Feasibility and Acceptability of a Beverage Intervention for Hispanic Adults
Phase: NA
Conditions: Obesity, Hypercholesterolemia, Hyperglycemia, Hypertriglyceridemia
Sponsor: University of Arizona

Feasibility and Acceptability of a Beverage Intervention for Hispanic Adults 
NCT02911753 (ClinicalTrials.gov) 
Registered September 19, 2016. Last updated November 1, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Aims and Study Hypotheses 
This pilot study will expand on earlier research by our team using beverage interventions to 
enhance cardiometabolic health. This study’s primary objective is to assess the feasibility and 
acceptability of a beverage intervention in obese Hispanic adults. Primary feasibility outcomes 
will be recruitment, retention, and acceptability. Beverage intake will also be assessed through 
intake diaries and beverage return rates during weekly clinic visits. The preliminary efficacy of 
the beverage intervention will assess changes in total cholesterol, high-density lipoprotein 
(HDL), and low-density lipoprotein (LDL) over 6-weeks. Secondary outcomes are changes in 
fasting glucose, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP). 
Our study will evaluate participant-reported tolerance and as an exploratory aim, our study will 
also assess safety/toxicity-related to renal and/or liver function as albeit limited, evidence from 
green tea polyphenol E supplementation studies have reported a few cases of hepatic toxicity 
with on-going supplementation [1]. Renal and hepatic toxicity function will be assessed at 
baseline and 6-weeks. The aforementioned outcomes will be examined to test the following 
hypotheses: a) recruitment and retention of obese Hispanic participants in a 6-week beverage 
intervention study is feasible; b) the consumption of green tea and Mediterranean lemonade will 
be well-tolerated with high adherence; and c) green tea and Mediterranean lemonade intake will 
result in an improved cardiometabolic profile at the end of 6-weeks.  
 
 
 
 

Design and Methodology 
Design 
This study is a pilot randomized controlled trial where participants are randomized to one of 
three beverages: Green Tea (GT), Mediterranean lemonade (ML), or a Flavored Water control 
(FW). Participants will be stratified by gender using block randomization and an allocation ratio 
of 2:2:1 with variable block sizes. A computer randomization system will be used to complete 
the randomization assignment. We propose to consent 150 individuals to randomize 50 
participants into our 6-week study. Following consent and baseline assessments, randomization 
assignment will be determined and documented in the participants’ study record and shared with 
the participant. Assessments will be performed by blinded study personnel. Under no 
circumstances will unblinding be permissible. Investigators, intervention staff, and participants 
will not be blinded for the study. The schedule of the enrollment, interventions, and assessments 
according to SPIRIT requirements is shown in Figure 1. 
 
 
 
 
 
 
 
 
 
 
 

Figure 1. Content for the schedule of enrollment, interventions, and assessments according 
to SPIRIT requirements 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PERIOD 
 
Enrollm
ent 
Allocation 
Post-
allocation 
Close-
out 
TIMEPOINT** 
-t1 
0 
t1 
tx 
ENROLLMENT: 
 
 
 
 
Eligibility screen 
X 
 
 
 
Informed consent  
X 
 
 
 
2-Week Run-In 
X 
 
 
 
Allocation 
 
X 
 
 
INTERVENTIONS 
 
 
 
 
Green Tea 
 
 
 
 
Mediterranean 
Lemonade 
 
 
 
 
Flavored Water 
Control 
 
 
 
 
ASSESSMENTS: 
 
 
 
 
      Anthropometry  
 
 
X 
X 
Cardiometabolic 
Measures 
 
 
X 
X 
Self-Reported 
Questionnaires  
 
 
X 
X 

Setting of the Human Research  
Research activities will take place at the University of Arizona Collaboratory for Metabolic 
Disease Prevention and Treatment in Tucson, AZ. All procedures have been approved by the 
University of Arizona Institutional Review Board.  
 
Study Population 
We will recruit 50 obese Hispanic adults aged 18-64 years living in the Tucson area. Individuals 
will be considered eligible if they met all of the following criteria: self-identified as Hispanic, 
18-64 years of age, BMI between 30-50.0 kg/m², able to provide informed consent, and able to 
speak, read, and write in either English and/or Spanish. Individuals were excluded if they met 
any of the following criteria: diagnosis of diabetes mellitus; history of liver disease; current 
medication for glucose control; cholesterol control; uncontrolled blood pressure; current eating 
disorders such as anorexia nervosa; bulimia, etc. (likely to make adherence to prescribed 
beverage intake difficult); current alcohol or substance abuse; currently treated for psychological 
issues (i.e. depression, bipolar disorder, etc.); taking psychotropic medications within the 
previous 12 months or hospitalized for depression within the previous 5 years; report exercise on 
≥3 days per week for ≥ 20 minutes per day over the past 3 months; reported weight loss of ≥5% 
or participating in a weight reduction diet program in the past 3 months; reported plans to 
relocate to a location that limits their access to the study site or having employment, personal, or 
travel commitments that prohibit attendance to all of the scheduled assessments; reported plans 
to relocate to a location that limits their access to the study site or having employment, personal, 
or travel commitments that prohibit attendance to all of the scheduled assessments; or reported 

consumption of ≥ 1 cup of green tea and/or citrus fruit daily and were not willing to complete 2-
week run-in period.  
 
Study Recruitment 
Recruitment efforts will primarily target local community-based settings such as clinics, health 
fairs, and outdoor marketplaces frequented by Hispanic communities in Tucson, AZ. Additional 
recruitment strategies included the use of social media posts (e.g., Facebook, and Craigslist) and 
health provider initiated approaches (e.g., patient referral). Participants of preliminary studies 
who had expressed interest in health behavior research and had signed consent to be contacted 
for future intervention studies also were contacted. Potential participants were instructed to call 
study staff and a telephone screening was conducted to determine initial eligibility. Interested 
individuals engaged at recruitment settings were given the option of being screened on-site or 
during a future phone call with study staff. Telephone and on-site screenings included a detailed 
description of the study and its potential risks and benefits. Upon the participants’ verbal 
agreement, study staff asked questions regarding medical history and other pertinent questions 
related to exclusion/inclusion criteria.  
 
Informed Consent 
All eligible participants will be invited to the Collaboratory where complete details of the study 
will be provided in the participants’ preferred language (Spanish or English). During this time, 
participants will be encouraged to ask questions about the study’s procedures. Interested 

participants will provide written informed consent to study personnel using consent forms that 
are available in the participants’ preferred language. 
 
Certificate of Confidentiality  
To help us protect the participant’s privacy, we obtained a Certificate of Confidentiality (CC-
DK-17-003) from the National Institutes of Health, National Institute of Diabetes and Digestive 
and Kidney Diseases (NIDDK). This Certificate can be used legally to refuse to disclose 
information that may identify participants in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings, for example, if there is a court subpoena. 
 
Study Intervention 
Study personnel will prepare all study beverages. Lipton® Decaffeinated Green tea will be 
prepared using a ratio of 4 tea bags per 32 oz. water. Upon reaching a boil, tea bags will be 
steeped into water for 3-5 minutes. When slightly cooled, 4 drops of Liquid No Calorie Stevia™ 
will be added per 32 oz. of tea. To prepare the Mediterranean lemonade, two full lemons will be 
de-seeded and blended with 32 oz. of water and 4 drops of Liquid No Calorie Stevia™.  The 
control beverage will be prepared using 4 drops of Crystal Light Liquid Drink Mix (strawberry 
lemonade) per 32 oz. of water. All beverages will be prepared two days prior to participant pick-
ups. All green tea will be kept frozen while the Mediterranean lemonade and flavored water will 
be refrigerated for storage and distribution to study participants. Preparation and storage 
procedures were informed by prior chemical analysis of bioactive components in the beverages 
across seven days to assure optimal exposure. Mean epigallocatechin gallate (EGCG), the main 

polyphenol found in green tea, was 161.5 mg per 32 oz. and mean d-limonene was 373.4 μg/ml 
per 32 oz. in the Mediterranean lemonade. All analyses were conducted by the UA Cancer 
Center Analytical Chemistry Shared Resource. 
 
Participants will complete a 2-week run-in period prior to beginning the 6-week intervention. 
During this period, participants will be asked to stop all tea and citrus fruit consumption and 
limit consumption of any beverages except water. Each participant will be provided with a 32-
ounce Hydro Flask® to support regular intake of the prescribed beverage. This run-in period will 
determine the feasibility of consuming 32 oz. each day for participant adherence to the beverage 
intervention.  
 
Upon successful completion of baseline assessments and 2-week run-in, participants will be 
randomized to a beverage assignment. All participants will be advised to consume the entire 
beverage assigned on a daily basis (rather than save up and consume large amounts on fewer 
days). At the start of the intervention, participants will be asked to continue avoiding all other 
sources of tea, lemonade, and citrus, limit coffee consumption to 2 cups/day, avoid all sweetened 
beverages other than study-provided drinks, consume water ad lib, and avoid alcohol in excess of 
1 drink/day for women and 2 drinks/day for men. In addition, participants will be asked to self-
monitor their beverage consumption behaviors using a weekly journal to help habitually regulate 
beverage intake. Participants will be responsible for picking up one week’s worth of beverages 
once per week from the study clinic. Participants will be asked to return any un-consumed 
beverages during weekly pick-ups; study staff will measure and record any amount not 

consumed. Weekly beverage journals will also be collected and new ones distributed for use the 
following week. Brief in-person interviews or “check-ins” lasting 5-10 minutes will also take 
place during this time with bilingual study staff. These interviews will follow a script to review 
beverage-related behaviors and identify and address specific barriers for adherence to study 
beverage intake.  
 
Retention Strategies  
We will use common strategies to enhance participant retention, including: 1) collecting contact 
information of participants and at least two family members; 2) program reminders; 3) incentives 
to complete assessments; and 4) contacting participants at their preferred time by their preferred 
method (i.e. call or text) in their preferred language.  
 
Participant-Reported Tolerance or Toxicities 
Potential risks may include but are not limited to: nausea, vomiting, frequent bowel movements, 
flatulence (gas), acid reflux, excess burping, heartburn, and bloating. If a participant experiences 
any of these signs/symptoms associated with beverage intake, they will be given the option to 
withdraw from the study or change to the alternate beverage intervention (but not flavored water) 
after a 1-week washout period.  Participants will be asked on a weekly basis about any issues 
related to their beverage consumption and this information will be noted. Prior literature has 
reported a few cases of hepatic toxicity related to supplementation with high-dose green tea 
polyphenols [1]. No evidence exists to suggest toxicity or safety issues related to the green tea 
nor Mediterranean lemonade beverages consumed in the amounts prescribed for this study. 

Therefore, renal and hepatic function will be monitored at study beginning and end using alanine 
transaminase (ALT) or aspartate transaminase (AST) values. Abnormal values will be shared 
with the participant and the participant will be advised to visit their physician for evaluation. In 
the event this occurs, participants will not receive additional compensation and the study will not 
cover additional costs for physician follow-up. 
 
Methods for Assessing Study Outcomes and Potential Confounders 
Anthropometry 
Height, body weight, waist circumference, and resting blood pressure will be measured at 
baseline and 6-weeks. Height will be measured to the nearest 0.01 centimeter (cm) using a 
ShorrBoard® wall-mounted stadiometer with participants removing their shoes prior to the 
measurement.  Two measurements will be taken.  A third measurement will be taken if the first 
two measurements differ by more than 0.5 cm.  The average of the two measurements which met 
the criteria above will be recorded for data collection. Body weight will be measured using a 
Seca 876 scale to the nearest 0.1 kilogram (kg) on a digital scale without shoes. Two 
measurements will be taken. A third measurement will be taken if the first two measurements 
differ by more than 0.2 kg. The average of the two measurements which meets the criteria above 
will be recorded for data collection. BMI will be calculated using body weight in kilograms 
divided by squared height in meters (kg/m²). Waist circumference will be obtained using a 
Gulick measuring tape recorded to the nearest 0.1 cm. Waist circumference will be measured in 
the horizontal plane directly at the umbilicus. Two measurements will be taken at each site. A 
third measurement will be taken if the first two measurements differ by more than 2.0 cm. The 
average of the two measurements closest to each other will be recorded for data collection.  

Resting blood pressure and heart rate will be measured using the Omron Digital Blood Pressure 
Monitor HEM-907XL on the participant’s left arm. Using a Gulick measuring tape, an arm 
measurement will be performed on the lateral aspect of the left arm at the midpoint between the 
acromion process to the olecranon process to determine the appropriate cuff size. Upon a five-
minute resting period with the participant in an upright position with feet flat on the floor, two 
blood pressure measurements will be taken with a one-minute time period between each 
measurement. A third blood pressure will be taken if the mean difference between the systolic 
blood pressure measurements differs by 10 mmHg or greater and/or the diastolic blood pressure 
measurements differs by 6 mmHg or greater. The average of the two measurements which meets 
the criteria above will be recorded for data collection. In addition, if the mean resting systolic 
blood pressure is ≥150 mmHg or average diastolic blood pressure is ≥100 mmHg at baseline, the 
participant will be excluded from participation and referred back to their physician. 
 
Biological Samples 
Emerging evidence indicates that genetic variation may impact the efficacy of lifestyle 
behavioral interventions [2]. Therefore, we will perform a buccal cell collection by using a 
cytology brush to brush the inside of each check for 30 seconds for the extraction of DNA and 
subsequent genetic analyses. This optional non-invasive, self-collection of buccal cells will occur 
at one time and will be performed at either the baseline (preferable) or follow-up visit. 
Participants also will have the option of allowing the study investigators to store some of the 
blood that was taken but not used for other tests. This will allow the researchers to derive 
metabolomics and molecular data that are complementary in obesity research and provide value 
for enhancing precision care in this health disparate population. 

Cardiometabolic Measures 
Fasting blood samples (venipuncture; 25 mL), will be collected at baseline and 6-weeks, by a 
trained phlebotomist, for the purpose of examining the following cardiometabolic measures: total 
cholesterol, triglycerides, HDL, LDL, very low-density lipoprotein (VLDL), HbA1C, hs-CRP, 
and fasting glucose. A comprehensive metabolic liver/kidney panel will be performed to assess 
the following: albumin, globulin, A/G ratio, total protein, alkaline phosphatase, ALT, AST, total 
bilirubin, blood urea nitrogen (BUN), calcium, creatinine, BUN/creatinine ratio, glomerular 
filtration rate/estimated, and electrolytes (sodium, potassium, chloride, carbon dioxide). All 
laboratory tests will be performed by an independent, clinical lab (Banner University Medical 
Center, Tucson, AZ), blinded to the study outcomes. 
 
Physical Activity 
Physical activity will be assessed at baseline and 6-weeks using the Global PA Questionnaire 
(GPAQ) [3, 4]. It is available in both English and Spanish and provides minutes/week of 
physical activity of varying intensity and type. The GPAQ has been validated compared to 
accelerometer data in determining time spent in moderate-to-vigorous physical activity (MVPA) 
and to assess changes in physical activity over time. Cleland et al. [4] found a moderate 
agreement between the GPAQ and accelerometer for MVPA mins/day (r = 0.48) and results for 
agreement in changer over time showed moderate correlation (r = 0.52, p = 0.12). Similar 
correlations have been reported for the GPAQ compared to accelerometer data for Hispanic 
women participating in a 6-month physical activity intervention [3].  
 
 

Diet  
Diet assessment will be completed at baseline and 6-weeks using the Southwestern Food 
Frequency Questionnaire (SWFFQ) [5-7], a bilingual FFQ that includes food items commonly 
consumed by Mexican Americans and uses Mexican names for food items commonly given 
different names by other Spanish speakers (e.g., “naranja”, not “china”, for “orange”). Output 
data from the SWFFQ will allow us to calculate daily intake of total sugar, saturated fat, sodium, 
fiber, whole grains, and fruits/vegetables. Internal validity of the SWFFQ compares favorably 
with 24-hour recall (r=0.82) [5]. SWFFQ data will be analyzed using the 2009 United States 
Department of Agriculture (USDA) Nutrient Data Bank.  
 
Tea Consumption 
We will assess tea consumption at baseline and 6-weeks using the Arizona Tea Questionnaire. 
This 28-item scannable questionnaire has been tested for short and long-term reliability as well 
as relative validity [8]. This questionnaire asks about usual tea intake over the past year, as well 
as lifetime consumption patterns including amount, type, and preparation technique. The output 
is provided in total flavonoids, total polyphenols, catechins, theaflavins, thearubigins, caffeine, 
and gallic acid.  
 
Psychosocial Measures and Acculturation 
We will use the following self-reported questionnaires to assess psychosocial measures at 
baseline and 6-weeks which may influence diet and physical activity behaviors: Self-efficacy [9] 
and social support for diet [10], The Acculturation Rating Scale for Mexican Americans–II 
(ARSMA-II) [11] will be used to measure acculturation related to language, ethnic identity, and 

ethnic interaction. The reliability, and validity of the ARSMA-II are well established in English 
and Spanish [11].  
 
Statistical Analysis Plan 
Feasibility outcomes 
The primary feasibility outcomes are recruitment and retention. We aimed to recruit, on average, 
approximately 2-3 participants per week during the active recruitment phase. A recruitment rate 
of less than this would indicate a lack of feasibility. We recorded the number of Hispanic adults 
who contacted the researchers and expressed interest in participation, the number screened for 
eligibility, and the number ineligible for study inclusion and the reason for their ineligibility. 
Retention will be assessed by calculating the proportion of participants who completed the study 
out of the number enrolled, with a 95% confidence interval.  
 
Treatment Satisfaction/Acceptability 
At the completion of the study, participants will take part in an exit interview where they will be 
asked to rate their overall satisfaction with the intervention, if they would consider a longer-term 
beverage intervention, and finally, if they would recommend the program to others. Participants 
will also be asked questions regarding satisfaction with their overall progress and for changing 
dietary beverage habits. Each item will be rated on a Likert scale with higher scores indicating 
greater program favorability. Open-ended questions will be used to seek participant input on 
modifications that could be made to improve acceptability and effectiveness of the intervention. 

The responses will be used to identify which recruitment and intervention components were well 
received, which could be improved, and which were not acceptable. 
 
Efficacy Outcomes 
Descriptive statistics, including means, ranges, and standard deviations, will be calculated for the 
primary efficacy outcomes, cholesterol/lipid levels, and the secondary outcomes: fasting glucose, 
HbA1c, and hs-CRP. Mixed models will be used to compare arms in each of these outcomes’ 
change from baseline. We will include fixed effects of intervention arm, time and their 
interaction to allow for different patterns of change between the arms, as well as a random 
participant effect to account for the longitudinal nature of the data. Baseline values of the 
outcomes will be included in the dependent variable vector. The changes from baseline, and the 
differences between arms in change from baseline will be estimated using contrasts from the 
mixed models. Mixed models yield unbiased estimates for data that are missing completely at 
random (when missingness does not depend on any observed or unobserved data) and missing at 
random (when missingness may depend on observed data, such as the baseline value of the 
outcomes), as these models perform an implicit imputation [12, 13]. Data from all patients who 
are randomized will be analyzed in the arm that they were randomized to.  
Sample Size Calculation  
The total sample size of 50 will provide 95% confidence intervals for the primary feasibility 
outcomes (proportion of eligible participants who enroll and the proportion of participants 
retained in the study) that are no wider than 0.28 (±margin of error = 0.14), conservatively 
assuming a base proportion of 0.5, which maximizes the standard error. The trial will be 

considered feasible if the proportion retained is greater than 70%. If retention in the study is 81% 
or greater, the 95% confidence interval will not contain this 70% cutoff. Power will be 
insufficient to detect a minimum important difference of a 6 mg/dL change in fasting lipids from 
baseline, the primary efficacy outcome, based on variance estimates from a trial using a different 
fruit [14] (standard deviation ≈25mg/dL). We acknowledge that we are not sufficiently powered 
to detect important differences between arms, but if the 95% confidence intervals for the 
comparison of the arms contain important differences we will take this as indication of a 
promising intervention. Variance components estimated from this study will be used to design an 
adequately powered trial. 
 
Data Management 
 Data management will be conducted according to Good Clinical Practice guidelines to enhance 
data quality assurance and control. This will include standard operating procedures and staff 
trainings for data acquisition, entry, and processing. Further, information obtained from this 
research will be kept confidential to respect the participant’s privacy. All records will be stored 
and locked in a file cabinet. In addition, all research databases will have password-controlled 
access, and the researchers will control this access.  Data analyses will take place using a 
dedicated study computer upon study completion. No interim analyses will be performed. Study 
data will be uniquely coded for each subject and then entered via secure server to a Research 
Electronic Data Capture (REDCap) database maintained by the Clinical and Translational 
Sciences Research Center (CATS) at the University of Arizona. Only local study personnel will 
have access to identified study data. Once the study is complete the study records will be 
transferred to the University of Arizona storage facility and kept in accordance with applicable 

laws. All participant data (including signed informed consent) will be stored for 6 years after the 
completion of the project. Results from this study will be disseminated through peer-reviewed 
manuscripts and presentations at national meetings. Participants will be provided with a lay 
summary of the research findings and the peer reviewed manuscripts.  
 
 
List of Abbreviations:  
Center of Disease Control (CDC)  
Body mass index (BMI) 
Epigallocatechin gallate (EGCG), 
Sugar-sweetened beverages (SSBs) 
hs-CRP (high-sensitivity C-reactive protein)  
HDL (high-density lipoprotein) 
LDL (low-density lipoprotein) 
VLDL (very low-density lipoprotein) 
HbA1c (Hemoglobin A1c)  
Alantine transaminase (ALT) 
Aspartate transaminase (AST) 
Blood urea nitrogen (BUN) 
United States Department of Agriculture (USDA) 
 
 
 
 
 
 
 

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