Evaluating the Impact of Personalized Recommendations on Healthy Behaviours and Cardio-metabolic Risk
Phase: NA
Conditions: Health Behavior, Genetic Information, Cardiovascular Risk Factor
Sponsor: Hamilton Health Sciences Corporation

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
1 
Study Purpose and Rationale 
 
Cardiovascular disease (CVD) is a leading cause of death and disability worldwide, 
accounting for 17.9 million deaths and the loss of 348 million disability-adjusted life years in 2015 
alone1. Diabetes and obesity are very strong risk factors for CVD. Individuals with diabetes and 
obesity have an 82.75% life-time risk for developing CVD2. While treatments do exist for both 
obesity (e.g. bariatric surgery) and diabetes (e.g. pharmaceutical control of blood sugar levels), they 
only partially attenuate risk of adverse health outcomes and they do not address prevention and 
upstream causes of cardiovascular diseases, namely sedentary lifestyle and unhealthy diet. Despite 
the known cardiovascular benefits of regular physical activity and having a balanced diet, it has 
proven challenging to change health behaviours towards favourable lifestyles3–5. Indeed, the 
prevalence of obesity is increasing in Canada as less than 80% of adults follow the current 
recommendation of 150 minutes of moderate-to-vigorous physical activity per week and 
approximately less than 60% of adults consume fruits and vegetables 5 or more times a day6,7. The 
overarching aim of our study is to test the effect of providing personalized genetic information along 
with diet and exercise plans on adherence to healthy lifestyle habits and cardio-metabolic risk. There 
is tremendous public interest in genetics and some evidence that providing genetic information can 
help improve health habits8. However, no intervention to date has examined the effect of 
comprehensive genetic testing using cutting-edge polygenic score (PGS) prediction and an 
interactive health portal on health behaviours and cardio-metabolic risk. 
 
Hypothesis and Objectives 
 
We hypothesize that providing participants with detailed genetic information about genetic 
determinants of fitness and nutrition traits will help motivate them to adopt healthy lifestyle habits. 
Our primary objective is to test the effect of providing genetic information and interactive 
recommendations for diet and exercise on adoption of healthy behaviours. Our secondary objective is 
to evaluate the effects of the personalized health recommendations on cardio-metabolic risk markers, 
such as dysglycemia and dyslipidemia.  
 
Study Design 
 
We propose to conduct a randomized controlled trial investigating whether personalized 
lifestyle recommendations including genetic information motivates Hamilton Health Sciences 
employees to adopt healthy lifestyle changes. Study participation will be open to all Hamilton Health 
Sciences employees. Eligible and consenting individuals will be enrolled starting in March 2017. 
Enrollment will occur in a staggered fashion. The intervention group will receive (1) a free 3-month 
GoodLife Fitness gym membership providing access to any Canadian GoodLife Fitness facility, (2) 
professional trainer-approved workout plans, (3) dietitian-approved meal plans, and (4) genetic 
information pertaining to their health and fitness. The control group will also receive a GoodLife 
Fitness membership to ensure that all study participants are granted similar ease-of-access to perform 
physical activities but will not receive the personalized component of the intervention (workout 
plans, meal plans or genetic information) until the end of their trial period. Participants will be 
randomized to treatment or control groups using a minimization scheme for adaptive randomization, 
which will serve to balance age, gender, and ethnicity across groups as participants are enrolled. 
Thus, randomization will be performed in a single-blind fashion wherein the study team is unaware 
of whom is receiving the intervention or control. All study participants will be monitored over the 
course of 3 months beginning with their baseline assessment and ending with their 3-month follow-
up assessment. At these two timepoints, study participants will be assessed for behavioural (physical 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
2 
activity levels and diet healthiness) and biological markers (lipoproteins, fasting glucose, and 
inflammation) of cardio-metabolic disease.  
 
Trial Population  
 
The trial will enrol healthy adults (18-65 years) that are employed by any Hamilton Health 
Sciences site (Chedoke, Hamilton General Hospital, Juravinski Hospital, Juravinski Cancer Centre, 
McMaster University Medical Centre, McMaster Children’s Hospital, West Lincoln Memorial 
Hospital, St. Peter’s Hospital). Individuals will be excluded from the trial if (1) they are unable to or 
express an unwillingness to comply with core components of our study protocol (i.e. blood draws, 
fitness assessments, diet plan, workout plan) or if (2) they have a cardiovascular disease or insulin-
dependent diabetes. See Table 1 for the full eligibility questionnaire form and schema. There could 
be a delay between the time when someone completes the eligibility questionnaire form and the time 
of official enrollment. As such, potential study participants will be told to contact the study team 
should any of their responses to the eligibility questionnaire change and will also be prompted before 
performing their baseline assessment (data collection sheet, blood draw, and fitness assessment).  
 
Table 1. Eligibility Questionnaire Form  
 
Number 
Question 
Exclude if 
response is: 
1 
Are you employed by Hamilton Health Sciences? 
No 
2 
Would you be willing to attend a GoodLife Fitness centre in Hamilton or Ancaster? 
No 
3 
Are you planning to take vacation for more than 2 weeks from May 1, 2018 to July 31, 2018? 
Yes 
4 
Are you currently pregnant, breastfeeding or planning to be pregnant from May 1, 2018 to 
July 31, 2018? 
Yes 
5 
Are you currently taking insulin? 
Yes 
6 
Have you ever had a bone marrow transplant? 
Yes 
7 
Have you ever had a stroke, heart attack, coronary artery bypass graft (CABG) surgery, 
peripheral artery disease, or coronary angioplasty? 
Yes 
8 
Are you currently taking any of the following medications:  
blood thinners (e.g. warfarin), ACE inhibitors (e.g. captopril, enalapril, lisinopril, moexipril, 
quinapril, ramipril), antibiotics (e.g. linezolid), antidepressants (e.g. phenelzine, 
tranylcypromine) 
Yes 
9a 
One aspect of lifestyle that we are hoping to enhance is physical fitness. If you participate in 
the trial, you will receive a personalized workout plan. Are you willing to comply to a trainer-
approved workout plan from May 1, 2018 to July 31, 2018? 
No 
9b 
Are you willing to perform two physical fitness assessments (baseline and 3 months later)? 
No 
9c 
Do you currently have any conditions that restrict your ability to exercise regularly (e.g. 
osteoarthritis, knee injury, chronic back pain, arrhythmia)? 
Yes 
10a 
If you participate in the DNAble trial, you will receive a personalized meal plan. Are you willing 
to comply to a dietician-approved meal plan from May 1, 2018 to July 31, 2018? 
No 
10b 
Do you currently have any dietary restrictions due to food sensitivities (e.g. gluten, soy, 
peanuts, eggs, shellfish, etc.), preferences (e.g. vegetarianism, veganism), or medical 
conditions (e.g. Crohn's disease, bulimia nervosa)? 
Yes 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
3 
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Blood biomarkers, such as lipid and fasting glucose levels, will be tested to monitor changes 
in your cardiovascular health. Are you willing to have blood testing performed by a medical 
professional in a hospital setting on two separate occasions: at baseline and 3 months later? 
No 
Participant Benefits and Risks 
 
 
The major incentive for Hamilton Health Sciences employees to participate in this trial is that 
they will be equipped with new tools designed to improve their fitness and dietary habits. 
Specifically, study participants will receive personalized exercise plans, meal plans, a 3-month 
GoodLife Fitness gym membership, and their genetic results. Conversely, major risks of participating 
in this trial include unintended disclosure of personal information and injury from performing 
exercises. Protocols have been built-in to reduce mitigate these risks and are detailed in subsequent 
sections. In accordance with Good Clinical Practice, all study participants may exert their right to 
withdraw from the trial at any point in time for any reason with no obligation to reveal the reason for 
discontinuation.  
 
Study Methodology & Workflow 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
4 
 
 
Figure 1. DNAble study workflow.  
 
Advertising, Marketing, Recruitment 
 
The study will be marketed exclusively to Hamilton Health Science employees. All 
marketing materials will indicate that the study is supported by HHS and Ted Scott, HHS Chief 
Innovation Officer of Strategy. In an attempt to reach as many HHS staff as we can, we will 
collaborate with the HHS Public Relations and Communications department. We plan on using 
channels such as employee email advertisements, employee wellness programs and the employee 
incentive discount program to maximize exposure. We also plan to advertise through social media 
platforms, such as the HHS staff (@HHS_staff), and HHS-IBM Innovation 
Exchange(@HHS_innovationX) twitter accounts. Finally, we will employ flyers and posters to 
advertise to staff on billboards in HHS hospitals and facilities. As part of our recruitment strategy, 
each participant will receive a free 3-month membership to any GoodLife Fitness centre in Canada 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
5 
and a complimentary GeneBlueprint genetic test. Please find in the attached email: Email 
Recruitment Script, Recruitment Poster Sample and online Registration landing page 
(https://geneblueprint.com/pages/gbp-hhs-trial-signup2).  
 
Eligibility, Consent, and Enrollment 
 
An electronic questionnaire form will be sent to all individuals that have expressed interest in 
participating in the trial. This questionnaire will determine their eligibility for trial participation. 
Individuals that meet all eligibility requirements will be provided with (1) a study information sheet 
providing further details about the trial (e.g. information on the intervention) and (2) consent form. 
To allow for timely collection of informed consent data from multiple centres, we propose to 
administer consent through an electronic form. Electronic informed consent will adhere to guidelines 
outlined by the FDA (https://www.fda.gov/downloads/drugs/guidances/ucm436811.pdf). As with 
paper consent, individuals will be asked to initial, date, and sign each section of the consent form. A 
member of the trial team will be available Monday to Friday during work hours to answer any 
questions or concerns about the consent form or study via telephone and e-mail. Paper consent forms 
will also be made available at each study site if individuals are uncomfortable with electronic 
consent. The first 500 eligible and consenting individuals will be selected for participation in the 
trial. Subsequently, a follow-up questionnaire gathering demographic information for the purposes of 
logistical planning and to help to inform the randomization scheme will be issued.  
 
Baseline Assessment 
 
The baseline assessment will be identical for participants assigned to either the intervention 
or control group and will consist of: (1) completing the study report form, (2) a blood draw which 
will provide biological material for laboratory testing, (3) and a low-risk fitness assessment which 
does not involve any physical activity. The study report form will collect information pertaining to 
demographics, medical history, dietary habits, physical activity levels, mental health and wellbeing, 
as well as attitudes, feelings, and competency regarding genetic testing. The fitness assessment will 
involve a simple series of measurements including central adiposity (waste-to-hip ratio), heart rate, 
blood pressure, and strength (e.g. calf circumference, bicep circumference). To eliminate any 
possibility of assessment bias during the first assessment, intervention assignment will not occur until 
after the baseline assessment has been completed.  
 
Randomization  
 
Participants will be randomized to intervention or control groups using a minimization 
scheme which will adaptively weight probabilities of treatment assignment based on the distribution 
of age (> 40 vs. < 40), gender (male vs. female), and ethnicity (European/African/East Asian/South 
Asian/Latino/Other). This design has been adopted to minimize unintended covariate biases, which 
can plague smaller trials. Randomization will be implemented through a centralized database. The 
intervention will be delivered via automated e-mails, minimizing direct personal contact with the 
intervention group. 
 
Controls 
 
Upon completion of all three components of the baseline assessment, the control group will 
receive access to a GoodLife fitness centre of their choosing or if not specified, the location nearest 
to their home. For safety purposes, an orientation will be provided by GoodLife Fitness staff to all 
study participants. This will serve to demonstrate best practices within the gym, including how to 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
6 
properly operate the fitness equipment, what the appropriate footwear and workout attire is, and 
general operating rules within the gym. To further ensure the safety of study participants when 
exercising, it will be emphasized that (1) exercises should be performed with some form of 
supervision when attempting a new exercise or heavy weight (e.g. a GoodLife Fitness staff member 
to spot), (2) to never perform types of exercises they may be uncomfortable with, and (3) to never 
attempt to exercise using an excessive amount of weight. Study participants may also consult 
GoodLife Fitness staff if they have questions about how to perform a specific exercise.  
 
Intervention 
 
In addition to a free gym membership for the duration of the trial (all participants, 
irrespective of randomization, will receive a free gym membership), the intervention group will 
receive (1) their genetic results, (2) personalized workout plan and (3) personalized meal plans, all of 
which will be delivered through a secure web portal accessible via smartphone or computer. See the 
“data privacy and security” section below for details regarding specific security measures for the web 
portal. 
 
The genetic results provided to study participants will consist of scores ranging from 0 to 100 
based on the population percentile of the combined effects of many (up to several hundreds of 
thousand) genetic variants, herein referred to as polygenic scores (PGS). The aim of the PGS is to 
provide participants with entertaining yet scientifically sound and accurate genetic information to 
encourage the pursuit of healthy living and identify healthy lifestyle habits that best fit each 
individual. PGS for approximately twenty traits related to health, fitness and nutrition will be 
provided to study participants. These traits are chosen for their relevance to healthy lifestyle habits 
(e.g. genetic predisposition to adiposity or muscle strength), entertainment value (e.g. preference for 
mornings) or both (e.g. bitterness taste perception, which while entertaining can also help guide 
vegetable choices). None of the PGS are diagnostic and are therefore not medically actionable.  
 
The personalized workout plan includes 5 x 30-minute exercise programs per week, which is 
in line with the Canadian recommendation of 150 minutes of moderate to vigorous physical activity 
per week. The programs will propose a set of specific exercises to perform including the number of 
sets and repetitions. All workout programs have been approved by GoodLife Fitness and developed 
by a professional trainer to the UK Olympic team and sports scientist, Nicholas Jones. Through the 
web platform, instructional videos describing and showing how to perform each exercise will be 
made available. It will be emphasized that if at any point a study participant feels uncomfortable with 
an exercise, the participant should consult an on-site personal trainer or forego the exercise 
altogether.  
 
The personalized meal plans are approved by a registered dietician and are consistent with 
the Canadian recommended dietary allowances (RDA). If new, unexpected food allergies develop 
throughout the course of the trial, these will be taken into consideration and dietary recommendations 
for this particular individual will be adjusted immediately. Depending on the severity of the allergy, 
the study participant may be referred to a doctor for allergy testing.  
 
Final assessment  
 
The 3-month follow-up assessment will be identical for participants assigned to either the 
intervention or control group and will consist of: (1) completing the exit study report form, (2) a 
blood draw which will provide biological material for laboratory testing, and (3) a low-risk fitness 
assessment which does not involve any physical activity (Table 2). The exit study report form will 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
7 
strongly resemble the original baseline study report form and query information pertaining to 
demographics, medical history, dietary composition, physical activity levels, mental health and 
wellbeing, as well as attitudes, feelings, and competency regarding genetic testing. Laboratory testing 
will not include genetic testing (as this would be completed using the blood samples collected at 
baseline) but will include testing of lipoproteins, fasting glucose, and inflammatory markers as 
conducted in the baseline assessment.  
 
To incentivize study participants to complete their final assessment, they will receive: 1) an 
additional month’s worth of exercise and meal plans and 2) a lifetime subscription to the 
GeneBlueprint web portal which will be updated with new genetic prediction scores and health tools 
over time. Furthermore, individuals in the control group will be provided access to their genetic 
results, personalized meal plan, and personalized workout plan upon trial completion.  
 
Endpoints  
 
The primary endpoints will be changes in physical activity levels and healthy diet score from 
baseline to 3-month follow-up. Physical activity levels will be quantified based on survey responses 
to the following questions: (1) “In the last 3 months, how many times per week did you perform 
aerobic exercises?” and (2) “In the last 3 months, how many times per week did you perform strength 
training?” These two questions align with recommendations from the Canadian Physical 
Activity Guidelines, which split exercise into the two domains of aerobic exercise (150 minutes of 
moderate to vigorous activity per week) and strength training (2x per week). Dietary healthiness will 
be ascertained using the dietary risk score developed by the INTERHEART study which was found 
to explain 30% of the population attributable risk for acute myocardial infarction10. Briefly, the 
dietary risk score takes into account consumption of meat, salty snacks, fried foods, fruits and 
vegetables. Secondary endpoints will include cardio-metabolic markers (triglycerides, C-reactive 
protein, fasting glucose, blood pressure), measures of fitness (waist-to-hip ratio, circumference of 
thigh, calf, and bicep, body fat percentage) and cardio-metabolic risk as estimated by the validated 
INTERHEART modified risk score (IHMRS)11.  
 
Measurements and measurement instruments 
 
a) Fitness and Physiologic Measurements 
 
The same measurements will be taken at baseline and at 3-month follow-up (Table 2).  
 
Table 2. Fitness and physiologic attributes and the corresponding measurement device.  
 
Measurement(s) 
Device 
Systolic & Diastolic Blood Pressure Sphygmomanometer 
Resting Heart Rate 
Stopwatch/Timer 
Body Fat Percentage 
Scale 
Weight 
Scale 
Waist-to-Hip Ratio 
Myotape measure 
Circumference of thigh, calf, bicep, 
neck, and shoulder span 
Myotape measure 
 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
8 
b) Blood Collection & Laboratory Testing 
 
The Hamilton Regional Laboratory Medicine Program (HRLMP) Core Labs at each HHS site 
will assist in blood collection. All blood samples will be transported to the Clinical Research 
Laboratory & Biobank (CRLB) for subsequent testing. At the CRLB, testing will be conducted for 
(1) lipids (LDL-cholesterol, HDL-cholesterol, total cholesterol, and triglycerides), (2) fasting 
glucose, (3) C-reactive protein, and (4) DNA extraction. See Table 3 below for a comprehensive list 
of blood collection items and the subsequent tests for which they will be allotted. The same 
laboratory tests will be conducted at baseline and 3-month follow-up except for genetic testing which 
will only be performed once at baseline. In addition to blood, we will also collect buccal (cheek) cells 
using a non-invasive cheek swab. 
 
After DNA extraction, samples will be sent to the Genetic Molecular Epidemiology Lab 
(GMEL) for genetic testing. The GMEL is a state-of-the-art genomics centre directed by Dr. 
Guillaume Paré with a plethora of experience having processed more than 120,000 samples using a 
variety of genetic testing methods. For each individual, we will test for 920,576 genetic variants 
using the Axiom PMRA microarray. The primary genetic data will form the basis for calculating for 
the genetic prediction scores for health and wellness traits, referred to as polygenic scores (PGS).  
 
Table 3. List of blood collection tube types and laboratory tests.  
 
Blood Collection Tube 
Laboratory Test 
1 x 4 ml EDTA tube (purple top) 
Genetic testing 
1 x 6 ml plain tube (red top) 
Lipids (LDL/HDL/Total cholesterol, triglycerides) 
 
Dysglycemia (Fasting glucose) 
1 x 4 ml lithium heparin tube (green top) 
Inflammatory Markers (C-reactive Protein [CRP]) 
 
Data Analysis Plan 
 
Overview 
 
All analyses conducted will follow the “Intention-to-treat” (ITT) principle to avoid biases due 
to differential adherence or loss-to-follow-up. In other words, no post-hoc exclusions will be made; 
study participants will be analyzed according to the group to which they were initially assigned even 
if they did not receive the intended treatment (e.g. due to injury during trial period impeding ability 
to exercise) or did not comply. Descriptive characteristics of each group will be summarized as the 
mean, standard deviation and 95% confidence-interval for continuous variables and using 
frequencies and percentages for categorical variables. Statistical tests will be two-sided, and 
between-group comparisons will be presented with 95% confidence intervals where possible. The 
statistical significance level set will vary depending on the number of statistical tests performed. 
Multiple hypotheses testing will be adjusted for within analyses of primary and secondary endpoints 
using a Bonferroni-corrected p-value threshold.  
 
Baseline characteristics 
Baseline characteristics will be compared using univariate regression to assess the balance of 
key risk factors between the intervention and control groups. Linear regression will be applied for 
continuous variables (age, blood pressure, waist-to-hip ratio, body fat percentage, total weekly 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
9 
physical activity level, and dietary risk score) logistic regression for dichotomous variables (gender, 
smoking status, diabetes, dyslipidemia), and analysis of covariance (ANCOVA) will be applied for 
categorical variables exceeding two factor levels (ethnicity, hospital site). Intervention status will be 
the independent variable in the regression model. Differences in the mean or proportion of categories 
between groups will be considered statistically significant if the P-value is less than 0.05. 
Primary Endpoints 
 
The primary endpoints are changes in physical activity levels as well as dietary risk score 
(DRS) from baseline to follow-up. Between-group differences in primary endpoints will be evaluated 
through linear regression. Weekly physical activity level will be represented as a continuous variable 
(frequency of strength training and aerobic exercise per week) for the primary analysis. Baseline 
characteristics found to be differentially distributed between intervention and control groups will be 
included as covariates in subsequent models. Between-group differences for changes in dietary risk 
score will be assessed through linear regression again adjusting for covariates. The significance 
threshold for physical activity levels and dietary health will be 0.025 given that two primary 
endpoints are tested. 
 
Subgroup analysis will be conducted to explore whether changes in dietary health and 
physical activity levels differ based on key strata (age > 40 vs. age < 40, ethnicity, gender, baseline 
low/med/high physical activity levels and baseline dietary risk score tertiles). For example, it is 
conceivable that individuals who begin with the lowest activity levels and least healthy diets have the 
derive more benefit from personalized health recommendations, whereas others who already adhere 
to healthy lifestyle behaviours may have an attenuated response to our intervention.  
 
Secondary Endpoints 
 
Between-group differences in changes in levels of dyslipidemia (triglycerides), dysglycemia 
(fasting glucose), inflammation (C-reactive protein), blood pressure, measures of fitness (waist-to-hip 
ratio, circumference of thigh, calf, and bicep, body fat percentage) and overall cardio-metabolic risk 
as estimated by IHMRS will be analyzed using linear regression. Model covariates will include any 
baseline characteristics found to be differentially distributed between intervention and control 
groups. These analyses are considered exploratory and the significance threshold will thus be set at 
0.05 for suggestive association and 0.005 (i.e. Bonferroni correction for 10 tests) for definitive 
association.  
 
Technical Considerations  
 
All statistical analyses will be conducted in R version 3.4.0. Outlying values exceeding four 
standard deviations will be winsorized or removed if due to a data entry error. If a continuous 
variable is not normally distributed, then log transformation or quantile normalization will be 
applied. Missing values for continuous variables will be imputed based on the mean value across all 
samples with non-missing values including both intervention and control groups. For categorical 
variables, missing values will be imputed using the proportion of non-missing samples belonging to a 
given factor level to define the probability of assigning a study participant to that factor level.  
 
Power Calculations 
 
At a sample size of 500 participants (250 intervention and 250 control group), we estimate 
that we will have 90% power to detect a difference of 0.32 standard deviations between intervention 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
10
and control groups (alpha=0.025). An alpha of 0.025 is used in lieu of the traditional value of 0.05 in 
order to account for multiple hypotheses testing of the two primary endpoints (physical activity and 
diet risk score). For physical activity, this is equivalent to a difference in ~50 MET-min/wk which 
translates to a difference of 12.5 minutes of moderate exercise or 6.75 minutes of vigorous exercise 
per week9. This power calculation is based on the work by Jurakic et al. (2009) who estimated 
average weekly physical activity levels in adult Croatians to be 3492 MET-min (SD=162.25) using 
the same validated questionnaire that will be used in the present trial12. The translation of the dietary 
risk score is less straight-forward as the scoring system is comprised of disparate food habits that best 
predict acute myocardial infarction (e.g. salty meat vs. cooked vegetables). Granted, we will be well-
powered to detect a 0.32 standard deviation in INTERHEART dietary risk score between 
intervention and control groups at alpha=0.025.  
 
Data Security & Privacy 
 
Primary genetic data is defined as an individual’s genotypic state generated directly from a 
laboratory instrument. Primary genetic data is highly sensitive personal information as it represents 
an individual’s genetic code. Consequently, strict security measures will be employed to safeguard 
these data and mitigate the risk of confidentiality breach:  
 
(1) The primary genetic data for every study participant is stored on a secured server managed by the 
Information & Communications Technology (ICT) Team at Hamilton Health Sciences (HHS). HHS 
servers are secured using industry best standards, including nightly backups, high-end firewall 
systems, regular monitoring to ensure that any vulnerabilities are quickly found and patched.  
 
(2) The primary genetic data comprising nearly a million genetic data points are used as the building 
blocks for the PGS. PGS are generated using a sophisticated algorithm to consolidate information 
from many genetic variants into a single numerical value. Having knowledge of the algorithm and 
the specific set of genetic variants that comprise the PGS is not sufficient to deduce a participant’s 
primary genetic data, as there is a multiplicity of combinations that could lead to the same overall 
numerical score. In other words, it is impossible to deduce an individual’s primary genetic data using 
the PGS. Only the PGS will be transferred to the web portal server. Importantly, no identifying 
information (i.e. name, email address, address, etc.) will ever be stored on the same server as the 
primary genetic data. Primary genetic data for each participant will be issued its own randomized ID 
number, different from the participants study ID (i.e. double de-identification). The key linking both 
numbers will be kept in a secure computer different from the genetic server, minimizing the risk of a 
catastrophic hack. 
 
(3) The GeneBlueprint web portal provides a secure means for participants to access and learn about 
the genetic basis of their health and wellness. There is minimal risk of participant de-identification. 
The web portal is password protected and this password is only known to the study participant. 
Information regarding an individual’s genotype at selected (~30) genetic variants will be provided for 
educational purposes in the form of a “Top Gene Contribution Table”; however, there is minimal risk 
of de-identification as these genetic variants are commonly prevalent in the general population. 
Essentially, it is impossible to re-identify a participant if the identifying feature is common, such as 
hair color to use an analogy. Additionally, the website itself employs many security measures to 
prevent prohibited access or disclosure through various physical, technical, and administrative 
means. All connections to the GeneBlueprint website (https://geneblueprint.com) are encrypted using 
Secure Socket Layer (SSL) technology. Security and privacy of personal information maintained on 
the GeneBlueprint portal will adhere to both Canadian (Personal Information Protection and 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
11
Electronic Documents Act) and US (Health Information Portability and Accountability Act) 
legislation. 
 
 
It should also be noted that personal genetic information will not be disseminated to 
employers or insurers as per Canadian law. The privacy of study participant’s genetic information is 
protected by the “Genetic Non-Discrimination Act” which was passed May 4, 2017. This law 
prohibits employers and insurers from requiring someone to conducting genetic testing or disclose 
findings from existing genetic test results as a condition of (1) providing good and services to that 
individual, (2) entering into or continuing a contract or agreement with that individual, or (3) offering 
or continuing specific terms or conditions in a contract or agreement with that individual (http://laws-
lois.justice.gc.ca/eng/acts/G-2.5/page-1.html#h-1).  
 
Incidental Findings.  
 
Laboratory Results 
 
Blood testing results at baseline and 3-months follow-up could reveal medical diagnoses 
unbeknownst to the study partiycipant that warrant disclosure. Such findings include but are not 
limited to diabetes (fasting glucose > 7 mmol/L), hypercholesterolemia (LDLc > 5 mmol/L), and 
hypertriglyceridemia (triglycerides > 10 mmol/L). Upon identification of an aberrant test result, 
confirmatory testing will be expedited through the Hamilton Regional Laboratory Medicine Program, 
which consists of several clinical laboratories approved by the Ontario Ministry of Health. 
Confirmatory testing will help mitigate the risk of false-positives, a potential source of unnecessary 
anxiety and stress for study participants. Once confirmatory testing validates the initial positive 
result, the study participant will be contacted by trial management and referred to the appropriate 
medical specialist (e.g. endocrinologist or lipid specialist). Continuation in the trial will be based on 
the physician’s discretion as well as the willingness of the study participant. 
 
Genetic Results 
 
There is no risk of incidentally discovering medically actionable genetic conditions or 
disorders as this is beyond the scope of this project. While the American College of Medical 
Geneticists (ACMG) has recommended reporting pathogenic mutations within 65 genes that may 
cause conditions unrelated to the primary indications13, these recommendations specifically apply to 
studies involving clinical exome or genome sequencing. Our study does not involve clinical exome 
or genome sequencing and the proposed method is unable to detect variants of diagnostic value. 
Therefore, there is no risk of genetic incidental findings.  
 
Fitness Assessment 
 
Extremely elevated resting heart rate and blood pressure are contraindications for exercise. 
Incidental discovery of previously undiagnosed malignant hypertension (SBP > 180/120 mmhg) or 
tachycardia (resting heart rate > 100 bpm) during the baseline fitness assessment will preclude an 
individual from continuing with the fitness portion of the trial. Malignant hypertension is a medical 
emergency and anyone identified with this condition will be referred to the hospital immediately. 
Study participants identified with tachycardia will be referred to an appropriate health professional.  
 
References 
 
1. 
Roth, G. A. et al. Global, Regional, and National Burden of Cardiovascular Diseases for 

Primary Applicant: Guillaume Pare, MD, FRCPC; Project Title: Evaluating the impact of personalized health recommendations on 
lifestyle behaviours and cardio-metabolic risk: The DNA-based life style enhancement (DNAble)Trial 
 
12
10 Causes, 1990 to 2015. J. Am. Coll. Cardiol. 70, 1–25 (2017). 
2. 
Fox, C. S. et al. Lifetime risk of cardiovascular disease among individuals with and 
without diabetes stratified by obesity status in the Framingham heart study. Diabetes Care 
31, 1582–4 (2008). 
3. 
Teo, K. et al. Prevalence of a healthy lifestyle among individuals with cardiovascular 
disease in high-, middle- and low-income countries: The Prospective Urban Rural 
Epidemiology (PURE) study. JAMA 309, 1613–21 (2013). 
4. 
Yusuf, S. et al. Effect of potentially modifiable risk factors associated with myocardial 
infarction in 52 countries (the INTERHEART study): case-control study. Lancet (London, 
England) 364, 937–52 
5. 
O’Donnell, M. J. et al. Global and regional effects of potentially modifiable risk factors 
associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. 
Lancet (London, England) 388, 761–75 (2016). 
6. 
Statistics Canada. Distribution of the household population meeting/not meeting the 
Canadian physical activity guidelines, by sex and age group, occasional (percentage). 
Table 117-, (2015). 
7. 
Statistics Canada. Fruit and vegetable consumption, 5 times or more per day, by age 
group and sex (Percentage). (2016). 
8. 
Kullo, I. J. et al. Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk 
Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES 
Clinical Trial). Circulation 133, 1181–8 (2016). 
9. 
Hagströmer, M., Oja, P. & Sjöström, M. The International Physical Activity Questionnaire 
(IPAQ): a study of concurrent and construct validity. Public Health Nutr. 9, 755–62 
(2006). 
10. 
Iqbal, R. et al. Dietary patterns and the risk of acute myocardial infarction in 52 countries: 
results of the INTERHEART study. Circulation 118, 1929–37 (2008). 
11. 
McGorrian, C. et al. Estimating modifiable coronary heart disease risk in multiple regions 
of the world: the INTERHEART Modifiable Risk Score. Eur. Heart J. 32, 581–9 (2011). 
12. 
Jurakić, D., Pedisić, Z. & Andrijasević, M. Physical activity of Croatian population: cross-
sectional study using International Physical Activity Questionnaire. Croat. Med. J. 50, 
165–73 (2009). 
13. 
Kalia, S. S. et al. Recommendations for reporting of secondary findings in clinical exome 
and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the 
American College of Medical Genetics and Genomics. Genet. Med. 19, 249–255 (2017).