Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05603663 |
| Other study ID # |
Grant #101016775 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 20, 2022 |
| Est. completion date |
January 20, 2024 |
Study information
| Verified date |
October 2022 |
| Source |
University of Tartu |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to evaluate the impact of awareness of high polygenic risk
for CVD on health behavior among young overweight adults. We want to evaluate the impact of
awareness of high polygenic risk for CVD on body mass index within 12 months, the impact of
awareness of high polygenic risk for CVD on other health indicators (physical activity,
systolic blood pressure, cholesterol and triglyceride levels, smoking, waist circumference,
CVD risk score), and assess the cost-effectiveness of informing people about the high
polygenic risk for CVD.
The trial will be conducted in a primary care setting, for which the high genetic-risk
subjects will be invited to visit their family physician. In the course of the first visit,
the family physician will assess the participant's health status and will counsel the
participant on healthy choices for increasing their level of physical activity and losing
weight. If necessary, the family physician will start treatment to lower the participant's
blood pressure or cholesterol following current treatment guidelines. The participants in the
intervention group will be informed of their high polygenic risk for CVD at the start of the
study, while the control subjects at the end of the study. There will be three study visits
at 6-month intervals. Between visits, the participants will receive reminders via a mobile
health application to change their health behavior. At the end of the trial (month 12), the
health indicators of the participants will be assessed and compared between the three trial
groups. If a significant difference in BMI is found, it will presumably be related to the
fact of learning of the high genetic risk, in which case the use of genetic data in primary
prevention may be considered effective.
Description:
Background
Cardiovascular disease (CVD) is the most prevalent cause of mortality. The risk of CVD can be
reduced through effective prevention measures.
The risk of CVD can be assessed using genetic analysis. Large-scale international studies
have shown that CVD is a polygenic disease. Based on the interaction of multiple
single-nucleotide polymorphisms (SNPs) in individuals, a polygenic risk score (PRS)
methodology has been developed for individual risk assessments.
Assessment of polygenic risk for CVD is not yet employed in clinical practice, as it is not
clear whether awareness of high risk motivates health behavior to make healthier choices to
prevent the related illness. Existing research results are contentious. For example, it is
not clear whether informing smokers of their high genetic risk for cancer contributes to
their quitting smoking or whether physical activity increases in individuals with a high PRS
for diabetes after learning of their genetic risk. As the risk of disease in individuals with
a high PRS can be reduced predominantly through healthy choices, knowledge of these issues is
important for the inclusion of PRS in treatment guidelines.
Hypothesis
Learning of high polygenic risk changes people's health behavior, increasing the impact of
personalized primary prevention of CVD.
Aim of the study
The primary objective of the trial is to evaluate the impact of awareness of high polygenic
risk for CVD on health behavior among young overweight adults.
Objectives
1. To evaluate the impact of awareness of high polygenic risk for CVD on body mass index
within 12 months (primary objective).
2. To evaluate the impact of awareness of high polygenic risk for CVD on other health
indicators (physical activity, systolic blood pressure, cholesterol and triglyceride
levels, smoking, waist circumference, and CVD risk score).
3. To evaluate the economic impact of informing people about the high polygenic risk for
CVD.
Outcomes
1. Body mass index
2. Systolic blood pressure
3. Total cholesterol
4. Waist circumference
5. Smoking prevalence
6. Physical activity
7. CVD risk score
At the start and end of the trial, the participating physicians and family nurses will also
be asked for their opinion on the utility of using data about genetic risk for CVD and
genetic feedback (in the form of an anonymous survey).
Study design
To assess the health impacts of learning about the high polygenic risk for CVD, a randomized
controlled trial will be conducted in a primary care setting, under real-life conditions.
The subjects will consist of 1500 individuals aged 25-44 years from the Biobank of the
Estonian Genome Center (EGC) who are overweight and have no previously diagnosed CVD, and who
belong to the top 20th percentile of polygenic risk for CVD (n=1000) and the bottom 20th
percentile of polygenic risk for CVD (n=500). The high-PRS subjects will be randomized to two
study groups, 500 in the intervention group and 500 in the 1st control group. The rest of the
study subjects (500 subjects with low PRS) will be recruited for the 2nd control group from
the Biobank database using matching for age and sex.
The trial will be conducted in a primary care setting, for which the high-PRS subjects from
the intervention group and 1st control group will be invited to visit their family physician.
In the course of the first visit, the family physician will assess the subject's health
status and will counsel the subject on healthy choices for increasing their level of physical
activity and losing weight. If necessary, the family physician will start treatment to lower
the subject's blood pressure or cholesterol following current treatment guidelines. The
subjects in the intervention group will be informed of their high polygenic risk for CVD by
the family physician, while the control subjects will not be informed of the level of their
polygenic risk. There will be three study visits at 6-month intervals. Between visits, the
subjects will receive reminders to change their health behavior via a mobile application. At
the end of the trial (month 12), the BMI, level of physical activity, and other health
indicators of the subjects will be compared between the two trial groups. If a significant
difference in BMI is found, it will presumably be related to the fact of learning of the high
genetic risk, in which case the use of genetic data in primary prevention may be considered
effective.
As the trial will assess the impact of awareness of high genetic risk, the physicians and
controls must be completely blinded to their high genetic risk. To ensure the blinding of the
family physicians, another control group (2nd control group, n=500) consisting of age- and
sex-matched subjects with low CVD PRS are included in the trial. The genetic risk of the
subjects in neither control group will be reported to the family physicians. Both control
groups are mixed for family physicians. Thus, whenever a new control subject enters the
trial, he/she may have either a high or low polygenic risk and the physician will not be able
to distinguish between the two. This design ensures that the physicians are blinded to the
risk of controls, and minimizes the risk of information bias.
The EGC will contact the selected gene donors based on the selection criteria by sending them
a written invitation to participate in the study. In the invitation, the gene donors will be
informed that the trial relates to personalized prevention of CVD and requires that the
donor's health status parameters be assessed by a healthcare professional. The invitation
will not contain any references to the extent of the individual's genetic risk. The initial
consent will be sought for learning the polygenic risk score (PRS), for reporting the PRS to
the subject's family physician, and for participating in the trial. Such consent ensures that
the subjects are sufficiently informed to be able to participate in the study, while certain
details of the trial, including the genetic risk, will only be disclosed to the subjects
later by their family physician.
After having obtained the initial consent from the subjects the high-PRS subjects will be
randomized and the low-PRS subjects matched to the intervention group. The EGC will
thereafter transmit the study subjects' data (names, ID-s) to the family physicians. The PRS
data will be extended for the intervention group subjects only. The PRS-s for controls will
be extended at the end of the follow-up period. The family physicians will contact the
subjects and schedule the first visit, during which they will present detailed information
about the trial and obtain informed consent from participants. Blinding the controls will
ensure that any changes in health behavior during the trial are not connected to the high
PRS. At the end of the trial, the controls will be informed of their genetic risk and
provided counseling and treatment similar to that for the intervention group at the first
visit.
Sampling and power calculation
The sampling frame for the trial will consist of all of the EGC's gene donors (202,282
individuals as of 1 January 2022). The target group will be selected from the EGC's database
from among gene donors who are not suffering from CVD or diabetes, based on their PRS, BMI,
and age. The sample will consist of surviving males and females aged 25-44 who are overweight
(BMI 25-29.99), belong to the top or bottom quintile for polygenic risk for CVD,m, and have
not been diagnosed with CVD.
According to a preliminary query, the EGC's database contains data on about 2,000 individuals
with a high PRS for CVD (top quintile) and about 2,000 individuals with a low PRS for CVD
(bottom quintile) who are aged 25-44, have not been diagnosed with CVD and have a BMI of
25-29.99. 1300 of the approximately 2,000 individuals proven to belong to the highest
quintile for polygenic risk for CVD will be selected for the intervention group and first
control group of the trial, and approximately 650 of those in the lowest quintile for
polygenic risk for CVD will be selected for the second control group, with the assumption of
an average response rate of around 70% and a final number of subjects of up to 1,500 (500 in
the intervention group, 1,000 in the control groups). The investigators calculated that the
expected difference in the estimated 1-year BMI between the intervention (24 ±2.35) and
control (23.6) groups should be detectable with a type 1 error of 0.05 and 1-the power of
0.20 with the total sample of >1000 high polygenic risk men and women from the Biobank
database. To ensure the optimal number of physicians participating in the trial, the sampling
will also be based on the practice lists of family physicians and will be conducted utilizing
convenience sampling, by giving preference to practice lists that include larger numbers of
subjects. Some of the family physicians who will be participating in the trial have already
acted as partners to the EGC in the collection of the genetic data, which is also why their
practice lists will likely include more subjects. The sampling will proceed from practice
lists that include the greatest number of suitable gene donors to those with fewer potential
subjects until the required number of subjects has been achieved.
Randomization
Randomization will involve the intervention group and the first control group. Randomization
will be conducted at the EGC, as the family physicians will only be provided access to the
data of the individuals on their practice list and the randomization cannot be carried out at
their offices. The subjects in the second control group will be age- and sex-matched to the
intervention group.
Intervention
The intervention consists of three activities:
1. Informing the participant about the polygenic risk and calculating the total disease
risk. Only the intervention group participants will be informed about the high polygenic
risk.
2. Health counseling
3. Initiating preventive treatment of high blood pressure and/or high cholesterol. During a
visit, the family physician will announce the subject's polygenic risk for CVD (either
at the start or end of the trial, depending on the group) and discuss what it means,
calculate the subject's overall risk for CVD using the Kardiokompass tool, advise the
subject on weight loss and physical activity, and, if necessary, commence preventive
treatment. Between visits, a mobile application will be utilized to collect data about
the subjects' level of physical activity and body weight as well as to send reminders to
the subjects every two weeks regarding exercise and healthy lifestyle choices.
Treatment of subjects with high or moderate overall risk for CVD
Subjects with high or moderate overall risk will be advised on healthy lifestyle choices and,
where necessary, provided preventive treatment by their family physician. All subjects will
receive treatment according to the treatment guidelines of the European Society of Cardiology
(ESC) and their personal risk score. Although this treatment of patients conforms to modern
standard primary care practices, additional intervention guidelines will be drawn up in
Estonian for the trial.
