Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05443347 |
| Other study ID # |
STUDY00002194 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 14, 2022 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Children's Mercy Hospital Kansas City |
| Contact |
Robin P Shook |
| Phone |
2144488366 |
| Email |
rpshook[@]cmh.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of the study is to quantify the relationship between physical activity,
metabolic function, and appetite in adolescents. To do this we will test our working
hypothesis that high levels of regular moderate-to-vigorous physical activity (MVPA), as
opposed to body weight status, results in a metabolic phenotype consisting of enhanced
metabolic function and proper regulation of appetite. We will randomly assigning sedentary
overweight/obese adolescents (N=44) to either a control or structured-exercise group for
three months.
Description:
he objective of the study is to quantify the relationship between physical activity,
metabolic function, and appetite in adolescents. To do this we will test our working
hypothesis that high levels of regular moderate-to-vigorous physical activity (MVPA), as
opposed to body weight status, results in a metabolic phenotype consisting of enhanced
metabolic function and proper regulation of appetite. We will randomly assigning sedentary
overweight/obese adolescents (N=44) to either a control or structured-exercise group for
three months.
Our study statistician Dr. Vincent Staggs will randomize participants after final eligibility
is determined to either the newsletter control or exercise intervention, balanced by gender
to ensure equal composition of males and females.
The sample size for Study 2 (Aim 2) was calculated based on data from our lab; a small pilot
study with sedentary and active periods to test the feasibility of our laboratory protocols.
Based on this preliminary data, which is similar to data in the existing literature, we
estimate changes in appetite ratings (hunger) 11% from baseline, equating to effect sizes of
0.67, resulting in sample size calculations of N=35. Assuming a drop-out rate of 10% (n=4)
during the three month intervention, which is typically observed in similar interventions
conducted by Mentor Dr. Donnelly, final sample size is set at N=40.
Data analysis will be completed by the PI with assistance from the statistician Dr. Staggs
and the mentorship team. For visual analog scale (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 use that measure for the test of group differences. To
address Aim 1, hypothesis 2, we will repeat the analyses described above and include insulin
sensitivity as a covariate. To address Aim 2, hypothesis 3, we will conduct between group
analyses of change over time using repeated measures ANOVA, using the same analysis
techniques for the appetite variables as described in Aim 1 (single assessment and AUC), with
insulin sensitivity included as a covariate.
Appetite is considered the primary outcome of Aim 1 and 2. Subjective assessment of hunger
and palatability will be completed using self-rated visual analogue scales (VAS), with each
scale consisting of a 10-cm long line separating statements such as ?not at all hungry? and
?extremely hungry?. Perceptions of dietary restraint, disinhibition, and hunger will be
measured during each measurement session prior to the fixed meal using the Three Factor
Eating Questionnaire (TFEQ). 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. 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 ?L of
10,000 KIU aprotinin), centrifuged, the plasma divided into aliquots and stored in -80?C
freezer until analysis using standard kits at an outside certified clinical laboratory.
Appetite measured will be assessed following a fixed standard breakfast (40% of RMR, composed
of 55% carbohydrate, 15% protein, 30% fat). The fixed breakfast will be administered while
the participant is in a fasted state (?12 hours since last meal) and they will be asked to
consume the meal within 15 minutes. Food intake (total kcals) will be assessed using an ad
libitum pizza 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. Meals will be provided in 400 kcal portions, and each bowl of food will be weighed
before and after serving, without the subjects? knowledge, and the amount consumed recorded.
All meals will be served in a quiet dining room free from distractions located at CCHLN. All
foods will be prepared using a standard procedure in the metabolic kitchen to ensure
consistency across the treatment conditions, and nutrient composition of the meals will be
determined using nutrient analysis software (Nutrient Data System for Research, version
2016).
Insulin sensitivity via the euglycemic ?hyperinsulinemic clamp technique is considered the
primary outcome for Aim 1, hypothesis 2. Participants will arrive fasted (12-hours
overnight). A catheter will be inserted into an antecubital vein of one arm to infuse insulin
and 20% dextrose, and another catheter will be inserted into the contralateral antecubital
vein for blood sampling. The participant will rest quietly and RQ via indirect calorimetry
will be measured (see Resting Metabolic Rate), followed by collection of 3 baseline blood
samples to establish baseline glucose levels. Immediately following and lasting for 180
minutes, a primed continuous infusion of regular human insulin will be administered at a rate
of 40 mU?m2 body surface area?1?min?1 along with a variable infusion of 20% dextrose to
maintain euglycemia to match baseline levels (expected 90-100 mg/dL). Blood glucose
measurements will be completed every five minutes for determination of glucose infusion rate
using a YSI-2300 analyzer. Furthermore, every ten minutes blood will be drawn into serum
separator tubes, centrifuged, and stored at -80? C for later insulin analysis. RQ will again
be measured 2 hours into the clamp for a period of 15 minutes. Insulin sensitivity will be
determined by the glucose disposal rate during the final 45 min of the
hyperinsulinemic-euglycemic clamp when euglycemia has been established. This procedure will
occur at the KUMC Clinical and Translation Science Unit research facility.
Adolescents will be randomly assigned to either an exercise or newsletter control condition
for three months. Adolescents randomized to the exercise will participate in a supervised
structured exercise program (walking on a treadmill, cycling on a stationary bicycle, etc.)
and expend an equivalent of 400 kcals/session (approximately 45-60 min/session) on three
days/week. We will follow the protocol of Mentor Dr. Joseph Donnelly, with exercise
prescriptions progressing from 150 kcal/session at intervention onset to reach the target
exercise energy expenditure (EEEx) (400 kcal/session) at the end of month 3. The rationale
for this dose of structured exercise is based on national and international physical activity
recommendations for youth of 60 minutes/day, along with data from the Donnelly team and
others that indicates this level of exercise over a three month period will result in
improvements in cardiorespiratory fitness in adolescent participants.
EEEx will be assessed at baseline and monthly during the intervention to determine the
duration of treadmill exercise required to achieve the EEEx goals. EEEx will be assessed by
indirect calorimetry (TrueOne 2400 Metabolic Measurement Cart, ParvoMedics, Salt Lake City,
Utah) at one minute intervals. The Weir equation will be used to calculate EEEx from measured
oxygen consumption and carbon dioxide production. Prior to each EEEx assessment participants
will perform a brief warm-up (~ 2 minute, 3?4 mph, 0% grade). At the baseline assessment,
treadmill speed/grade will begin at 3 mph/0% grade and will be adjusted by increments of 0.5
mph/1% grade until the participant reaches 70% HR max ?4 beats/minute. At the end of months 1
to 3, EEEx will be calculated at both 70% and 80% of heart rate (HR) maximum to accommodate
personal preferences for walking or running. EEEx will be assessed at both 70% (15 minutes)
and 80% HR max (15 minutes) with a 2 minute interval between assessments to allow
participants to remove the mouthpiece and obtain water if desired. Either speed or grade will
be adjusted depending on participant preference. The average EEEx over a 15 minute interval
(kcal/minute) will be used determine the duration of exercise sessions performed during the
first month. For example: EEEx = 9.2 kcal/minute, prescribed exercise = 400 kcal/session,
exercise duration = 400/9.2 = 44 minutes/session.
All supervised exercise will occur at the CCHLN on a treadmill with heart rate, speed, and
grade monitored by an exercise specialist every five minutes. Televisions and iPads will be
available for the participants to watch while exercising. Compliance will be defined as
completion of ?90% of scheduled exercise sessions/week and participants will be excluded if
they fail to meet this requirement. Successful completion of an exercise session will be
defined as maintaining target HR ?4 beats/minute for the prescribed exercise duration.
As has been done in previous studies by pediatric obesity treatment experts we will use a
newsletter control group. Just as in these previous studies, families will receive a monthly
newsletter with ?parenting tips, sample praise statements, and child-appropriate activities
and recipes? identical to what has been used in the work of leaders in the field of pediatric
obesity. The content will be similar to that delivered in existing group based interventions
with overweight/obese adolescents at the CCHLN under the direction of Mentor Dr. Ann Davis.
Energy intake will be assessed using three methods: 1) objectively, as measured by amount of
kcals consumed during an ad libitum meal (see above, section Fixed/Ad libitum meals), 2)
subjectively, assessed in each free-living 7-day assessment period via dietician-administered
24-hour dietary recalls, and 3) calculated, based on intake-balance method. Subjective energy
intake will be assessed using three dietary recalls occurring on randomly selected
non-consecutive days over each 7-day free-living assessment period (including at least one
weekend day) to minimize preparation that could bias recall, by a team of experienced (>6
years using Nutrient Data System for Research software) registered dietitians employing a
multi-pass approach, which utilizes prompting to reduce food omissions and standardizes the
interview methodology across interviewers. Estimated energy intake will also be calculated
using the intake-balance method during each treatment condition, based on the principles of
the First Law of Thermodynamics, using the following equation: calculated energy intake=
1,020 (?FFM/?t) + 9,500(?FM/?t) + EE, where ?FFM and ?FM represent change in each variable as
measured by DXA at the beginning and end of each assessment period condition, ?t represents
days between measurements; 1,020 and 9,500 represent the energy density in kcals of FFM and
FM per kg, respectively; and EE represents energy expenditure as measured by the activity
monitor.
Energy expenditure will be estimated during each 7-day free-living assessment period using an
arm-based monitor (SenseWear Mini?, BodyMedia Inc.), which calculates energy expenditure
using tri-axial accelerometry and measures of heat flux, galvanic skin response, skin
temperature, and near-body ambient temperature.
Body composition including fat mass and fat-free mass will be measured using a whole-body
dual energy X-ray absorptiometer (DXA, Lunar DPX system, version 3.6) with the participant
dressed in surgical scrubs and in bare feet.
