometer (DXA, Lunar DPX 
system, version 3.6). 
• Waist and Hip Measurements. Waist measured in centimeters, two 
inches above the umbilicus at skin level, at the end of a normal breath 
expiration, with arms relaxed at sides. Hip measured in centimeters at the 
maximum circumference of the buttocks, with arms relaxed at the sides. 

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• Fixed/Ad libitum Meals.  Appetite (see below) will be assessed following 
a fixed standard breakfast (40% of RMR, composed of 55% carbohydrate, 
15% protein, 30% fat). Food intake (total kcals) will also be assessed 
using an ad libitum meal served three hours after the fixed meal. 
Participants will be instructed to eat until comfortably full and informed 
that they can request more of the meal at any point.  
• Each plate of food will be weighed before and after serving, without the 
subjects’ knowledge. 
• Appetite and Eating Behavior Subjective assessment of hunger and 
palatability will be completed using self-rated visual analogue scales 
(VAS) [51], with each scale consisting of a 10-cm long line separating 
statements such as “not at all hungry” and “extremely hungry”. [VAS 
tools are widely used to assess health conditions and show good test-retest 
reliability [52], especially in within-subject repeated measures study 
designs [53].] Perceptions of dietary restraint, disinhibition, and hunger 
will be measured during each measurement session using the Three Factor 
Eating Questionnaire (TFEQ) [54]. The Control of Eating Questionnaire 
(CEQ) will be used to assess hunger, fullness, cravings, the desire to eat 
certain types of foods, and the ability to resist urges to eat [55]. Objective 
assessment of appetite will be completed using blood samples taken from 
an indwelling catheter, and analyzed for episodic regulation of the 
following fasting and satiety hormones: glucose, insulin, leptin, ghrelin, 
glucagon-like peptide 1 (GLP-1), and peptide YY (PYY). All samples will 
be mixed a standard preservative (400 µL of 10,000 KIU aprotinin), 
centrifuged, the plasma divided and stored in -80°C freezer until later 
analysis.  
• Resting Metabolic Rate.  Resting metabolic rate (RMR) will be measured 
via indirect calorimetry using a ventilated hood and open-circuit system 
metabolic cart (ParvoMedics, Salt Lake City, Utah) following a standard 
protocol [56]. 
• Thermic effect of feeding (TEF) will measure the energy expenditure 
resulting from digestion following the fixed meal using the ventilated 
hood.  
 
Continuous, Free-living Home Assessments of Energy intake/expenditure: 7 days 
between Measurement Session 1 and Measurement Session 2.   
• The free-living assessment period is defined as the 7 days between 
Measurement Session 1 and Measurement Session 2. During these 7 
days, subjects will be completing two energy intake/ expenditure 
assessments while going about everyday life activities at home. These 
assessments are explained in proceeding bullets.  
• Energy intake will be assessed during the free-living 7-day assessment 
period via standardized 24-hour dietary recalls. Energy intake will be 
assessed using three dietary recalls occurring on randomly selected non-
consecutive days over each 7-day free-living assessment period 

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(including at least one weekend day) to minimize preparation that could 
bias recall, by a team of experienced staff employing a multi-pass 
approach, which utilizes prompts to reduce food omissions and 
standardizes the interview methodology.  
• Physical activity and energy expenditure will be estimated using two 
physical activity monitors (Actigraph GT9X Link, Actigraph Inc., and 
ActivPAL, PAL Technologies), which assesses movement using tri-axial 
accelerometry. The monitors themselves are not being studied as a part of 
this protocol, and while they do not have 501(k) documents, the devices 
used in this study are not considered to be more than minimal risk. 
 
Measurement Session 2: 2.0 hours. This study visit will take place at the Don Chisholm 
Center. This visit will include a DXA scan, mitochondrial function testing via NIRS, and 
cardiorespiratory fitness testing (CRF): 
• Body Composition via DXA: 
▪ Fat mass (FM) and fat-free mass (FFM) will be measured using a whole-
body dual energy X-ray absorptiometer (iDXA, Lunar DPX system) with 
the participant dressed in surgical scrubs and in bare feet.  
• Grip Strength Testing:  
▪ Grip strength will be assessed using a handheld dynamometer. The 
participant will hold the device in one hand in line with the forearm at the 
level of the thigh, away from the body. 
▪ The participant squeezes the handgrip dynamometer as hard as possible 
without holding their breath. Neither the hand nor the dynamometer should 
touch the body. The test is repeated twice in each hand and scored as the 
sum of the highest measurement from each hand.  
• Mitochondrial Function via Near-Infrared Spectroscopy 
▪ Assessment of skeletal muscle oxidative capacity using near-infrared 
spectroscopy (NIRS) will be performed. The specific protocol used to 
measure skeletal muscle oxidative capacity was initially described by Ryan 
et al (2014). An ISS Medical (Champaign IL, USA) Dual-Channel 
OxiplesTS advanced NIRS device that uses Frequency Domain technology 
to provide an absolute determination of oxy[heme] and deoxy[heme] in 
various tissues will be used. This device uses 8 near infrared lasers emitting 
690nm to 830nm wavelengths which penetrate the skin without damage and 
are reflected to a Hamanatsu R928 detector. The instrument is controlled 
through a laptop computer and specialized software package (both provided 
by ISS Medical). 
▪ The NIRS muscle probe will be positioned on the skin longitudinally above 
the belly of the vastus lateralis muscle of the right leg, halfway between the 
patella and the hip. The probe will be secured using double-sided adhesive 
tape and Velcro straps around the thigh. After device calibration and a 30-
minute warm-up period, blood pressure cuff designed for the thigh (specific 
size will be dependent on the patient) will be placed proximal to the NIRS 
probe as high as anatomically possible. The inflation of the cuff will be 

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controlled with a rapid-inflation system set to a pressure between 
>200mmHg, powered with a 15-gallon air compressor. 
▪ Participants will perform short duration (10-15 second) voluntary isometric 
contractions of the quadriceps to increase muscle oxygen consumption. 
Following voluntary contraction, recovery kinetics of the muscle will be 
measured using a series 10 transient arterial occlusions with timing of 5 
seconds on – 5 seconds off; followed by a series of another 10 transient 
arterial occlusions with timing of 10 seconds on – 10 seconds off. Post each 
occlusion, the rate of change (slope) in the decline in deoxy[heme] will be 
calculated. The resting procedure will be performed twice with results 
averaged. 
• Thigh Circumference and Skinfold Measurement 
▪ To identify optimal NIRS probe placement, mid-thigh circumference will 
be measured using the right thigh at the midpoint between the inguinal 
crease and the proximal border of the patella. 
▪ Skin and adipose tissue thickness will be measured at the site of the NIRS 
probe using skinfold calipers. The technician will ‘pinch’ the skin and 
adipose tissue with their thumb and fore finger and measure the tissue 
thickness with a set of calipers.  
• Cardiorespiratory Fitness Testing: 
▪ Submaximal oxygen consumption (fitness test) and maximal oxygen 
consumption will be assessed using an indirect calorimetry system with 
mouthpiece via standard protocols using a treadmill. Prior to the start of the 
test, resting blood pressure, heart rate, and oxygen saturation will be 
assessed using an automated vital signs monitor.  
▪ The submaximal exercise test will consist of walking at two speeds for five 
minutes each estimated as ‘light’ and ‘moderate’ intensity by the research 
technician. Following a five-minute break, the maximal test will be 
performed using the Bruce protocol. The Bruce protocol is the most widely 
used fitness testing protocol used in the US and consists of a series of three-
minute stages that gradually increase the speed and grade of the treadmill. 
The majority of individuals reach volitional fatigue 9-12 minutes into the 
test. During both the submaximal and maximal tests, heart rate will be 
measured via monitor (Polar) and gas exchanged will be measured using 
indirect calorimetry (TrueOne, ParvoMedics, Parvo, UT, USA). Following 
completion of the test, blood pressure, heart rate, and oxygen saturation will 
be assessed using an automated vital signs monitor to ensure an appropriate 
post-exercise response. 
• Muscular Strength Testing: 
▪ Muscular strength will be assessed with a one-repetition maximum (1-RM) 
test for the chest press and seated leg press using weight stack equipment 
(Paramount, St. Louis, MO, USA) following the protocol used by Co-I 
White [57, 58]. Resistance will be progressively increased by 2.5-20 kg 
until a maximal lift is achieved with a full range of motion within four 
attempts (3–5 min rest between trials). Muscular strength will be calculated 

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as the sum of the 1-RM scores for the bench and leg press per kg of body 
weight. 
 
Insulin Sensitivity Visit: 5 hours. This study visit will take place at University of 
Kansas Medical Center Clinical and Translational Science Unit (KUMC CTSU) 
located on the Fairway campus. This visit will involve baseline blood samples and 
blood samples taken throughout the insulin sensitivity test.  
• Hyperinsulinemic euglycemic clamp.  
o The hyperinsulinemic-euglycemic clamp is the gold standard for 
assessing insulin sensitivity as stated by the World Health 
Organization. It allows the insulin levels to be ‘clamped’ at a 
constant state so that insulin stimulated by physiological measures 
can be assessed. Insulin sensitivity can be determined by the 
amount of glucose that is infused to maintain euglycemia. The 
higher the amount of glucose that needs to be infused while insulin 
is clamped, the more insulin sensitive the subject is. 
o The hyperinsulinemic euglycemic clamp will be performed at the 
University of Kansas Medical Center Clinical and Translational 
Science Unit (KUMC CTSU), located at 4350 Shawnee Mission 
Parkway, Suite 3220 Fairway, Kansas. The CTSU contains 17 
clinic rooms, 2 cognitive testing rooms, and open workspaces for 
up to 5 visiting study coordinators. The CTSU’s infusion center 
has 11 infusion bays supported by two nursing stations and activity 
in the center has steadily grown. The center also supports research 
infusions and intensive and complex metabolic research 
assessments such as hyperinsulinemic-euglycemic clamps (see 
Morris et al. 2016). There is a CTSU medical monitor available for 
Adverse Events. The CTSU medical monitor is contacted when 
there is an urgent, medical concern / AE with the participant; The 
medical monitors are MD’s or NP’s / APRN’s (aka Advanced 
Practice Registered Nurse). NOTE: This is in addition to the study- 
specific DSMB.   
o Participants will arrive fasted (12-hours overnight), and one 
catheter will be inserted into an antecubital vein of one arm to 
infuse insulin and 20% dextrose, and another catheter will be 
inserted into a contralateral vein in the hand/arm for blood 
sampling. The participant will rest quietly and we will collect 3 
baseline blood samples to establish baseline glucose levels. If 
baseline values are <60 mg/dL the procedure will not continue. 
Once baseline assessments have been completed,  a primed 
continuous infusion of regular human insulin plus albumin will be 
administered at a rate of 40 mU·m2 body surface 
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maintain euglycemia to match baseline levels (expected 90-100 
mg/dL). Blood glucose measurements will be completed every 5 
minutes for determination of glucose infusion rate using a Nova 
Statstrip handheld glucometer and YSI analyzer as needed.  
o After approximately 90 minutes of acclimatization, a 30-minute 
data collection period will occur. Insulin sensitivity will be 
determined as average glucose concentration and glucose infusion 
rate during this 30-minute period of euglycemia (defined as 
glucose concentration and glucose infusion rate coefficient of 
variation <10%).  
o After this 30-min period, A 60-minute recovery period begins. 
Insulin infusion is stopped, and glucose infusion continues at the 
last rate for 30-min to prevent hypoglycemia. Glucose infusion is 
stopped 30 minutes into recovery if blood glucose levels remain at 
acceptable levels.    
o Participants will be provided a full lunch meal (e.g., sandwich, 
potato chips, drink) following the cessation of insulin infusion to 
minimize the chances of hypoglycemia. Participants will be 
provided with a 20 mEq potassium pill to take with food. In rare 
instances hypokalemia can occur resulting from hyperinsulinemia 
and increased glucose disposal. Potassium supplementation helps 
prevent this from occurring. 
o Following the cessation of glucose, all participants will remain 
under observation at the CTSU for the final 30 minutes of recovery 
to monitor for hypoglycemia.  
o Participants can be released if participant is asymptomatic and 
blood glucose levels are acceptable at the end of the observation 
period.  
o Blood is drawn from a hand/arm vein after the hand/arm has been 
placed under an electric blanket and this technique is called 
arterialization, as it makes the blood in the vein have similar 
characteristics to that flowing in the artery by dilating the vessels 
in the arm. This is a well-accepted technique that allows us to 
avoid performing an arterial IV placement. The hand/arm will be 
placed under the blanket for the entire testing procedure.  
o Insulin Mixing Procedures: The CTSU Investigational Pharmacy 
(located onsite) will store the insulin and albumin. The unused 
insulin and albumin will be returned to the pharmacy after each 
study. CTSU nurses will mix the insulin, albumin, and saline. For 
the mixing procedures, 2 mL of human albumin is injected into a 
bag of 250 mL sterile saline and gently inverted to mix the 
solution. Using an insulin syringe, 1.25 mL of insulin is added to 
the albumin/saline mixture and gently inverted to mix the solution. 
o The mixing of insulin with albumin is essential to minimize the 
binding of insulin to the saline bag, as well as the catheter tubing. 
This procedure for mixing the infusate was described in the initial 

myIRB#: STUDY00001808 
 
SHORT TITLE: AAAA2 
 
Page 14 of 31 
 
report of the hyperinsulinemic-euglycemic technique (DeFronzo et 
al, 1979) using blood rather than albumin and is still utilized by 
labs that perform the hyperinsulinemic-euglycemic clamp. We are 
using albumin in this study to prevent the possibility of clotting 
associated with the use of blood. 
6.3 
Data collected during the study includes self-report survey data (see myIRB 
local documents) as well as DXA, RMR, VO2, TEF, NIRS, and blood test 
results. Anthropometric measurements such as height and weight will also 
be collected. Dietary recall data and activity monitor data will be collected 
during the free-living assessment period (sample output available on local 
documents). Finally, insulin sensitivity will be determined through the 
Hyperinsulinemic-Euglycemic Clamp procedure.  
6.4 
There are no plans for long-term follow-up beyond study completion. 
6.5 
Standards and Safety of Participants 
• 
All devices used in the study are FDA approved (DXA, RMR hood 
machine, NIRS, ActiGraph, ActivPAL, etc.). 
• 
This study involves DXA scans –Female participants of child-bearing 
age are required to complete a pregnancy test before DXA scan.  
• 
A nurse will perform any blood draws and all study staff assigned to 
perform lab procedures or RQ will be specifically trained to work with 
that equipment. This is training that is above and beyond the regular 
research CMH or standard research education. 
• 
Appetite assessments: Blood will be collected via an IV catheter over 
8 time points) over a period of 3 hours. Approximately 36mL (two 
samples at time 0, one sample at all other time points, 9 samples x 4 
mL= 36 mL= 1.22 oz) of blood will be collected. 
• 
Euglycemic clamp: Three baseline blood samples will be collected at 
the onset of the session to determine baseline glucose and insulin 
levels. The total amount of blood collected at baseline will be 
approximately 9 mL (3 samples x 3 mL/sample= 9 mL). Blood will be 
sampled every five minutes during the clamp procedure to monitor 
glucose levels. The total amount of blood collected to monitor glucose 
will be approximately 36 mL (36 samples x 1 mL/sample = 36 mL). 
Every 15 min we will also collect blood samples to store for 
assessment of insulin at study completion. The total amount of blood 
to assess insulin will be approximately 24 mL (12 samples x 2 
mL/sample= 24 mL). During recovery, blood glucose is assessed every 
10 minutes and insulin once. The total amount of blood collected 
during recovery is 8 mL (6 glucose samples x 1 mL= 6 mL; 1 insulin 
sample x 2 mL= 2 mL).  
• 
Total amount of blood collected during the entire clamp procedure is 
approximately 77 mL (9 mL + 36 mL + 24 mL + 8 mL) or 15.6 
teaspoons/2.6 ounces.  

myIRB#: STUDY00001808 
 
SHORT TITLE: AAAA2 
 
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• 
The amount of blood is within the allowable amounts to be collected 
for research purposes.   
• 
No subjects will be less than 16.5 kg 
 
7.0 
Data and Specimen Banking 
7.1 
Samples will be stored in the CCHLN biochemistry lab 
7.2 
Study ID, birth year, visit date only 
7.3 
CM research only, for the purposes of this study only 
7.4 
N/A – samples not retained for long-term research. 
8.0 
Genetic Analysis Information 
N/A – no genetic analysis 
 
9.0 
Sharing of Results with Subjects 
9.1 
At the conclusion of the study, a report with the participant’s study results 
will be shared with each participant. Results will include:  
• 
Height and weight 
• 
Blood pressure values 
• 
Fitness percentile 
• 
Resting metabolic rate 
• 
Activity monitor data such as steps per day 
• 
Two body composition scans with bone mineral density 
• 
Grip strength 
 
10.0 Study Timelines 
10.1 Describe: 
• 
Individual participation in the study will last approximately 35 days, 
but this time period can be extended to accommodate participant’s 
schedules. 
• 
Recruitment and data collection will last approximately 18 months. 
 
11.0 Inclusion and Exclusion Criteria 
11.1 
 
Inclusion Criteria 
• Males (~50%) and females (~50%) 
• Age 14-17 (Tanner Stage III-V, as determined via self-assessment) 
• Non-smoking 
• Not currently involved in any other research study 

myIRB#: STUDY00001808 
 
SHORT TITLE: AAAA2 
 
Page 16 of 31 
 
• Willing to give informed consent to participate 
 
Exclusion Criteria 
• Age <14 or >18 at time of enrollment  
• Restrained eater (>13 on the restraint section of the three-factor eating 
questionnaire; Current/past diagnosis of an eating disorder. 
• Self-reported medical conditions (including, but not limited to, diabetes, Crohn’s 
disease, etc.) that may affect adherence to the protocol, exercising safely, or alter 
metabolism 
• Taking medications know to affect metabolism (e.g. thyroid medication, β-
blockers, or stimulants). 
• Gave birth in the past 12 months or <6 months post-lactation. 
Individuals who are not yet adults (infants, children, teenagers) will be included in this 
study (teenagers age 14-17). 
 
12.0 Vulnerable Populations 

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☐ Children/Minors (under 7 years of age) 
☒ Children/Minors (7-17 years of age) 
☐ Neonates (infants less than 30 days old) 
☐ Neonates of Uncertain Viability (infants less than 30 days old) 
☐ Non-Viable Neonates (infants less than 30 days old) 
☐ Wards of the State 
☐ Fetuses 
☐ Pregnant Women  
☐ Adults with impaired decision-making capacity 
☐ CM Employees 
☐ CM Students/Residents/ Fellows 
☐ Economically or Educationally Disadvantaged Persons 
☐ Prisoners 
 
• This study involves children who are not yet adults. The study will be 
explained to them at the study visit as well as during the informed consent 
discussion.  
• The research involves no more than minimal risk to the subjects. 
• HRP-416 - CHECKLIST - Children has been reviewed. 
 
Local Number of Subjects 
12.1 This study involves four cohorts: normal weight/inactive, normal 
weight/active, OW,OB/inactive, and OW,OB/active. The goal is to 
accrue 10 participants in each cohort for a total of 40 study 
participants. We anticipate the need to enroll about 60 total 
participants to account for screen fails and dropouts. 
12.2 We expect to make send our study letter to 2,000 potential 
participants, screen about 900, and enroll around 60, to get our final 
enrollment goal of 40. This is based off our previous AAAA 
submission with similar inclusion/exclusion criteria. 
12.3 N/A – no chart review beyond what is required for screening. 
13.0 Screening and Recruitment Methods 
13.1 Participants will be recruited from previous Energy Balance research 
studies, from a recruitment list generated by CMH MIT, and a 
recruitment list generated from KUMC pioneers/frontiers. 
Recruitment letters and flyers will be mailed to the parents of 
potential participants from the above recruitment methods. 

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Additional recruitment methods include social media resources, the 
CCHLN website, dissemination of the study flyer to partner 
departments and institutions, and articles posted on the Scope using 
Daily E-News at Children’s Mercy. 
13.2 Participants will be recruited from CMH, KUMC, and the 
community. 
13.3 When available, study staff will use previous contact with Energy 
Balance research participants (or potential participants that stated 
they were interested in other opportunities), CMH MIT generated 
data or KUMC generated data to pre-screen (or identify) potential 
participants. When not available, study staff will use a Redcap 
screener to verify eligibility. 
13.4 
Study staff will record, and request (from resources such as CMH MIT) 
only the minimum necessary identifiable data for the purposes of contacting 
participants prior to ICF and pre-screening.  We are requesting a Waiver of 
HIPAA Authorization for recruitment and screening purposes only. Minimum 
necessary PHI on non-participants will only be kept until completion of 
enrollment. 
13.5 We may disseminate the study flyer to other departments for the 
purposes of recruitment (Teen clinic, weight management clinic, 
etc). 
13.6 Individuals will be contacted a maximum of 3 times (including 
voicemails), when following up after mailing a study letter. 
14.0 Reimbursement, Payment and Tangible Property provided to 
subjects 
 
14.1 Participants will be paid via pre-paid debit card. Participants will be paid 
when activity monitors are returned at the DXA/CRF visit $175, and another 
$125 at the insulin sensitivity visit.  
 
14.2 Participants will be paid $5 for each visit they attend as a travel 
reimbursement, with a max possible travel compensation of $15 to be paid 
at the completion of the study.  
 
Payments will be administered as follows:  
Measurement Session #2: $175 for study procedures 
Insulin Sensitivity Visit: $125 for study procedures, maximum of $15 ($5 
per visit) for travel reimbursement 
Total Compensation: $300 for study procedures plus a maximum of $15 for 
travel reimbursement totaling a maximum compensation of $315.  
14.3 N/A – no tangible property given 

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15.0 Withdrawal of Subjects 
15.1 Non-compliance with the protocol. 
15.2 The study team will attempt to contact the participant for the 
purposes of determining a reason for withdrawal, attempting to 
reschedule, etc. 
15.3 If a participant decides to withdraw, all data up to the point of their 
withdrawal will be kept. 
16.0 Risks to Subjects 
16.1 
 
• Drawing blood from the participant’s arm and hand include discomfort 
and/or bruising. There is a very low risk of infection, bleeding, clotting, or 
fainting.  
• Wearing activity monitors poses no known risks.  However, the participant 
may feel some discomfort while initially getting used to wearing the 
monitors.  In addition, a small percent of participants have developed a 
rash associated with the adhesive from the leg activity monitor. If any 
participant experiences any irritation, itching or redness while wearing 
either monitor, they will be instructed to stop wearing the monitor 
immediately and inform the study staff.   
• While the radiation used for the body scan (DXA scan) has no observable 
radiological or biological effect, there is always a risk associated with 
radiation exposure. 
• During the fitness test the participant will experience an increase in heart 
rate and blood pressure. Additionally, sweating will occur, and they may 
become fatigued, all of which are to be expected with exercise. It is also 
possible that abnormal responses may occur such as dizziness, unusually 
high increases in heart rate and blood pressure, and in rare instances, 
fainting. Trained personnel will be on hand during the fitness test. 
Emergency equipment is kept in the exercise testing room and all staff 
have been trained in its use. Following the fitness test, they may 
experience muscle soreness for a few days.  
• During the study the participant will be asked to eat three meals (breakfast 
and lunch during the appetite assessment, lunch following the clamp 
procedure). The study team will inquire about any food allergies the 
participant may have. 
• During and immediately after the clamp procedure there is a risk of 
hyperglycemia. We will monitor blood glucose every five minutes during 
the technique and for 1 hour following the technique.  
• There is also a slight risk of loss of confidentiality, meaning that someone 
could know the child participated in this study if they study team’s 

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research records are hacked. The participant’s confidentiality will be 
protected to the greatest extent possible.  
• Possible physical discomfort from the pressure from the NIRS 
muscle cuff 
16.2 Overall, the risks involved in this study are minimal. At this time we 
do not see any unforeseeable risks, but as information comes available 
we plan to report it to participants. 
16.3 We will screen for pregnancy prior to completing DXA scans on 
women of child bearing age (all women enrolling in the study), but 
there are risks associated with radiation exposure. 
16.4 Loss of confidentiality could affect parents/family of participants as 
well as participants. 
17.0 Potential Benefits to Subjects 
17.1 N/A – no benefit. 
17.2 Participants may experience no direct benefit. 
18.0 Investigator Assessment of Risk/Benefits Ratio: (IRB makes the 
final determination) Based upon your response in Sections 17.0 and 18.0, 
please provide your assessment of risk and benefits in below table. 
 
Select as applicable: 
Pediatric Risk Category: 
x 
Category 1  Research not involving greater than minimal risk  
(45 CFR §46.404 and 21 CFR §50.51)   
 
Category 2 
Research involving greater than minimal risk but 
presenting the prospect of direct benefit to the 
individual 
subjects. (45 CFR §46.405 and 21 CFR §50.52) 
 
Category 3 
Research involving greater than minimal risk and no 
prospect of direct benefit to individual subjects, but 
likely to yield generalizable knowledge about the 
subject's disorder or condition.  
(45 CFR §46.406 and 21 CFR §50.53) 
 
Category 4 
Research not otherwise approvable which presents 
an opportunity to understand, prevent, or alleviate a 
serious problem affecting the health or welfare of 
children. (45 CFR §46.407 and 21 CFR §50.54) 
Select if applicable: 
Adult Risk Category: 
x 
Not Greater than Minimal Risk 
 
Greater than Minimal Risk 
 
19.0 Data Management and Confidentiality 
19.1 Statistical Analysis Plan. To address Aim 1, we will compare 
groups (active vs. sedentary, normal weight vs. overweight/obese) 
using mixed models (linear or generalized, as appropriate) that adjust 

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for clustering of time points within person. For VAS appetite 
measures, which are assessed at multiple time points within a single 
measurement session, we will conduct analyses in two ways. First, 
we will conduct between group analyses using each of the seven 
individual assessments (e.g. 60 min post-meal) to see if the values 
differ by physical activity or body weight group. Second, we will 
also calculate area under the curve (AUC) for each variable of 
interest (e.g. hunger, ghrelin), and test for group differences on that 
measure using a linear or generalized regression model. To address 
Aim 1, hypothesis 2, we will repeat the analyses described above and 
include insulin sensitivity as a covariate.  
19.2 The sample size was determined by a review of similar studies 
indicating a range of 12-44 participants. 
19.3 All study staff will complete research training, save study documents 
on drives that require authorization of access, password protection, 
or encryption. Paper study documents will be protected using 
physical controls (such as being kept in secured locked offices in 
locked file cabinets). Study staff will keep identifiers separate from 
study IDs and data [master list]) during storage, use, and 
transmission.   
19.4 A Certificate of Confidentiality has been issued for this study.  
Certificates are automatically issued for NIH funded research per 
NIH policy.   
19.5 Study surveys will use a study ID for an identifier, study staff will 
lock documents in secure office locations and keep data collection 
surveys and instruments with them at all times when in use. 
19.6 Describe how data or specimens will be handled study-wide: 
• 
Study ID and visit date will be included on source 
documentation 
• 
Study documents will be stored in secure offices in secure file 
cabinets, Redcap, the W drive, or BOX (the study team has 
previous approval to use). 
• 
Study source documentation and other data will be kept at least 
3 years after submission of the Final Progress Report to the 
NIH. 
• 
The CMH study team, other approved staff members from 
approved organizations (KUMC, etc), the sponsor (NIH), the 
IRB. 
• 
The study lab coordinator, the PI. 
• 
No data will need to be transported, but blood samples will be 
transported to the analyzing lab through standard biohazard 

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shipping protocols. All data obtained off of CM premises will 
be accessed by study staff electronically via approved secure 
sharing platforms such as OneDrive.  
20.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
20.1 
Per NIH requirements: 
Plan for safety monitoring and review 
There will be a chair of the Data Safety Monitoring Board to make decisions 
on safety of the participants, as well as two other members members to 
serve in monitoring study progress and unanticipated/adverse events. Data 
will be reviewed twice a year by the Board Chair. If problems occur during 
the euglycemic clamp procedure, staff nurses will stop the procedure and 
notify the CTSU medical monitor, the Board Chair, and Dr. Shook of any 
issues. The Board Chair will then make a decision on whether the 
participant should continue with the remaining parts of the study. The PI and 
other key personnel will be examining research data on a subject to subject 
basis to ensure it is accurate and to address any potential problems that may 
arise with the protocols. In addition, Dr. Shook will examine data with KU 
team at least once per month through in person meetings or by phone to 
ensure that data collection is occurring in a consistent manner at both 
locations (KUMC and CMH). 
 
Plan for adverse event reporting 
Monitoring and reporting adverse events, whether anticipated or 
unanticipated, is the responsibility of the PI. The reporting requirements of 
the CMH and KUMC IRB’s and for serious and unexpected adverse events 
will be followed. All adverse events will be shared with Dr. Shook 
immediately and shared with the Board Chair and the DSMB within 48 hours 
of PI notification. 
 
Frequency of monitoring 
In addition to monitoring by the PIs, study coordinators, and safety officer, 
the IRB monitors all aspects of the project on an annual basis. The DSMB 
will review study progress (e.g., recruitment, retention, protocol adherence) 
and every six months at the semi-annual closed door session, per the DSMB 
charter. At the semi-annual DSMB session, the PI will provide a report 
detailing:  
a. List and summary of adverse events 
b. Whether adverse event rates are consistent with pre-study 
assumptions 
c. Summary of recruitment and retention and reason for dropouts 
d. Whether the study is on track to be completed and accomplish the 
stated aims. 
Section 4.1.6. ClinicalTrials.gov Requirements 

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In accordance with Public Law 110-85, this clinical trial will be registered in 
ClinicalTrials.gov.  
 
21.0 Provisions to Protect the Privacy Interests of Subjects 
21.1 Study participants will be given a study ID number and all the information 
they will out for the study will only have that ID number on it. The 
participant will only be linked to the study with their permission/assent form 
and a master linking list that connects their ID and name.  
21.2 Participants will be given ample time to think about participation including 
taking the permission/assent form home to think about it before signing up if 
they prefer. They will also be told about the study over the phone before 
coming in for the orientation visit. 
21.3 The study team will be given access to a linking list of participants so they 
may identify participants in this way to call and remind them of visits, etc. 
The study team will not leave detailed messages, will not post on social 
media, and will not share the name or any other PHI with anyone who is not 
a member of the study team. 
21.4 Identifiers recorded for this project: Name, Date of Service, Date of birth, 
medical record number, hospital account number, Street address, Telephone 
number, Email address, Social Security number (for payment purposes 
only). 
21.5 The research team will be obtaining HIPAA Authorization from 
subjects/parents to access and/or record PHI for this research study.   
• the HIPAA Authorization will be wrapped in with the 
permission/assent/consent form(s) 
22.0 Compensation for Research-Related Injury 
22.1 N/A – not more than minimal risk 
22.2 N/A – will use standard NIH contract language 
23.0 Economic Burden to Subjects 
23.1 N/A 
24.0 Permission/Assent/Consent Process 
24.1 Indicate whether you will you be obtaining 
permission/assent/consent, and if so describe: 
• 
P/A/C will be obtained electronically via eConsent over the 
phone or in person at the Don Chisholm building via eConsent.  
• 
Participants will be invited to ask questions and if they are 
uncomfortable enrolling at the time of the PAC conversation 
they will be told they can take the form home to think about it. 

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• 
As procedures are happening through the study they will be 
explained to the participant (and their parent/guardian). 
• 
We will be following CM research policies on informed 
permission/assent/consent.   
Subjects who are not yet adults (infants, children, teenagers) 
• 
Individuals <18 years 
• 
Parental permission will be obtained from a singular parent. 
• Permission may be obtained from individuals other than 
parents. These people will be determined to be Legally 
Authorized Representatives via court documentation either 
provided to the study team or already in the CMH HER.  
• 
Assent will be obtained from all children (our inclusion criteria 
includes only children of the age of assent). 
• 
When assent of children is obtained describe how it will be 
documented – children will sign and date the Permission 
Assent document. 
Consent at 18 years of age, when minor subjects become adults 
• We will re-consent any participants that turn 18 during the 
study with an adult addendum. 
Non-English Speaking Subjects 
• 
We plan to enroll only English speaking participants, due to the 
limitations of coordinating study visits with the assistance of an 
in-person interpreter.  
• We will utilize translation services or Cyracom to obtain 
permission/assent for any Spanish speaking parents of 
participants. We would request ORI to provide translations 
of our uploaded surveys and P/A forms. 
• 
 
25.0 Process to Document Permission/Assent/Consent 
25.1 
The study team will obtain permission/assent/consent via 
eConsent Lite over the phone or in-person at the Don 
Chisholm building at CM 
• The p/a/c process will take place via telephone or in-person at 
the Don Chisholm building on CM campus 

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• The potential participant will have a chance to ask questions 
and decide if they’d like to participate. 
• The only ongoing P/A/C process will include an adult 
addendum, if necessary for a participant that turns 18 during the 
duration of their study participation 
• The Study team will be following CM research policies on 
informed permission/assent/consent. 
• The study team may obtain permission/assent/consent via 
telephone, and will follow CM research policy (10.05 
Telephone Process). 
• The study staff listed on the IRB, as well as the study 
coordinator, and PI’s, may complete consent 
• Participants and their families will be given plenty of time to 
consider participation (they can decline to participate during the 
consent appointment and request follow up) as well as ask any 
questions they have. 
• Study staff will explain each main section of the p/a/c form as 
well as provide a summary. Checking for understanding while 
going through the form. 
• The study team will follow CM research policy for phone 
consent, if necessary (not in-person). This policy as well as 
other helpful guidance on the use of alternative communication 
methods to obtain permission/assent/consent are available in 
10.05 Telephone Process. 
Subjects who are not yet adults (infants, children, teenagers) 
• 
The study team will consider participants in the sample age 14 
- 17 not yet adults. 
• 
One parent will provide permission, even if the other parent is 
alive, known, competent, reasonably available, and shares legal 
responsibility for the care and custody of the child. 
• 
Permission may be obtained from individuals other than 
parents. These people will be determined to be Legally 
Authorized Representatives via court documentation either 
provided to the study team or already in the CMH records. 
 
26.0 Setting 
26.1 Describe the sites or locations where your research team will 
conduct the research. 

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• 
Participants will be identified and recruited from CMH, 
KUMC, and the community. 
• 
Research procedures will be performed at CMH and KUMC. 
• 
We will not be conducting research at any institutions outside 
the organization that have site-specific regulations or customs 
affecting the research or local scientific and ethical review 
structures outside the organization. 
27.0 Resources Available 
27.1 Describe the resources available to conduct the research: For 
example, as appropriate: 
• See the Power Analysis for more information about the sample size 
determination. All Study Personnel will complete research training 
required by their institution. 
• The following resources are available for the Energy Balance lab at 
Don Chisholm: DXA, laboratory equipped with freezer and hood, 
blood draw capabilities, exam rooms, fitness test equipment 
(treadmill, mask, monitors), thermic effect of feeding equipment. 
Study staff and graduate student support to complete the study 
measures as well as a kitchen on site to prepare the fixed/ad lib 
meals is also available.  
• There is an established partnership with KUMC and Dr. Shook. 
fMRI procedures are being utilized for another study that Dr. Shook 
is leading at the center currently. Dr. Shook is a volunteer faculty in 
the KUMC Department of Pediatrics. 
 
28.0 Multi-Site Research 
 
 
Choose ALL relationship types that apply:  
☐    Multi-Site Research: Multiple sites will be engaged in this human research 
project. Sites will use the same protocol to conduct the same human research 
activities (except for minor variations due to local context considerations).   
☒    Collaborative Research: Multiple sites will be engaged in this human 
research project. Sites will not be performing the same research activities. The 
Site submission will specify the specific research activities each site will perform.  
REQUIRED: Enter summary of site-specific activities that differ from the 
overall protocol: The insulin clamp procedures will be happening at the 

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KUMC CTSU. Also, we will have KUMC study personnel assisting with 
study procedures, data analysis, and manuscript preparation.    
☐    Student(s):  Student(s) will help with this project and will be engaging their 
home institution.  
☐    Visiting Resident(s) / Visiting Fellow(s):  Visiting Resident(s) / Visiting 
Fellow(s) will help with this project and will be engaging their home institution.  
 
Is Children’s Mercy (CM) acting as the single IRB of Record (sIRB)? 
☐    No, each site is getting their own IRB approval.  
☒    Yes, some or all sites will rely on the CM as the sIRB.  
• Reliance is required for non-Exempt NIH or other Federally 
Funded research where: 
o The institution's employees or agents intervene or 
interact with human subjects for research purposes;     
o The institution's employees or agents obtain 
individually identifiable private information or 
identifiable biospecimens about human subjects for 
research purposes; or     
o The institution receives a direct HHS award to conduct 
human subjects research, even where all activities 
involving human subjects are carried out by a 
subcontractor or collaborator.  
If CM is sIRB for another site, complete the chart for that site(s) (Add a new row 
for each site relying on the CM IRB, delete chart if not acting as sIRB): 
Site Name 
Enrollment Goal for 
Site(s) 
Choose One 
Relying on CM IRB?  
University of 
Kansas Medical 
Center 
☐  Site Enrollment 
Goal: Insert # 
 
☒  Site will not 
enroll  
☒  External Site will rely on the CM IRB as 
the IRB of Record using a reliance 
agreement. () 
☐  Not Applicable. Site will not interact or 
intervene with human participants or their 
identifiable data / identifiable biospecimens. 
Site is also not a primary NIH or federal 
grant recipient.   

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29.0 International Research 
29.1.  
N/A 
30.0 References 
 
1. 
Ogden, C.L., et al., Prevalence of obesity and trends in body mass index among US 
children and adolescents, 1999-2010. JAMA, 2012. 307(5): p. 483-90. 
2. 
Ogden, C.L., et al., Prevalence of childhood and adult obesity in the united states, 2011-
2012. JAMA, 2014. 311(8): p. 806-814. 
3. 
Barreira, T.V., et al., Normative steps/day and peak cadence values for united states 
children and adolescents: National Health and Nutrition Examination Survey 2005-2006. 
J Pediatr, 2015. 166(1): p. 139-43. 
4. 
Centers for Disease Control and Prevention, Youth Risk Behavior Surveillance. MMWR 
CDC Surveillance Summaries, 2014. 63. 
5. 
Shook, R.P., et al., Adherence With Multiple National Healthy Lifestyle 
Recommendations in a Large Pediatric Center Electronic Health Record and Reduced 
Risk of Obesity. Mayo Clin Proc, 2018. 
6. 
Foresight, Tackling obesities: future choices- Project report. 2007, Government Office for 
Science. p. 1-153. 
7. 
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