Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03447340 |
| Other study ID # |
2000027132 |
| Secondary ID |
7DP1ES025459-05 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 9, 2016 |
| Est. completion date |
December 9, 2022 |
Study information
| Verified date |
October 2023 |
| Source |
Yale University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The proposed project will develop, implement, and test methodology for the design of an
acceptable, effective intervention for diabetes prevention in a real-world setting. By
determining the effectiveness of the intervention, the study will serve to guide the
translation of research into routine public health prevention programs and policy. And, the
hands-on experience will directly support the development of expertise, tools and training to
advance translational science as a discipline. The study aims to test the effectiveness of an
environmental and individual level intervention to prevent diabetes at Dhulikhel
Hospital-Kathmandu University Hospital (DH-KUH), Nepal. Specific aims are to measure:
Effectiveness of a canteen intervention on a composite score based upon improvement in 3
cardio-metabolic risk factors (0-3) [HbA1c decrease ≥0.5%; a systolic blood pressure decrease
(SBP) ≥5 mm Hg; and plasma triglycerides decrease ≥10 mg/dl] Effectiveness of a behavioral
intervention on a composite score based upon improvement in 3 cardio-metabolic risk factors
(0-3) [HbA1c decrease ≥0.5%; SBP decrease ≥5 mm Hg; and plasma triglycerides decrease ≥10
mg/dl] Effectiveness of a canteen intervention on change in HbA1C and healthy food intake
after six months of the canteen only (CO) intervention compared to the change over six months
during the control period.
Effectiveness of a behavioral intervention on change in Hba1c and healthy food intake after
six months of behavioral intervention plus the canteen (CB) intervention compared to the
change over six months during CO.
We will recruit 366 adult employees of DH-KUH. At baseline (T1), 6 months (T2), 12 months
(T3) and 18 months (T4), we will administer a standard questionnaire to record relevant
characteristics of the participants (age, sex, education, income, marital status, and family
history of CVD, physical activity, smoking, alcohol intake and diet). We will abstract food
consumption data from the administrative database in DH-KUH. Blood samples will be collected
and analyzed for HbA1c, fasting glucose, and lipid profile (HDL, LDL, total cholesterol,
triglycerides). We will measure height, weight, waist circumference, hip circumference, and
blood pressure. After 6 months of control period, the participants will receive the canteen
intervention: (a) form and train a canteen improvement team; (b) train canteen staff on
healthy cooking; (c) add healthy food and remove unhealthy food; (d) information and
communication of canteen changes to employees; (e) monitoring of the interventions. After six
months of the canteen intervention, half of the participants will be randomized to receive
the behavioral intervention. The behavior intervention will be a combination of intensive
education sessions, group counselling, goal setting and monitoring based on the Diabetes
Prevention Program (DPP). The primary analysis will use χ^2test use to compare (a) Proportion
of individual with score ≥ 2 during CO intervention to the proportion of individual with
score ≥ 2 during the control period; (b) Proportion of individual with score ≥ 2 during CB
intervention to the proportion of individual with score ≥ 2 during CO intervention. We will
conduct a logistic regression with the proportion of individual with score ≥ 2 as outcome and
CO vs CB as exposure at T4. Secondary analysis will use paired t-test to compare (a) the
change in healthy food intake and HbA1c during CO to the change in healthy food intake and
HbA1C during the control period (b) the change in healthy food intake and HbA1C% during CB to
the change in healthy food intake and HbA1C% during CO period. We will conduct linear
regression with HbA1c% as the outcome and CO vs CB as the exposure variable at T4. Further
analysis will adjust for confounding in time-varying variables and assess effect
modification.
Description:
INTRODUCTION
The burden of non-communicable diseases (NCDs), such as cardiovascular disease (CVD),
diabetes, cancer, and chronic obstructive pulmonary disease (COPD),are on the rise in low-
and middle- income countries. CVD is the leading cause of morbidity, mortality, and
disability in South Asia, where 20% of the world's population resides.
Sedentary lifestyle, poor diet, and excessive body weight are reported to have a large effect
on the risk of developing NCD's. Lifestyle interventions addressing diet and exercise have
reduced cardiovascular risk. Despite the evidence supporting the use of lifestyle
interventions to prevent hypertension and diabetes and to improve glucose tolerance, their
translation into real world settings has been challenging. Worksites provide unique
opportunities for health promotion and disease prevention programs since people spend a
majority of their time at work, and they allow access to large segments of the population.
Worksites also provide an infrastructure and natural environment for social support.
Worksite-based health programs have shown positive impacts on employee health, and they have
shown significant improvements in cardiovascular risk factor profiles. Worksite interventions
encompassing environmental changes (i.e. low-cost healthy food options), places for physical
activity (i.e. fitness centers or gyms), , and group-based health education classes, have
been highlighted as components of successful worksite interventions. As an important way to
translate CVD prevention efforts, worksite interventions can promote healthy food choices,
facilitate health education, and provide social support. Thus, we planned a pioneer study
that will measure the effectiveness of a cafeteria-based intervention and a behavioral
intervention on cardio-metabolic risk among employees of a hospital based in Nepal, by
evaluating the change in number of individuals reaching two or more cardio-metabolic risk
goals, specifically reductions in blood pressure, triglycerides, and glycosylated hemoglobin
(HbA1c,).
METHODS AND MATERIALS
Study design:
The Nepal Pioneer Worksite Intervention Study is a two-step intervention study. In the first
step, we will use a pre-post design to assess how a cafeteria-based intervention, that
provides a healthier diet, effects cardio-metabolic risk. In the second step, we will conduct
an open-masked, two-arm randomized trial by allocating half of the participants to a
cafeteria and behavioral (CB) intervention on prevention of cardio-metabolic risk, while the
other half of participants will receive the cafeteria-only (CO) intervention. The study
protocol has been approved by the institutional review committee at Harvard T.H. Chan School
of Public Health, Nepal Health Research Council, and Kathmandu University School of Medical
Sciences.
Study Setting:
The study will be conducted at Dhulikhel Hospital -Kathmandu University Hospital (DH-KUH) in
central Nepal. Dhulikhel Hospital is an independently owned, not-for-profit institution which
was conceived and supported by the Dhulikhel community. The hospital has approximately 1040
employees and four functional cafeterias that are in operation 16 hours a day.
Recruitment:
We will conduct a 20-minute information session in all of the hospital departments. Employees
will be invited to attend sessions through flyers posted around the hospital and through
announcements in department meetings. During the information session, we will explain the
purpose and the expectations of the study. We will explain the ethical considerations,
emphasizing the importance of protecting participant's privacy during research-related
interactions and outcomes, the volunteer nature of the study, the option to drop out of the
study at any time and we will establish there should not be any coercion from supervisors to
participate in the study. After the information session, research assistants (RAs) will set
up an appointment for eligibility screening among interested participants.
The inclusion criteria are: (a) adults 18 years or older; (b) full time employees of DH-KUH;
with (c) systolic blood pressure of >=120 mmHg or diastolic pressure >=80 mmHg; or HbA1c of
5.7% to 6.4%, or fasting blood sugar of >=100 mg/dL. The exclusion criteria of the study are:
(a) pregnant women since dietary habits may change during pregnancy, (b) taking diabetes
medication, or (c) taking hypertension medication. The details of the screening process are
described below. The RA will obtain written informed consent in a private room for those
individuals who are deemed eligible to participate in the study. A short oral consent process
will be utilized for participants who cannot read the consent form. This will entail
presenting all of the elements of the consent form verbally to the participant, in the
presence of a witness. The witness will be required to sign a document stating the consent
form has been verbally presented to the participant.
Data collection: The schedule of enrollment and assessment is presented in Table 1.
Screening: The RAs will conduct a 2 phased screening to identify the eligible participants.
In the first screening, the RAs will screen participants by measuring blood pressure, and
administering a questionnaire along with measures to calculate an Indian Diabetes Risk Score
(IDRS).13 The IDRS takes age, abdominal obesity, self-reported physical activity, and family
history of diabetes into account. The IDRS score ranges from 0 to 100, with a high number
indicating higher risk. The IDRS has been considered a reliable instrument to screen the risk
of diabetes in Asian-Indian populations.13 An IDRS of 30 or more has been shown to have 95%
sensitivity and 45% specificity to detect prediabetes using fasting blood sugar criteria
(100-120 mg/dL); and 87% sensitivity and 47% specificity using HbA1c criteria (HbA1c
5.7-6.5%) in an analysis of 560 free residents of Dhulikhel (Unpublished).
Blood pressure will be measured in the right arm of seated participants, after a five- minute
rest period. Three measurements of systolic and diastolic blood pressure will be taken using
a Microlife automatic blood pressure measuring device. The mean of three blood pressure
measurements will be used. The participants with systolic blood pressure of >=120 mmHg or
diastolic pressure >=80 mmHg will be invited to participate regardless of their IDRS score.
In the second screening, the participants scoring 30 or more on IDRS will be asked to provide
a blood sample to measure HbA1c and fasting blood glucose. The individuals with HbA1c between
5.7% to 6.4% or fasting blood sugar of >=100 mg/dL will be invited to participate. All
eligible individuals that provided informed consent will be enrolled. No compensation or
reimbursement will be provided to the participants.
Baseline assessment: At baseline, RAs will interview the participants using a standardized
electronic questionnaire using Open Data Kit software.14 RAs will receive two weeks training
on data collection and ethical issues.
The questionnaire will assess socioeconomic characteristics including age, sex, ethnicity,
religion, marital status, annual income, education, and lifestyle factors including smoking,
alcohol intake, and physical activity. We will use the Global Physical Activity
Questionnaire,15 and calculate the metabolic equivalent of task (MET) minutes per week. A
weekly MET equivalent of 600 would represent 30 minutes of brisk walking five times per week
or 15 minutes of running five times per week.
Twenty four hour diet recall: To measure dietary intake, we will conduct two
interviewer-administered 24-hour dietary recalls within a week. Each 24-hour dietary recall
will take approximately 25 minutes to complete. First, activities of the previous day will be
documented to refresh the participant's memory. Then, a dietitian will ask the participant to
recall everything s/he consumed from the first meal to last meal. The time and place of each
meal will be noted, followed by detailed information on each food including: specific brands,
ingredients, and/or recipes. Participants will be asked to report their food portions using
colorful examples of sizes or household measures such as spoon, bowl, etc. If a participant
reports using their own recipe, then complete information on each individual ingredient will
be inquired about. Energy and nutrient intakes will be calculated using the food composition
table for Nepal.16
Anthropometry: Body weight will be measured with minimum clothing and without shoes using an
Omron Model hbf-400 scale and recorded to the nearest 0.1 pounds. The weighing scale will
calibrated to zero every day. Participants' heights will be measured, without shoes, while
the participants stand against a wall. Height will be measured using a tape measure and
recorded to the nearest 0.1cm.
Laboratory: Blood samples will be analyzed for HbA1c, fasting glucose, low density
lipoprotein (LDL) cholesterol, high density lipoprotein (LDL) cholesterol, triglycerides, and
total cholesterol. All of the laboratory procedures will be carried out in the biochemistry
laboratory of DH-KUH. Blood samples will be collected using evacuated blood collection tubes.
Participants will be asked to fast overnight (8-14 hours). The HbA1c will be measured using
Boronate affinity chromatography (Axis-Shield, Norway); fasting blood glucose using
hexokinase method (Dialab, Austria); LDL and HDL using the elimination method (Dialab,
Austria); triglyceride using gpo-pap (Dialab, Austria); and total cholesterol using chod-pap
(Dialab, Austria). For each type of assay, the laboratory has quality control (QC) materials
(sing commercially available assayed and unassayed control material) from biorad
Laboratories, USA. Each QC is run at least in duplicate. External QC is arranged by
internationally recognized reference laboratories that distribute batches of samples of
various concentrations for each assay. The laboratory performs External Quality Assurance
Scheme from unknown assayed sample from the Department of Clinical Biochemistry, Christine
Medical College, Vellore, India for 23 routine parameters, 5 immunological parameters and
HbA1c. Additionally, 5% of the blood samples will be obtained in duplicates and sent for
testing all parameters, blinded to the laboratory personnel.
Control period: We will have a control period of six months before implementing the
intervention. There will not be any contact with the enrolled participants six months after
the study enrollment. The control period will allow us to conduct the difference in
difference analysis; hence minimizing potential biases in effect size, including increases or
decreases in a health condition with time.
Interventions Step 1: Cafeteria Intervention: After six months of the control period, all of
the participants will receive the cafeteria intervention (Table 2). The cafeteria
intervention was developed based on the findings from four focus group discussions with
cafeteria users and nine in-depth interviews with cafeteria operators and managers, about
strategies to promote healthy foods in the worksite. The four cafeterias in the hospital will
improve the quality of their meals by (1) increasing the availability of fresh fruit (not
fruit juice) and vegetable options, (2) avoiding sales of sugar sweetened beverages, (3)
replacing whole grains with refined grains in cooking; (4) using healthy vegetable oils such
as soy and sunflower ; (5) minimizing the sale of fried foods; (6) trimming animal fats from
meats before cooking; (7) using healthier protein sources such as chicken, beans, and nuts
(8) making potable water free of cost; and (9) reducing salt in cooking. These guidelines are
based on the recommendations for a healthy diet to improve cardiovascular health.22 To
facilitate these changes, a cafeteria operation team will be formed and they will be trained
on procedures to implement, supervise, and monitor the worksite's healthy changes. In
addition, we will train the cafeteria staff on healthy eating, and how to modify recipes to
incorporate healthy options.
Step 2: The behavioral intervention: After six months of the cafeteria intervention, half of
the participants will be randomized using computer generated random numbers to receive a
cafeteria and behavioral intervention (CB), the other half of the participants will continue
to receive the cafeteria only (CO) intervention. The behavioral intervention will be
comprised of intensive education sessions, group counseling, and goal setting and monitoring
exercises based on the Diabetes Prevention Program (DPP)23 tailored to local needs. The
curriculum includes 24 sessions of 16 cores weekly sessions during the first four months of
the intervention followed by 8 weekly maintenance sessions. Each session will be 1 hour long,
facilitated by a dietitian. Broadly, the curriculum covers the subject matters of importance
of healthy weight, eating a healthy diet, increasing physical activity, stress management,
and challenges of lifestyle changes. Similar to the cafeteria intervention, healthy eating
messages include increasing fresh fruits and vegetable intake, avoiding added sugar, choosing
whole grains, choosing healthier sources of protein, reducing sodium, and monitoring portion
sizes. Participants will be encouraged to keep food and activity diaries throughout the
course of the study. The maintenance period's focus will be on overcoming declines in
motivation and maintaining long-term healthy behaviors. All of the sessions will be conducted
at the worksite during the workday. There will be about 20 participants in each education
class. Participants will set a minimum of two lifestyle-change goals (i.e. Half of their
total grain intake will be whole grains, walking 30 minutes a day, or reducing 7% of their
body weight).
Follow up:
We will assess outcomes at 6 months (at the end of the control period), 12 months (at the end
of the cafeteria intervention), and 18 months (at the end of the behavioral intervention).
During each follow up, fasting blood samples will be collected and analyzed for HbA1c,
fasting glucose, and lipid profile (HDL, LDL, total cholesterol, triglycerides). We will
re-administer the global physical activity questionnaire, and the two 24-hour diet recalls.
We will re-measure height, weight, waist circumference, and blood pressure at each time point
Primary and secondary outcomes:
The primary outcome will be the proportion of individuals reaching two or more of their
cardio-metabolic risk goals, namely, reductions in blood pressure, triglycerides, and HbA1c.
Participants will be scored on the number of improved risk factors (0-3) as defined by
decreases in (1) HbA1c ≥0.5%; (2) systolic blood pressure ≥5 mm Hg; or plasma triglycerides
≥10 mg/dl. These outcomes were selected because blood pressure, HbA1c, and triglycerides are
commonly measured in clinical settings. This makes their use clinically-appropriate and
translatable, as other CVD risk scores such as the Framingham Risk Score, do not perform well
in South Asian populations.24 Moreover, the composite outcome allows for individuals to
reduce different factors based on their variable risk profiles at baseline. For example, an
individual with a baseline systolic blood pressure of 120 mmHg many not reduce this risk
factor by as much as 5 mmHg, but may succeed in reducing HbA1c or triglycerides. The
secondary outcomes are absolute changes in HbA1c, systolic blood pressure, diastolic blood
pressure, and triglycerides.
Data Management:
We have taken four robust provisions to ensure data quality. First, the electronic
questionnaire will be closed only if the data collection is complete to avoid partial or
missing values. The data will be cleaned and checked every month. The answer fields for all
integer variables will be constrained to ensure entry of only valid numbers. Second, RAs will
receive intensive training on data collection and ethical considerations. Third, the site
investigator will supervise the RAs on a day-to-day basis. Fourth, the principal
investigators will hold weekly meetings with site investigators, and if required, with the
RAs, to discuss the course of the intervention and to address any issues.
Data Analysis Plan: The primary analysis will be intention to treat. The quantitative data
analysis will follow the Consolidated Standards of Reporting Trials (CONSORT) guidelines.25
Flowcharts will include the number of participants seen at each stage, including the number
screened, eligible, randomized, and analyzed for the primary outcomes.
Effectiveness of the cafeteria intervention: At the 12-month follow-up, we will compare the
proportion of participants who achieved two or more of their cardio-metabolic risk factor
reduction goals during the cafeteria intervention period, to the proportion of participants
in the control period, using the generalized estimating equations (GEE) approach with the
binary distribution, logit link function and an exchangeable working correlation structure.26
Effectiveness of the behavioral intervention: At the 18-month follow-up, we will compare the
proportion of participants who have achieved two or more of their cardio-metabolic risk
factor reduction goals in CO arm to the proportion of participants in the CB arm using
chi-square test. In the event that randomization does not control for differences between the
treatment and control groups on baseline characteristics, we will statistically control for
those differences using the GEE approach with the binary distribution, logit link function
and an exchangeable working correlation structure.26
Our secondary analysis will compare the change in HbA1c, systolic blood pressure, and lipids
during the cafeteria-only intervention to the change during the control period using a paired
t-test. Similarly, we will compare the change in HbA1c, systolic blood pressure, and lipids
between CO group and CB group using a paired t-test. In the event that randomization does not
control for differences between the treatment and control groups on baseline characteristics,
we will conduct the GEE approach with the Gaussian distribution, identity link function and
an exchangeable working correlation matrix26 to adjust for potential confounding factors.
Sample size and power:
The pre-post design, with at least 366 eligible and enrolled participants27 and 5% loss to
follow-up (LTF) after 12 months, will have over 90% of power to detect the primary
effectiveness endpoint of this trial, of 31.5% or greater, compared to the 21% change in the
control group in a South Asian population.28 For the analysis of two randomized groups (CO
and CB arms), with 320 participants, we will be able to detect a relative risk of 1.5 given
0.315 risk probability in the control group, 5% LTF rate with 80% power and 5% level of
significance.29
In the secondary analysis will be the comparison of changes in HbA1c, systolic and diastolic
blood pressure, and lipids observed in the cafeteria intervention and the behavioral
intervention. Given the sample sizes of 366 and 320 respectively, 5% LTF rate with 80% power
and 5% level of significance, we will be able to detect the minimum differences presented in
Table 1. For the before-after design, we considered three possible values of the correlation
(ρ=0.5,0.6,0.7) between changes during the control period and during the intervention period.
Minimization of contamination:
The risk and level of contamination during the randomized study phase for the behavioral
intervention will be monitored at the participant level. The participants will be instructed
not to share information about the study and not to provide any support to people in their
worksite, other than their class mates. The behavioral classes will be conducted in a
separate building outside of their workspace to ensure privacy. Further, we will measure
possible contamination by asking if the participants have received any information / advice
regarding diet and lifestyle changes from any of their peers and if they did, collect the
name and contact information of the peer. If the contamination is found to be significant, we
will make adjustments while estimating the effect.
Intervention fidelity:
Intervention fidelity refers to the extent the intervention is delivered as it was
intended.30 In the proposed study, we will warrant and quantify the fidelity of both the
cafeteria and the behavioral intervention. First, we will provide training sessions on the
study objectives, details of the interventions, and the importance of fidelity to the study
staff, cafeteria improvement committee and cafeteria staff. . Second, we will monitor the
implementation of changes in the cafeteria using a structured checklist on a weekly basis.
The checklist is provided in the supplementary materials. The deviance in fidelity will be
discussed during the monthly meeting of the cafeteria improvement team where necessary action
will be taken. For the behavioral intervention, we will measure attendance from participants
and we will test pre- and post- knowledge on diabetes prevention, covered in the health
education sessions. Finally, a site investigator will supervise the implementation of
intervention.
Interim analyses:
We do not have a plan for interim analysis and do not expect a situation that would lead us
to stop the study. The participants with newly reported pregnancy during the course of the
study will be excluded from the study.
Reportable Events and Indemnities:
Serious adverse events are not expected. Other events related to study participation (such as
an infection at the site of a blood draw clinic, or a breach of confidentiality) will be
documented. All unanticipated problems (non-medical occurrence) that involve risk to subjects
or others will be reported to the institutional review board at Kathmandu School of Medical
Sciences and Harvard T.H. Chan School of Public Health.
