Health for Hungary (H4H) - Longitudinal Collection of Blood Samples and Corresponding Data

BACKGROUND

The H4H study monitors health changes for 10 years in participants who are healthy at the outset but are at risk to develop new-onset health conditions. It uses a prospective study design and encompasses over 100,000 person-years of follow-up, allowing close observation of disease trajectories in relation to risk factors and medication use. This provides a unique opportunity to collect data on current tendencies in non-communicable disease (NCD) presentation and management.

Major NCDs (i.e., cardiovascular disease, cancer, type 2 diabetes and chronic respiratory disease) cause a significant loss in quality of life and are responsible for over 90 percent of Hungary's all-cause mortality. Therefore, there is growing demand for screening tools that might be used at minimal expense to reduce the overall burden of diseases. 'Early diagnosis' and recognition of high-risk states prior to the development of overt clinical diseases would allow better therapeutic outcomes and help preserve quality of life longer in the society.

Blood tests are valuable screening tools for many conditions and may be used for population health monitoring. Better understanding of blood composition, along with establishing reference ranges for blood constituents, is essential for developing effective blood-based health monitoring strategies.

High-information-content detection methods, including molecular fingerprinting, proteomics and metabolomics are expected to promote the discovery of novel disease biomarkers. By assessing a wide range of molecules, multiple disease-specific variables may be recognized.

Apart from multimodal analysis of blood samples, aliquots of all samples are preserved in a dedicated biobank with a commitment to accommodate a comprehensive collection of biospecimens for decades and to facilitate long-term research arrangements with the intention to accelerate future discoveries.

OBJECTIVES

The study aims to address the following objectives:

A) Establish reference ranges for infrared molecular fingerprinting and other high-information-content analysis methods (i.e., proteomics and metabolomics) in a non-symptomatic population using a cross-sectional approach.

B) Define characteristics of healthy aging and establish personalized reference intervals for infrared molecular fingerprinting and other high-information-content analysis methods using a longitudinal approach.

C) Identify novel biomarkers for non-communicable diseases, including coronary artery disease, lung cancer and diabetes, using infrared molecular fingerprinting and other high-information-content analysis on blood samples.

D) Identify novel blood-based risk factors for non-communicable diseases and discover indicators of precursor diseases using infrared molecular fingerprinting and other high-information-content analysis methods.

The findings of the current study will be instrumental in identifying disease specific deviations of human blood composition. This could lead to the discovery of 'novel biomarkers'.

Overall, the study will determine whether the molecular composition of human plasma remains stable over time and will test whether deeper analysis of blood samples can form the basis of population health monitoring.

STUDY DESIGN

The project is conducted in a single-country, multicenter, prospective, longitudinal format. Sample collection is scheduled for ten years according to this protocol.

PARTICIPANTS

The study enrolls healthy subjects of > 40 years or > 50 years in low- or high-risk cohorts, respectively, who are followed up for ten years. Enrollment continues until 15,000 subjects are enrolled.

PROCEDURES:

Blood sample collection occurs in accordance with the clinical routine and plasma samples are processed for high-information-content analysis. Additional blood tubes are submitted to clinical laboratory testing. Health data collection utilizes self-report questionnaires and review of medical records.

In the high-risk cohort, a comprehensive medical examination is performed after the first 4 blood samples are collected, including screening tests for lung cancer and coronary artery disease, i.e., a low-dose CT scan of the chest and coronary artery calcium score test (heart scan). These investigations are repeated after a follow-up period of 5 years.

WITHDRAWAL OF CONSENT, DISCONTINUATION FROM THE STUDY

Participation in this sample and data collection project is voluntary, and each participant has the right to withdraw their consent at any time without any consequence concerning possible future treatment or future blood donations.

Low- and Moderate-risk Cohort:

Inclusion criteria

• Signed informed consent form (ICF) of the study.
• Age > 40 years.
• Willingness to fill in the study questionnaire.
• No clinically relevant symptoms as assessed by the investigator, subjects with existing medical conditions may be eligible given that they are symptom free and that full treatment of the condition is medically confirmed.
• Willingness to participate in future visits.

Exclusion criteria

• Self-reported pregnancy (no test).
• Indications of clinically relevant medical conditions in self-reported healthy subjects.
• Self-reported symptom-free HIV, HCV and HBV infections. If HIV, HBV or HCV serology test is done and any of them are positive, the subject will be considered a screen failure.
• Any conditions preventing blood-draw.
• Vulnerable subjects.
• Foreseeable lack of compliance.
• Participation in another sample collection project of the same sponsor, in order to avoid double evaluation of the same subject.
• Participation (currently or in the past month) in an early phase clinical trial (phases I and II) involving testing of pharmaceutical products, if the last dose of pharmaceutical product administration was within 30 days of the first sample collection, and / or further pharmaceutical product administration is planned.
• Vaccination within the last 14 days.

High-risk Cohort:

Inclusion criteria

• Signed informed consent form (ICF) of the study.
• Age > 50 years.
• Willingness to fill in the study questionnaire.
• Willingness to participate in future visits and medical investigations, the presence of at least 2 of the following 3 risk factors (inclusion criteria #5-7):
• Hypertension, receiving antihypertensive treatment.
• Dyslipidemia/ Hypercholesterolemia (>5.2mmol/L total cholesterol level), on or not on statin-treatment.
• Active or former smoker, with smoking history of at least 20 pack-years, and/or the presence of intermediate lung nodule on prior LDCT testing.
• No clinically relevant symptoms as assessed by the investigator; subjects with existing medical conditions may be eligible given that they are symptom free and that treatment of the condition is well documented.

Exclusion criteria

• Self-reported pregnancy (no test).
• Cardiovascular disease (including obstructive coronary artery disease, peripheral artery disease, aortic aneurysm) or other clinically significant heart disease (congenital, valvular heart disease, cardiomyopathy, heart failure and heart disease requiring ICD [implantable cardioverter defibrillator] or pacemaker therapy).
• Interstitial lung disease or severe COPD (chronic obstructive pulmonary disease) in GOLD stages 3 or 4.
• Active cancer or malignant disease with less than 5 years history of remission.
• Indications of clinically relevant medical conditions in self-reported healthy subjects, especially if (a) the condition requires regular or constant specialist checkups, or (b) pharmacological therapy indicates the presence of significant NCDs or multimorbidity, i.e., chronic polypharmacy (use of 5 or more medications at enrollment or over the last 6 months), or drug therapy necessitating a specialist input for initiation or management (e.g., combined anti-diabetic treatment with two or more medications).
• Self-reported symptom-free HIV, HCV and HBV infections. If HIV, HBV or HCV serology test is done and any of them are positive, the subject will be considered a screen failure.
• Any conditions preventing blood-draw or CT scans.
• Vulnerable subjects.
• Foreseeable lack of compliance.
• Participation in another sample collection project of the same sponsor, in order to avoid double evaluation of the same subject. 'High-risk' subjects enrolled in the low- and moderate-risk arm of the H4H study might be reallocated to the high-risk study arm after the first 4-5 visits.
• Participation (currently or in the past month) in an early phase clinical trial (phases I and II) involving testing of pharmaceutical products, if the last dose of pharmaceutical product administration was within 30 days of the first sample collection, and/or further pharmaceutical product administration is planned.
• Vaccination within the last 14 days of sample collection.