Genetic Testing and Motivational Counseling for FH

Summary

To date, there are highly effective lipid-lowering drugs, the combination of which makes it possible to achieve the target level of LDL-C in most patients with familial hypercholesterolemia (FH). However, the effectiveness of treatment of FH patients strongly depends on adherence to lipid-lowering therapy and to the healthy lifestyle, as well as the detection of the disease and the therapy prescription as early as possible, better in childhood. The aim of the study is to assess the impact of genetic testing and motivational counseling on the effectiveness of treatment and cascade screening in patients with FH.

Conditions

• Hypercholesterolemia, Familial
• Hypercholesterolemia, Familial, 1
• Hypercholesterolemia, Familial, 2
• Hypercholesterolemia, Familial, 3
• Hypercholesterolemia, Familial, 4
• Hypercholesterolemia, Familial, 4, Autosomal Recessive
• Familial Hypercholesterolemia With Hyperlipemia
• Hypercholesterolemia, Autosomal Dominant, Type B
• Hypercholesterolemia, Autosomal Dominant
• Hypercholesterolemia, Autosomal Dominant, 3
• Apolipoprotein B-100, Familial Defective
• Genetic Testing
• Motivational Interviewing
• Therapeutic Adherence
• Therapeutic Adherence and Compliance
• Treatment Adherence
• Medication Adherence
• Treatment Adherence and Compliance
• Patient Adherence
• Compliance
• Patient Compliance
• Familial Hypercholesterolemia
• Familial Hypercholesterolemia - Heterozygous
• Adherence, Patient
• Adherence, Medication
• Adherence

Interventions

GENETIC

Genetic Testing

DNA is extracted using the QIAamp® DNA Blood Mini Kit (Qiagen, Germany). The DNA concentration is measured on a Qubit 4.0 fluorometer (Thermo Fisher Scientific, USA (TFS)). NGS is performed on Nextseq 550 (Illumina, San Diego, CA, USA). The library preparation is performed using the SeqCap EZ Prime Choice Library kit (Roche, Basel, Switzerland). The Roche panel is used, consisting of 244 (CDS + 25 bp padding) genes including LDLR, APOB, and PCSK9. Reads are aligned to the reference genome (GRCh37). Sequencing analysis resultes in fastq files. Data processing is performed with BWA, Picard, bcftools, GATK3 and generally followed the GATK best practices for variant calling. For clinical interpretation, genetic variants with frequencies in the gnomAD database \<0.5% are selected. The pathogenicity of variants is assessed according to the ACMG / AMP2015 guidelines. The identified SNPs are validated by Sanger sequencing (3500 DNA Analyzer, TFS).

BEHAVIORAL

Motivational Counseling

Motivational counseling will be carried out during Visit 2 and in one month after Visit 2 by certified psychologist with taking into account the results of the psychodiagnostic survey conducted at the first and second visits. The goals of motivational counseling: 1. Increasing motivation for a healthy lifestyle; 2. Increasing adherence to treatment; 3. Increased motivation to invite relatives for cascade screening. Motivational counseling will be carried out using methods of motivational interviewing, transtheoretical model of changes, cognitive-behavioral therapy, extended preventive counseling.

DIAGNOSTIC_TEST

Lipid analysis

Assessment of total cholesterol, low density lipoproteins, high density lipoproteins, triglycerides, alanine aminotransferase.

OTHER

Consultation with a cardiologist-lipidologist (correction of therapy, lifestyle, diet)

All patients will be prescribed ezetimibe and statins (atorvastatin / rosuvastatin) at the maximum dosage. If somebody has an intolerance to atorvastatin, the drug will be replaced with rosuvastatin and vice versa. In case of intolerance to all drugs from the statin group, the patient will be prescribed ezetimibe with a PCSK9 inhibitor (alirocumab / evolocumab). After receiving the results of the lipid spectrum, ALT, if necessary, the lipid-lowering therapy may be corrected.

OTHER

Visit 1

Visit 1: initially (on enrollment) - informed consents signing; lipid blood tests, patient data gathering, and consultation of cardiologist-lipidologist for optimization of lipid-lowering therapy and lifestyle; filling all questionnaires. After this visit patients are randomized to groups with or without genetic testing and then randomized to groups with or without motivational counseling. Each visit consists of two patient's attendances to the medical center. At the first attendance, it is planned to take blood for analysis, fill out questionnaires; at the second attendance - to perform, a consultation with a cardiologist-lipidologist according to the results of blood analysis. The time interval between two attendances is ≤ 7 days.

OTHER

Visit 2

Visit 2 (in 2-3 months): lipid blood tests, patient data gathering, and consultation of cardiologist-lipidologist for optimization of lipid lowering-therapy and lifestyle; filling all questionnaires. Patients from the group with genetic testing will get the result of this genetic testing. Patients from the group with motivational counseling will get two consultations with a psychologist (motivational counseling on lifestyle modification) during Visit 2 and in one month after Visit 2. Each visit consists of two patient's attendances to the medical center. At the first attendance, it is planned to take blood for analysis, fill out questionnaires; at the second attendance - to perform a consultation with a cardiologist-lipidologist according to the results of blood analysis. The time interval between two attendances is ≤ 7 days

OTHER

Visit 3

Visit 3 (in 3 months after Visit 2): lipid blood tests, patient data gathering, and consultation of cardiologist-lipidologist for optimization of lipid-lowering therapy and lifestyle; filling all questionnaires. Each visit consists of two patient's attendances to the medical center. At the first attendance, it is planned to take blood for analysis, fill out questionnaires; at the second attendance - to perform a consultation with a cardiologist-lipidologist according to the results of blood analysis. The time interval between two attendances is ≤ 7 days.

OTHER

Visit 4

Visit 4 (in 12 months after Visit 3): lipid blood tests, patient data gathering, and consultation of cardiologist-lipidologist for optimization of lipid-lowering therapy and lifestyle; filling all questionnaires. Each visit consists of two patient's attendances to the medical center. At the first attendance, it is planned to take blood for analysis, fill out questionnaires; at the second attendance - to perform a consultation with a cardiologist-lipidologist according to the results of blood analysis. The time interval between two attendances is ≤ 7 days.

Sponsors & Collaborators

• Moscow State University of Medicine and Dentistry

  collaborator OTHER

• National Medical Research Center for Therapy and Preventive Medicine

  lead OTHER_GOV

Principal Investigators

• Alexey Meshkov, MD, PhD · National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia

• Alexandra Ershova, MD, PhD · National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-06-15

Primary Completion

2025-01-30

Completion

2025-03-30

Countries

• Russia

Study Locations