Genetic Testing and Motivational Counseling for FH (GENMOTIV-FH)

November 8, 2023 updated by: National Medical Research Center for Therapy and Preventive Medicine

Impact of Genetic Testing and Motivational Counseling on the Adherence to Healthy Lifestyle and Hypolipidemic Therapy and Efficiency of Cascade Screening in Patients With Familial Hypercholesterolemia (GENMOTIV-FH)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

There are several tasks of the study:

  1. To assess the effect of knowledge of patients with FH about the result of their FH genetic testing on the adherence to a healthy lifestyle and hypolipidemic therapy.
  2. To assess the impact of knowledge of patients with FH about the result of their FH genetic testing on the effectiveness of cascade screening.
  3. To assess the influence of motivational counseling of patients with FH on the adherence to a healthy lifestyle and hypolipidemic therapy.
  4. To assess the impact of motivational counseling of patients with FH on the effectiveness of cascade screening.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Alexandra Ershova, MD, PhD
  • Phone Number: +79165598536
  • Email: alersh@mail.ru

Study Contact Backup

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 101000
        • Recruiting
        • National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia
        • Contact:
          • Alexandra Ershova, MD, PhD
          • Phone Number: +79165598536
          • Email: alersh@mail.ru
        • Sub-Investigator:
          • Alexandra Ershova, MD, PhD
        • Contact:
        • Principal Investigator:
          • Alexey Meshkov, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Probable or definite diagnosis of FH according to the Dutch criteria (6 points or more);
  • Signed informed consent;

Exclusion Criteria:

  • Pregnancy or lactation at the time of enrollment
  • Established active severe infectious disease or severe hematologic, metabolic, gastrointestinal or endocrine dysfunctions (for example, uncontrolled thyroid dysfunction or uncontrolled diabetes mellitus) in the opinion of the investigator
  • Active liver disease
  • Estimated GFR≤ 30 ml / min / 1.73m2
  • Any other conditions at Visit 1 that, according to the investigator's opinion, render the patient ineligible for inclusion in the study, may interfere with the patient's participation in the study or patient's completion of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1 - without genetic testing; subgroup without motivational 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.
Experimental: Group 1 - without genetic testing; subgroup with motivational 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.

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.
Other Names:
  • Motivational Interviewing
Experimental: Group 2 - with genetic testing; subgroup without motivational counseling
Group 2 - genetic testing has been performed; subgroup without motivational 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.

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).
Experimental: Group 2 - with genetic testing; subgroup with motivational counseling
Group 2 - genetic testing has been performed; subgroup with motivational 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.

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.
Other Names:
  • Motivational Interviewing
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the proportion of people who have reached the target level of LDL-Cholesterol
Time Frame: 3 months
Change in the proportion of people who have reached the target level of LDL-Cholesterol (target values of LDL-C according to the ESC Dislipidaemia Guidelines 2019)
3 months
Change in the number of relatives who underwent cascade screening
Time Frame: 3 months
Change in the number of relatives who underwent cascade screening (% of relatives out of all available relatives. Available relatives are those who are alive and live in the region of where the study is conducted (Moscow and Moscow region)
3 months
Change in the proportion of people adhering to drug therapy
Time Frame: 3 months
Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5
3 months
Change in the proportion of people adhering to the recommended physical activity
Time Frame: 3 months
Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))
3 months
Change in the proportion of individuals adhering to the recommended dietary recommendations
Time Frame: 3 months
Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the proportion of people who have reached the target level of LDL-Cholesterol
Time Frame: 15 months
Change in the proportion of people who have reached the target level of LDL-Cholesterol (target values of LDL-C according to the ESC Dislipidaemia Guidelines 2019)
15 months
Change in the number of relatives who underwent cascade screening
Time Frame: 15 months
Change in the number of relatives who underwent cascade screening (% of relatives out of all available relatives. Available relatives are those who are alive and live in the region of where the study is conducted (Moscow and Moscow region)
15 months
Change in the proportion of people adhering to drug therapy
Time Frame: 15 months
Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5
15 months
Change in the proportion of people adhering to the recommended physical activity
Time Frame: 15 months
Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))
15 months
Change in the proportion of individuals adhering to the recommended dietary recommendations
Time Frame: 15 months
Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)
15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Medical Research Center for Therapy and Preventive Medicine

Collaborators

Moscow State University of Medicine and Dentistry

Investigators

  • Principal Investigator: Alexey Meshkov, MD, PhD, National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia
  • Study Director: Alexandra Ershova, MD, PhD, National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2020

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

March 30, 2025

Study Registration Dates

First Submitted

November 30, 2020

First Submitted That Met QC Criteria

November 30, 2020

First Posted (Actual)

December 7, 2020

Study Record Updates

Last Update Posted (Actual)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 8, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-03/19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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