Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03158740 |
| Other study ID # |
123 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 7, 2017 |
| Est. completion date |
September 14, 2017 |
Study information
| Verified date |
October 2023 |
| Source |
Connecting Health Innovation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A large, persuasive, and ever-increasing body of evidence links chronic inflammation to
virtually all of the chronic diseases that cause the majority of disability and death in the
U.S., including diabetes, cardiovascular diseases (CVD), and cancer. Diet plays a central
role in the regulation of chronic inflammation. However, until investigators developed the
Dietary Inflammatory Index (DII)TM there had been no scientifically valid way to relate what
individuals eat to the capacity of foods consumed to modulate inflammation. The DII has now
produced an impressive research base that ranges from predicting blood levels of inflammatory
biomarkers; to a variety of health-related endpoints including cancer incidence and
mortality, diabetes, and CVD; to psychological endpoints including depression and cognitive
functioning. Watermelon is a member of the Cucurbitaceae family of gourds and is related to
the cucumber, squash, and pumpkin. Watermelon flesh (WM) is ~91% water by weight, and is a
rich source of bioavailable compounds including lycopene and other carotenoids, and vitamins
A and C, all of which have anti-inflammatory properties. Watermelon is already known to play
an effective role in reducing risk of chronic inflammation related conditions like coronary
heart disease. Connecting Health Innovations (CHI) through this proposal is committed to
developing a watermelon supplemented dietary intervention to reduce inflammation. The DII
provides a tool that will form the basis of a counseling/instructional system aimed at
helping patients and their providers to control chronic, systemic inflammation by improving
the diet with specific, actionable dietary recommendations, counseling, and expert
instruction. Our first aim is to refine and modify the DII-based intervention by developing
and incorporating several watermelon recipes which will score low (anti-inflammatory) on the
DII scale. Our second aim is to design and implement a two-arm intervention trial based on
watermelon-focused DII recommendations aimed at reducing levels of chronic inflammation in
Columbia, South Carolina; the two arms of this intervention study will be the DII-Based
Counseling System, including access to our Imagine Healthy Online Portal, and a general
health education control. Data will include questionnaires (e.g., demographics, health
history, stress, depression, self-efficacy for physical activity and diet, social approval,
social desirability), anthropometrics measures, physical activity monitoring, inflammatory
marker C-reactive protein (CRP), and ASA 24-hour dietary recalls. Baseline data collection
will be followed by a 12-week intervention period. The DII arm will receive in-person healthy
cooking and nutrition classes, along with physical activity and stress reduction activities.
Additionally, this arm will receive access to the Imagine Healthy Online Portal. The general
health control arm will receive weekly health education information. Linear mixed models
(LMM) will be used to determine whether the intervention arms are associated with the primary
outcome (i.e., CRP).
Description:
Study Objectives: Chronic inflammation underpins the development of numerous chronic diseases
that contribute significantly to disability and mortality in the United States (US). Of
particular interest, as it relates to inflammation, is diet which is a strong moderator of
systemic inflammation. Diets high in fruit and vegetable intake, fish, and whole grains
(e.g., Mediterranean and vegetarian diets) have been associated with lower levels of
inflammation. On the other hand, diets rich in red meat, high-fat dairy products, and refined
grains (Western diet) are typically associated with higher levels of inflammation. Up until
2014, no dietary index has been designed specifically to determine the inflammatory potential
of individual's diet. However, researchers in the Cancer Prevention and Control Program,
University of South Carolina developed the Dietary Inflammatory IndexTM (DII). The DII
quantifies the level of dietary inflammatory potential on a scale from maximally anti- to
pro-inflammatory. Watermelon is one of the fruits whose components have been shown to have
anti-inflammatory effects. The overall objective of this proposal is to determine if a
refined and modified watermelon-focused DII counselling system can reduce levels of chronic
inflammation. The DII is a validated measure that has been shown to predict a range of
outcomes including inflammation, cancer, CVD, and mortality, among others.
Specifically, the aims of this proposal are to:
1. Refine and modify the DII-based intervention by developing and incorporating numerous
watermelon recipes which will score low (anti-inflammatory) on the DII scale.
2. Design and implement a two-arm intervention trial based on the refined
watermelon-focused DII-based program for reducing levels of chronic inflammation. Each
arm will have 15 participants (plus an additional 15 partners recruited by the
intervention-arm participants). The intervention arm will receive the modified DII
intervention whereas the control arm will receive general health education.
Justification: Include summary of prior work and expertise related to the topic and
references cited: Until 2014 there had been no scientifically valid way to relate what
individuals ate to the capacity of foods consumed to modulate inflammation. In response to
the absence of an instrument that could summarize diets' ability to influence inflammatory
processes, investigators developed the DII which is based on literature (nearly 2,000
peer-reviewed journal articles) on diet and inflammation through 2010.20 The DII categorizes
individuals' diets according to their inflammatory potential. Additionally, it was found to
predict changes in hs-CRP in the Seasonal Variation in Blood Cholesterol (SEASONS) Study.
Subsequently, investigators have used the DII in about 100 datasets from around the world to
test the effect of diet-associated inflammation on: 1) Inflammation markers such as CRP,
IL-6, and TNF-alpha-R2; 2) CVD, 3) cancers of the breast, colon, prostate, ovary,
endometrium, liver and pancreas; 3) all-cause, CVD and cancer-specific mortality; 4)
respiratory conditions such as asthma; and 6) cognitive disorders. To date investigators have
published more than 80 peer-reviewed DII publications.
Study Design Overview: Investigators have extensive experience with diet interventions
spanning over two decades and involving a variety of endpoints including cancer, body weight,
and those related to CVD, inflammation, and immune response. Intervention venues have ranged
from the community (including worksites) and churches, research institute-based,to clinical
practice sites. This study will include two study arms (i.e., intervention and control).
Participants will be recruited from the community. Our goal is to recruit 15 participants per
arm, in addition to enrolling partners (e.g., spouse, child, sibling) of intervention
participants (n total = 45, n intervention = 30, n control = 15). Participants will undergo a
baseline clinic, followed by twelve weeks of intervention classes, and then another clinic.
The main intervention classes will take place at a state-of the-art demonstration kitchen
located in the Cancer Prevention and Control Program at the University of South Carolina's
Arnold School of Public Health.
Study Participants, Recruitment, and Randomization: Participants will be recruited from
greater Columbia, South Carolina via websites, fliers, newspaper ads, and listserv messages.
Eligible participants will: 1) be ≥18 years of age; 2) have no serious, unstable co-morbidity
that would make participation in a diet and PA intervention difficult or risky; 3) be willing
and able to participate fully in the study for a period of three months, 4) have Columbia, SC
area residence and be able to travel to and from the clinic and intervention sites; 5) have
access to the Internet; and 6) not be currently enrolled in a weight loss study or actively
taking weight loss medications. However, it should be noted that to see a reduction in
inflammation levels individuals need to have "room from improvement". Because it is costly to
screen all participants for inflammation (the primary outcome of this study) prior to
enrollment, a body mass index (BMI, kg/m2) of 25.0-49.9 will be used as an eligibility
criterion, as BMI is strongly associated with inflammation.
Anyone with one or more of the following criteria will be ineligible to participate in this
study: 1) taking any medications that are known to influence CRP levels such as systemic
steroids (e.g., prednisone); 2) diagnoses of congestive heart failure, chronic renal failure,
chronic liver disease (including alcoholic cirrhosis), cancer within the past year (except
for non-melanoma skin cancer); 3) have had any major surgery in the past 3 months; 4) life
expectancy <3 years, on hospice, nursing home or other institutionalized care; or 6)
currently pregnant or planning on becoming pregnant in the next year.
Recent attention to behavioral interventions has pointed out limitations in traditional
randomization schemes among these types of randomized controlled trials (e.g., inability to
truly blind participants, lack of decision making by participants). Other methods of
allocation, which take into account perceived ability to comply with intervention
requirements, are much more appropriate for this kind of intervention. Therefore,
investigators propose that only individuals who are motivated to make a healthy diet change
will receive the intervention.
Intervention Design: It should be noted that the cognitive and behavioral skills that will be
incorporated into the intervention are based largely on social cognitive theory and the
transtheoretical model. These include self-regulation (self-monitoring, setting goals,
problem solving, and reinforcement), enhancing behavioral competence, increasing
self-efficacy (through performance accomplishment, persuasion or encouragement, role
modeling, and making the experience pleasant), enhancing social support, stress management,
time management, relapse prevention, and incorporating changes into everyday life.
The two arms of this intervention study will be the DII-Based Counseling System, including
access to our Imagine Healthy Online Portal, and a general health education control.
Group-based behavior change programs provide a way for members to share successes and obtain
and provide support to one another. Both arms will be composed of 1 wave of 15 individuals.
Participants will be required to invite a partner of their choosing to join them in the
intervention activities to improve social support for behavioral change. Investigators have
experience conducting studies where participants invite partners to participate. Both arms
will undergo clinics for data collection at baseline and immediate post-intervention (i.e.,
at 12 weeks in both groups). Measurements include lipids (very low density lipoprotein
[VLDL], low density lipoprotein [LDL], high density lipoprotein [HDL], total cholesterol, and
triglycerides), insulin, and high-sensitivity c-reactive protein (hs-CRP). Anthropometric
measurements that will be obtained including height and weight (from which investigators can
compute BMI), and waist and hip circumferences.
The standard of care arm will receive general health information (e.g., general guidelines of
healthy eating and physical activity, stress management, cancer screening, etc.). This
information will be provided through email, which will include a weekly newsletter, healthy
recipes that are not focused on reducing the DII scores, links to online content, and
health-related event announcements in and around Columbia, SC. Any participants in the
standard of care arm who does not use email regularly may request for items to be mailed to
their mailing address.
The DII-based counseling group will utilize our 12-week IMAGINE Counseling System curriculum
that was developed as part of our previous SBIR award (R44DK103377).The DII-based counseling
group will meet once a week for 12 weeks to cook, and to engage in exercise and
stress-reduction activities. Along with the initial clinic, participants will meet one-on-one
for a nutrition counseling session with a registered dietitian. Participants will have access
to online material through our Imagine Healthy Online Portal and will be given take-home
activities, referred to as IMAGINE actions. These homework assignments will focus on goal
setting for nutrition, physical activity, and stress reduction. The nutrition components of
this intervention will be based on the DII and will focus on anti-inflammatory foods and
components. Some more specific aspects of the diet include increasing consumption of whole
foods (fruits and vegetables generally, legumes, and whole grain intake) and decreasing fat
(especially saturated and trans fats) that are known to influence inflammation. Examples of
strongly anti-inflammatory foods include dark green leafy vegetables, berries, spices and
herbs, and sweet potatoes, among others. Watermelon is an anti-inflammatory food (i.e., has a
low DII score) and will be incorporated into our nutrition component.
Weakly meal plans will be designed to provide participants with 2 meals per day that
incorporate watermelon. In each weekly class session, a recipe with watermelon as an
ingredient, will be demonstrated and prepared. These hands-on cooking demonstrations will
take place so that individuals learn how to prepare healthy, yet tasty, dishes. As is our
practice with our other dietary interventions, investigators will focus the experiential part
on sensations of taste and smell as well as tactile sensations, including things such as
cutting and washing vegetables. Investigators will rely on foods that are familiar to South
Carolinians and are available in local markets while exploring different methods of cooking
that incorporate spices from other parts of the world. Investigators have had extensive
experience with this type of design of dietary intervention. At the end of each session
participants will receive 1 whole Watermelon and 1-gallon bag of precut watermelon per week
during class. For continued reinforcement, participants in the DII-based counseling group
will have access to our Imagine Healthy Online Portal. The online portal will provide weekly
blog posts, a recipe database of 84 recipes that will incorporate watermelon into their meal
plans, interactive modules, and short vignettes of cooking tutorials. Information will
pertain to nutrition, physical activity, stress reduction, and making meaningful behavior
change. Some information will remain on the website from the beginning of the intervention
and additional information will be added weekly. Notifications will be sent out to
participants when new information is added. Additionally, intervention arm participants will
receive a weekly newsletter to their email.
The physical activity targets for this intervention will be consistent with physical activity
recommendations for adults. Participants will be encouraged to obtain at least 150 minutes of
moderate-intensity physical activity (equivalent to brisk walking) per week and to engage in
at least two sessions of strength training each week. To ensure safety, participants will be
encouraged to progress very gradually in increasing the intensity and duration of physical
activity from their baseline. For stress reduction, several techniques will be employed
including breathing exercises and mindfulness-based stress reduction (MBSR)-like activities.
Measurements: The primary exposure of interest will be the intervention arm status. However,
a focus of IMAGINE is to reduce sources of dietary inflammation. The DII is comprised of
various micro and macronutrients, as well as several individual food items, collectively
known as food parameters (more negative scores represent more anti-inflammatory diets and
more positive scores represent more pro-inflammatory diets). Participants will report their
diet using the Automated Self-administered 24-hour Dietary Recall (ASA24™).The ASA24TM was
created by the National Cancer Institute and includes a web-site for participant reporting
and a corresponding web-site for researchers to obtain the dietary information
(http://epi.grants.cancer.gov/asa24/). The DII will be calculated from ASA24TM data.
Previously, investigators have calculated the DII from this tool and found associations with
CRP.These self-assessments will take place at each data collection time point (i.e., baseline
and 12 weeks) where participants will report their dietary intake for two days on the weekend
and two during the week. The entire process of developing the DII is described elsewhere.9 In
short, nearly 2,000 research articles, published between 1950 and 2010, examining the
relationship between 45 different food parameters (mostly micro and macronutrients) and
inflammation were reviewed to derive inflammatory effect scores. Additionally, DII
calculation is linked to a regionally representative world database. The world database
contains standard means and deviations for the 45 food parameters from 11 populations around
the world.9 A z-score is created for each food parameter by subtracting the world standard
mean from the participants estimated intake, then dividing this by its standard deviation.
This is then converted to a percentile and centered by doubling the value and subtracting 1.
The product of the literature-derived inflammatory effect score and the centered percentile
for each food parameter is summed across all food parameters to create the overall DII score.
Higher (i.e., more positive) scores indicate more pro-inflammatory diets and negative values
are more anti-inflammatory.9 To control for the effect of total energy intake, the DII was
calculated per 1,000 calories of food consumed.
The primary outcome of interest will include the inflammatory marker hs-CRP. All blood
samples will be drawn from an antecubital vein or dorsal hand vein by a trained phlebotomist
while subjects are in the seated position. Blood will be collected using two serum separator
tubes (SSTs) at a capacity of 8 milliliters and one whole blood EDTA tube. The SSTs will be
processed and as many one milliliter aliquots (about 5) as possible of serum will be stored
for CRP, lipid, and insulin characterization. The whole blood will be for HbA1c%. All blood
samples will be collected in the morning after an overnight fast and information on fasting
and exact time of blood draw will be obtained. An acute-phase protein, CRP is a serological
marker of inflammation that is produced primarily by the liver in response to stimulation by
IL-6. CRP correlates with the magnitude and severity of inflammation. CRP has been associated
with the pathogenesis of several chronic diseases, including type 2 diabetes, cancer, and
CVD. It is one of the most commonly utilized markers of inflammation because of its chemical
stability, long half-life, and relative lack of diurnal variation.Total plasma concentrations
of inflammatory cytokines will be determined using quantitative sandwich ELISA kits provided
by R&D Systems, Inc. (Minneapolis, MN) for c-reactive protein (Catalog #DCRP00); sensitivity
= 0.022ng/mL. Samples and provided standards will be analyzed in duplicate, according to
manufacturer's instructions. Inter-assay and intra-assay variability will be assessed.
Secondary outcomes will include HbA1c%, insulin, and lipids. HbA1c will be measured in whole
blood collected in the EDTA tube using a Siemens/Bayer DCA 2000+ Analyzer and Test Kit DCA™
(SEMDIA-10311134), which efficiently performs hemoglobin A1c tests in minutes. Lipid analysis
will include very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density
lipoprotein (HDL), total cholesterol, and triglycerides using a standardized protocol.
Lastly, insulin concentrations will be determined using quantitative sandwich ELISA kits
provided by Mercodia, INC (Winston Salem, NC, Catalog #10-1113-01); sensitivity = 1.0 mU/L.
Actigraph GT3X-BT based PA and sleep: The GT3x-BT produced by Actigraph is lightweight (i.e.,
slightly less than 1 ounce) and is about the size of a wristwatch. Participants will be asked
to wear the GT3X-BT for 24 hours on their wrist, except during water-based activities, for 10
days around the clinic dates. Minimum wear time requirements will be 7 days (including
Saturday and Sunday) with at least 20 hours/day. During periods the GT3x-BT is not worn,
participants will report their activities in a log. Energy expenditure during non-wear time
will be estimated based on the Compendium of Physical Activities.168 The following PA
parameters are provided using propriety algorithms by the ActiLife 6 software for physical
activity: activity counts, energy expenditure, metabolic equivalents (METs), steps, physical
activity intensity, activity bouts, and sedentary bouts. The Actigraph GT3X products have
been validated in numerous studies. Sleep also will be characterized by the GT3X and has been
shown to be valid for sleep when worn on the wrist. Specifically, sleep duration, efficiency,
onset (i.e., bedtime), and offset (i.e., wake time) will be used.
Anthropometric measurements taken during each of the two clinic visits will include height
(cm), body weight (kg), and body fat percentage will be assessed according to standard
procedures using a wall-mounted stadiometer (Model S100, Ayerton Corp., Prior lake, MN) and
electronic scale (Healthometer® model 500 KL, McCook, IL) in bare feet. BMI (kg/m2) will be
calculated from measured weight and height. Waist circumference (cm) and hip circumference
(cm) will be measured with a calibrated, spring-loaded tape measure by trained technicians.
Blood pressure will be measured according to standard procedures using a stethoscope and
manual sphygmomanometer after the participant has been sitting for 5 minutes.
Covariates measured will include data on basic demographics, income, education, smoking,
other health behaviors and current medications. Investigators also will measure biases known
as social desirability and social approval using the 33-item Marlowe-Crowne Social
Desirability (MCSD) Scale and the 20-item Martin-Larson Approval Motivation (MLAM) scale.
Investigators will measure the effect of self-efficacy (confidence in the ability to change
across problem situations) beliefs about diet and PA using adaptations of previously
validated questionnaires. Depression and stress also will be measured using the Center for
Epidemiologic Studies Depression (scale) and the Perceived Stress Scale, respectively.
Statistical Analyses: All analyses will be performed using SAS® version 9.4 (Cary, NC).
Differences in descriptive covariates between study arms will be tested using chi-square
tests for categorical covariates and t-test (normally distributed) or Wilcoxon rank sums
tests (non-normal) for continuous measures. Investigators will employ linear mixed models
(LMM) to determine whether the intervention arms are associated with the primary outcome
(i.e., CRP). Specifically, outcome values (e.g., CRP) at time point 2 (i.e., 12 weeks) will
be modelled as the outcome. Intervention status, additional covariates, and the outcome
measure at baseline will be on the right side of the equation. Confounder selections will
begin with a series of multivariable analyses (i.e., time point two outcome = exposure +
covariate + baseline outcome). If a covariate has a p-value of ≤0.20, it will be added to a
full model. Confounders will include those that lead to a 10% change in the beta coefficient
of intervention status when the confounder is removed; significant covariates (p≤0.05) also
will be included in final models. The residuals for all final models will be examined for
their adherence to the assumptions of linear regression. If the assumptions are not met,
other analytical approaches can be taken. For example, quantile regression is an analytic
technique that allows for an assessment of associations throughout the distribution of the
outcome of interest.Additionally, CRP has a standard cut-point of 3.0mg/L for clinical
reference. Therefore logistic regression can be used to obtain odds ratios [OR] and 95%CIs
for the different intervention arms based on this cut-point.
