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

Primary Purpose

Hypercholesterolemia, Familial, Hypercholesterolemia, Familial, 1, Hypercholesterolemia, Familial, 2

Status

Recruiting

Phase

Not Applicable

Locations

Russian Federation

Study Type

Interventional

Intervention

Genetic Testing

Motivational Counseling

Lipid analysis

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

Visit 1

Visit 2

Visit 3

Visit 4

About this trial

This is an interventional treatment trial for Hypercholesterolemia, Familial focused on measuring Familial Hypercholesterolemia, FH, genetic testing, motivational counseling, motivational interviewing, cascade screening, adherence, compliance, 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, Therapeutic Adherence, Therapeutic Adherence and Compliance, Patient Adherence, Familial Hypercholesterolemia - Heterozygous, psychological counseling, Adherence, Patient, Adherence, Medication, Treatment Adherence, Medication Adherence, Treatment Adherence and Compliance, Patient Compliance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of RussiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Group 1 - without genetic testing; subgroup without motivational counseling

Group 1 - without genetic testing; subgroup with motivational counseling

Group 2 - with genetic testing; subgroup without motivational counseling

Group 2 - with genetic testing; subgroup with motivational counseling

Arm Description

Group 1 - without genetic testing; subgroup without motivational counseling

Group 1 - without genetic testing; subgroup with motivational counseling

Group 2 - genetic testing has been performed; subgroup without motivational counseling.

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

Outcomes

Primary Outcome Measures

Change in the proportion of people who have reached the target level of LDL-Cholesterol

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)

Change in the number of relatives who underwent cascade screening

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)

Change in the proportion of people adhering to drug therapy

Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5

Change in the proportion of people adhering to the recommended physical activity

Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))

Change in the proportion of individuals adhering to the recommended dietary recommendations

Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)

Secondary Outcome Measures

Change in the proportion of people who have reached the target level of LDL-Cholesterol

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)

Change in the number of relatives who underwent cascade screening

Change in the proportion of people adhering to drug therapy

Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5

Change in the proportion of people adhering to the recommended physical activity

Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))

Change in the proportion of individuals adhering to the recommended dietary recommendations

Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)

Full Information

NCT ID

NCT04656028

First Posted

November 30, 2020

Last Updated

March 28, 2023

Sponsor

National Medical Research Center for Therapy and Preventive Medicine

Collaborators

Moscow State University of Medicine and Dentistry

1. Study Identification

Unique Protocol Identification Number

NCT04656028

Brief Title

Genetic Testing and Motivational Counseling for FH

Acronym

GENMOTIV-FH

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 15, 2020 (Actual)

Primary Completion Date

July 31, 2023 (Anticipated)

Study Completion Date

May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Medical Research Center for Therapy and Preventive Medicine

Collaborators

Moscow State University of Medicine and Dentistry

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

There are several tasks of the study: 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. To assess the impact of knowledge of patients with FH about the result of their FH genetic testing on the effectiveness of cascade screening. To assess the influence of motivational counseling of patients with FH on the adherence to a healthy lifestyle and hypolipidemic therapy. To assess the impact of motivational counseling of patients with FH on the effectiveness of cascade screening.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Familial Hypercholesterolemia, FH, genetic testing, motivational counseling, motivational interviewing, cascade screening, adherence, compliance, 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, Therapeutic Adherence, Therapeutic Adherence and Compliance, Patient Adherence, Familial Hypercholesterolemia - Heterozygous, psychological counseling, Adherence, Patient, Adherence, Medication, Treatment Adherence, Medication Adherence, Treatment Adherence and Compliance, Patient Compliance

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

The trial is a randomized prospective cohort study. The study will include patients 18 years of age and older with a probable or definite diagnosis of FH according to the Dutch criteria (6 points or more). A total of 180 patients will be included in the study. All patients will be randomly divided into 2 groups for genetic testing. Randomization will be performed as block randomization with a 2:1 allocation ratio (2 with genetic testing : 1 without genetic testing). The allocation ratio 2:1 was chosen because in the group with genetic testing there will be cases where mutation(s) associated with FH will be identified and cases where the mutation(s) will not be identified. A separate analysis is planned in patients with genetic testing and identified mutation(s) and in patients with genetic testing but no identified mutation(s). Each study group will be randomized into 2 subgroups depending on the conduct of motivational counseling with an 1:1 allocation ratio.

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group 1 - without genetic testing; subgroup without motivational counseling

Arm Type

Active Comparator

Arm Description

Group 1 - without genetic testing; subgroup without motivational counseling

Arm Title

Group 1 - without genetic testing; subgroup with motivational counseling

Arm Type

Experimental

Arm Description

Group 1 - without genetic testing; subgroup with motivational counseling

Arm Title

Group 2 - with genetic testing; subgroup without motivational counseling

Arm Type

Experimental

Arm Description

Group 2 - genetic testing has been performed; subgroup without motivational counseling.

Arm Title

Group 2 - with genetic testing; subgroup with motivational counseling

Arm Type

Experimental

Arm Description

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

Intervention Type

Genetic

Intervention Name(s)

Genetic Testing

Intervention Description

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).

Intervention Type

Behavioral

Intervention Name(s)

Motivational Counseling

Other Intervention Name(s)

Motivational Interviewing

Intervention Description

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: Increasing motivation for a healthy lifestyle; Increasing adherence to treatment; 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.

Intervention Type

Diagnostic Test

Intervention Name(s)

Lipid analysis

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

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

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Visit 1

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Visit 2

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Visit 3

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Visit 4

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in the proportion of people who have reached the target level of LDL-Cholesterol

Description

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)

Time Frame

3 months

Title

Change in the number of relatives who underwent cascade screening

Description

Time Frame

3 months

Title

Change in the proportion of people adhering to drug therapy

Description

Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5

Time Frame

3 months

Title

Change in the proportion of people adhering to the recommended physical activity

Description

Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))

Time Frame

3 months

Title

Change in the proportion of individuals adhering to the recommended dietary recommendations

Description

Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Change in the proportion of people who have reached the target level of LDL-Cholesterol

Description

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)

Time Frame

15 months

Title

Change in the number of relatives who underwent cascade screening

Description

Time Frame

15 months

Title

Change in the proportion of people adhering to drug therapy

Description

Change in the proportion of people adhering to drug therapy according to the questionnaire MARS-5

Time Frame

15 months

Title

Change in the proportion of people adhering to the recommended physical activity

Description

Change in the proportion of people adhering to the recommended physical activity (according to the Global Physical Activity Questionnaire (GPAQ))

Time Frame

15 months

Title

Change in the proportion of individuals adhering to the recommended dietary recommendations

Description

Change in the proportion of individuals adhering to the recommended dietary recommendations (according to 24-hour Dietary Recall and Food Frequency Questionnaires)

Time Frame

15 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alexandra Ershova, MD, PhD

Phone

+79165598536

alersh@mail.ru

First Name & Middle Initial & Last Name or Official Title & Degree

Alexey Meshkov, MD, PhD

Phone

+79015121271

meshkov@lipidclinic.ru

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexey Meshkov, MD, PhD

Organizational Affiliation

National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alexandra Ershova, MD, PhD

Organizational Affiliation

National Medical Research Centre for Therapy and Preventive Medicine, Ministry of Health of Russia

Official's Role

Study Director

Facility Information:

Facility Name

National Medical Research Centre for Therapy and Preventive Medicine of the Ministry of Health of Russia

City

Moscow

ZIP/Postal Code

101000

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alexandra Ershova, MD, PhD

Phone

+79165598536

alersh@mail.ru

First Name & Middle Initial & Last Name & Degree

Alexey Meshkov, MD, PhD

Phone

+79015121271

meshkov@lipidclinic.ru

First Name & Middle Initial & Last Name & Degree

Alexey Meshkov, MD, PhD

First Name & Middle Initial & Last Name & Degree

Alexandra Ershova, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

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Genetic Testing and Motivational Counseling for FH

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