Genetic Testing and Motivational Counseling for FH

NCT04656028 | Active Not Recruiting

• 1 other identifier: 08-03/19
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

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

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

Outcome Measures

Primary Outcomes (5)

• 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)

  3 months

• 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)

  3 months

• 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

  3 months

• 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))

  3 months

• 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)

  3 months

Secondary Outcomes (5)

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

  15 months

• Change in the number of relatives who underwent cascade screening

  15 months

• Change in the proportion of people adhering to drug therapy

  15 months

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

  15 months

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

  15 months

Study Arms (4)

Group 1 - without genetic testing; subgroup without motivational counseling

ACTIVE COMPARATOR

Group 1 - without genetic testing; subgroup without motivational counseling

Diagnostic Test: Lipid analysis; Other: Consultation with a cardiologist-lipidologist (correction of therapy, lifestyle, diet); Other: Visit 1; Other: Visit 2; Other: Visit 3; Other: Visit 4

Group 1 - without genetic testing; subgroup with motivational counseling

EXPERIMENTAL

Group 1 - without genetic testing; subgroup with motivational counseling

Behavioral: Motivational Counseling; Diagnostic Test: Lipid analysis; Other: Consultation with a cardiologist-lipidologist (correction of therapy, lifestyle, diet); Other: Visit 1; Other: Visit 2; Other: Visit 3; Other: Visit 4

Group 2 - with genetic testing; subgroup without motivational counseling

EXPERIMENTAL

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

Genetic: Genetic Testing; Diagnostic Test: Lipid analysis; Other: Consultation with a cardiologist-lipidologist (correction of therapy, lifestyle, diet); Other: Visit 1; Other: Visit 2; Other: Visit 3; Other: Visit 4

Group 2 - with genetic testing; subgroup with motivational counseling

EXPERIMENTAL

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

Genetic: Genetic Testing; Behavioral: Motivational Counseling; Diagnostic Test: Lipid analysis; Other: Consultation with a cardiologist-lipidologist (correction of therapy, lifestyle, diet); Other: Visit 1; Other: Visit 2; Other: Visit 3; Other: Visit 4

Interventions

Genetic Testing GENETIC

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).

Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Motivational Counseling BEHAVIORAL

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.

Also known as: Motivational Interviewing

Group 1 - without genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling

Lipid analysis DIAGNOSTIC_TEST

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

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

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

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.

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Visit 1 OTHER

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.

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Visit 2 OTHER

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

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Visit 3 OTHER

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.

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Visit 4 OTHER

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.

Group 1 - without genetic testing; subgroup with motivational counseling; Group 1 - without genetic testing; subgroup without motivational counseling; Group 2 - with genetic testing; subgroup with motivational counseling; Group 2 - with genetic testing; subgroup without motivational counseling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Medical Research Center for Therapy and Preventive Medicine: lead
• Moscow State University of Medicine and Dentistry: collaborator

Study Sites (1)

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

Moscow, 101000, Russia

Location

Related Publications (1)

• Blokhina AV, Ershova AI, Kopylova OV, Limonova AS, Karamnova NS, Shvabskaya OB, Kiseleva AV, Derbeneva SA, Meshkov AN, Drapkina OM. [Actual nutrition in adults with familial hypercholesterolemia]. Vopr Pitan. 2023;92(4):49-58. doi: 10.33029/0042-8833-2023-92-4-49-58. Epub 2023 Jun 30. Russian.

  PMID: 37801454 DERIVED

MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hypercholesterolemia, Autosomal Dominant, 3; Hyperlipoproteinemia Type III; Hypercholesterolemia; Treatment Adherence and Compliance; Medication Adherence; Patient Compliance

Interventions

Genetic Testing; Motivational Interviewing; Referral and Consultation; Diet

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Health Behavior; Behavior; Patient Acceptance of Health Care

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Directive Counseling; Counseling; Mental Health Services; Behavioral Disciplines and Activities; Professional Practice; Organization and Administration; Health Services Administration; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Alexey Meshkov, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Alexandra Ershova, MD, PhD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 7, 2020
• Study Start: June 15, 2020
• Primary Completion: January 30, 2025
• Study Completion: March 30, 2025
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)