Associations of Combinations of Single-nucleotide Polymorphisms in Women With Premature Ovarian Failure

Cardiovascular Diseases Clinical Trial

Official title:

Associations of Combinations of Single-nucleotide Polymorphisms and Behavioural Risk Factors With Non-communicable Diseases and Adverse Outcomes in Women With Premature Ovarian Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04943354
• Other study ID #: 20-315-90017
• Status: Completed
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: December 12, 2023

Study information

• Verified date: July 2022
• Source: Ryazan State Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Research objective.

• To study the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with non-communicable diseases and adverse outcomes in women with premature ovarian failure.

Research objectives:

• To study the associations between combinations of single-nucleotide polymorphisms and behavioural risk factors with heart rate disorders and adverse outcomes in women with premature ovarian failure

• Examine the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with stable STIs in women with premature ovarian failure.

• Examine the associations between combinations of single nucleotide polymorphisms and behavioural risk factors with thrombomolia in women with premature ovarian failure

• Study the associations between combinations of single nucleotide polymorphisms and behavioural risk factors and adverse cardiovascular outcomes in women with premature ovarian failure.

Description:

Methods of research:

• Questionnaire .

• Clinical examination

• Blood levels of sex hormones

• Blood lipid spectrum

• Coagulogram

• Glycemic profile

• EchoCG

• SMAD

• ECG

• Daily ECG monitoring

• Questionnaire EQ-5D

• Single-nucleotide polymorphisms of genes of the reninangyotensin-aldosterone system group (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), pro-inflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) polymorphisms.

Subject of study.

Women under 45 with Premature Ovarian Failure (PED). It is planned to include 615 people in the study. The study will have both prospective and retrospective parts. Patients will be divided into 4 groups:

• Women with OED without cardiovascular disease

• Women with OAI who have cardiovascular disease

• Control group No 1 Women with normal ovarian function without cardiovascular disease.

• Control group 2 Women with normal ovarian function without cardiovascular disease.

The groups will be comparable in number. All data obtained will be calculated for each group separately. A comparative analysis will then be made for all four groups.

Traditional risk factors, existing non-communicable diseases and the quality of life of patients will be identified using standard research methods.

The selected polymorphism groups are associated with various pathological processes leading to unfavourable cardiovascular outcomes. Their role has not been assessed in patients with premature ovarian failure.

The power of the study was calculated based on the expected number of adverse outcomes.

The division of patients into groups is related to the need to compare and evaluate unfavourable outcomes and non-communicable diseases in patients in order to create a risk scale.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: December 12, 2023
• Est. primary completion date: June 3, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A to 45 Years

Eligibility

Inclusion Criteria:

• women under 45 years old

• presence of premature ovarian insufficiency in the medical history

Exclusion Criteria:

• male gender

• age over 45 years

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiovascular Diseases
• Coronary Disease
• Embolism
• Menopause, Premature
• Polymorphism, Single Nucleotide
• Premature Birth
• Primary Ovarian Insufficiency
• Pulmonary Embolism

Intervention

Behavioral:
• Taking a person's venous blood
Collection of 5 ml of the patient's venous blood, carried out according to standard rules.

Locations

Country	Name	City	State
Russian Federation	Sergey Vladimirovich Lopukhov	Ryazan	Ryazan Region

Sponsors (1)

Lead Sponsor	Collaborator
Ryazan State Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pregnancy (number)	Number of pregnancies in history	2 year
Other	Childbirth (number)	Number of pregnancies that ended in childbirth	2 year
Other	Menopause (yes/no)	Current presence or absence of menopause	2 year
Other	Surgical removal of both ovaries (yes/no)	History of surgery involving bilateral removal of both ovaries	2 year
Other	Presence of amenorrhoea (at least 4 months) (yes/no)	A history of amenorrhoea for at least 4 months	2 year
Other	Follicle stimulating hormone (FSH) level (mMed/ml)	Blood follicle-stimulating hormone content expressed in mMED/ml	2 year
Other	Age at menopause (years)	Age of onset of menopause	2 year
Other	Length of post-menopause (years)	How many years a person has been in the post-menopausal phase	2 year
Other	Taking oral contraceptives (yes/no)	Whether the patient is continuously taking oral contraceptives	2 year
Other	Taking hormone replacement therapy (HRT) (yes/no)	Whether the patient is taking regular hormone replacement therapy	2 year
Other	Length of time on hormone replacement therapy (years)	How long the patient has been on hormone replacement therapy	2 year
Other	Smoking status (yes/no)	Does the patient use nicotine-containing substances on a regular basis	2 year
Other	Number of cigarettes smoked per day (number)	How many cigarettes the patient smokes per day on average	2 year
Other	Smoking experience (years)	Number of years of active nicotine use by the patient	2 year
Other	Smoking index (points)	Calculated as the number of cigarettes smoked per day and years of smoking experience divided by 20.	2 year
Other	Height (cm)	Patient's height measured in centimetres	2 year
Other	Weight (kg)	Patient weight measured in kilograms	2 year
Other	BMI (kg/m2)	Body mass index is determined using the standard method	2 year
Other	Waist circumference (cm)	Waist circumference measured in centimetres using the standard method	2 year
Other	Hip circumference (cm)	Hip circumference measured in centimetres using the standard method	2 year
Other	Waist circumference to hip circumference ratio (WHR) (number)	Waist circumference to hip circumference index calculated using the standard method	2 year
Other	Secondary education (yes/no)	Does the patient have a high school education	2 year
Other	Secondary vocational education (yes/no)	Does the patient have a secondary vocational education	2 year
Other	Higher education (yes/no)	Does the patient have a university degree	2 year
Other	Systolic blood pressure (mmHg)	Systolic blood pressure measured using the standard method	2 year
Other	Diastolic blood pressure (mmHg)	Diastolic blood pressure measured using the standard method	2 year
Other	Heart rate (number)	Heart rate measured using the standard method	2 year
Other	Radial artery pulse (beats per minute).	Radial artery pulse measured using standard methods	2 year
Other	Arterial hypertension (yes/no)	History of arterial hypertension	2 year
Other	Ultrasound examination of the heart	Ultrasound examination of the heart carried out using standard methods to detect cardiac abnormalities	2 year
Other	Total cholesterol (mmol/l)	Total cholesterol measured by standard methods	2 year
Other	High-density lipoproteins (HDL) (mmol/l)	High-density lipoproteins measured by standard methods	2 year
Other	Low density lipoproteins LDL (mmol/l)	Low density lipoproteins measured by standard methods	2 year
Other	Triglycerides (mmol/l)	Triglycerides measured by standard methods	2 year
Other	Cholesterol/HDL ratio (number)	Calculated using the standard method	2 year
Other	Blood glucose level (mmol/l)	Amount of glucose in the blood measured by the standard method	2 year
Other	Glycated haemoglobin (HbA1c), (percent %)	Glycated haemoglobin measured by standard methods	2 year
Other	Diabetes mellitus (yes/no)	Indication of diabetes mellitus in the patient's medical history	2 year
Other	Taking antihypertensive medication (yes/no)	Indication of antihypertensive medication in the patient's medical history	2 year
Other	Taking hypolipidemic medicines (yes/no)	Use of hypolipidemic drugs in a patient's history	2 year
Other	Metabolic syndrome (yes/no)	Indicating a history of metabolic syndrome	2 year
Other	Presence of post-menopausal diagnosis: arrhythmia or other rhythm disturbances (yes/no)	Post-menopausal diagnosis of arrhythmia or other rhythm disturbances based on medical history	2 year
Other	Presence of a post-menopausal diagnosis of coronary heart disease (yes/no)	Presence of post-menopausal diagnosis of coronary heart disease according to medical history	2 year
Other	Presence of a post-menopausal diagnosis of myocardial infarction (yes/no)	Post-menopausal diagnosis of myocardial infarction based on medical history	2 year
Other	Presence of post-menopausal diagnosis: thromboembolism (yes/no)	Post-menopausal diagnosis of thromboembolism based on medical history	2 year
Other	Post-menopausal diagnosis of varicose veins in the lower limbs (yes/no)	Post-menopausal diagnosis of varicose veins in the lower limbs based on medical history	2 year
Other	Presence of a post-menopausal diagnosis: Acute cerebral haemorrhage (yes/no)	Post-menopausal diagnosis of acute cerebral haemorrhage on medical history	2 year
Other	Deaths from cardiovascular disease in the post-menopausal period (yes/no)	Cardiovascular deaths in the post-menopausal period based on the pathologist's medical history report	2 year
Other	A history of cancer (yes/no)	Determined on the basis of the medical history	2 year
Other	AGT gene Met235Thr, rs699 polymorphism	Identification of Met235Thr/rs699 polymorphisms in the AGT gene	2 year
Other	ACE gene Alu Ins/Del I>D, rs4646994 polymorphism	Identification of Alu Ins/Del I>D, rs4646994 polymorphisms in the ACE gene	2 year
Other	NOS3 gene C786T, rs2070744 polymorphism	Identification of C786T, rs2070744 polymorphisms in the NOS3 gene	2 year
Other	EDN1 gene Lys198Asn, rs5370 polymorphism	Identification of Lys198Asn, rs5370 polymorphisms in the EDN1 gene	2 year
Other	ITGB3 gene Leu33Pro, rs5918 polymorphism	Identification of Leu33Pro, rs5918 polymorphisms in the ITGB3 gene	2 year
Other	ITGA2 gene C807T, rs1126643 polymorphism	Identification of C807T, rs1126643 polymorphisms in the ITGA2 gene	2 year
Other	FGB gene 455G-A, rs1800790 polymorphism	Identification of 455G-A, rs1800790 polymorphisms in the FGB gene	2 year
Other	SERPINE (PAI) 1 gene 675 5G/4G, rs1799768 polymorphism	Identification of 675 5G/4G, rs1799768 polymorphisms in the SERPINE (PAI) 1 gene	2 year
Other	CRP gene C3872T, rs1205 polymorphism	Identification of C3872T, rs1205 polymorphisms in the CRP gene	2 year
Other	IL17A gene G-197A, rs2275913 polymorphism	Identification of G-197A, rs2275913 polymorphisms in the IL17A gene	2 year
Other	IL2 gene T-330G, rs2069762 polymorphism	Identification of T-330G, rs2069762 polymorphisms in the IL2 gene	2 year
Other	IL10 gene C-592A, rs1800872 polymorphism	Identification of C-592A, rs1800872 polymorphisms in the IL10 gene	2 year
Other	TNF gene G-308A, rs1800629 polymorphism	Identification of G-308A, rs1800629 polymorphisms in the TNF gene	2 year
Other	CRP gene A-717G, rs2794521 polymorphism	Identification of A-717G, rs2794521 polymorphisms in the CRP gene	2 year
Other	IL6 gene C-174G, rs1800795 polymorphism	Identification of C-174G, rs1800795 polymorphisms in the IL6 gene	2 year
Other	TLR2 gene Arg753Gln, rs5743708 polymorphism	Identification of Arg753Gln, rs5743708 polymorphisms in the TLR2 gene	2 year
Other	TLR3 gene Phe412Leu, rs3775291 polymorphism	Identification of Phe412Leu, rs3775291 polymorphisms in the TLR3 gene	2 year
Other	TLR4 gene Asp299Gly, rs4986790 polymorphism	Identification of Asp299Gly, rs4986790 polymorphisms in the TLR4 gene	2 year
Other	TLR6 gene Ser249Pro, rs5743810 polymorphism	Identification of Ser249Pro, rs5743810 polymorphisms in the TLR6 gene	2 year
Other	TLR9 gene T-1237C, rs5743836 polymorphism	Identification of T-1237C, rs5743836 polymorphisms in the TLR9 gene	2 year
Primary	Age (years)	Patient age in years	2 year
Secondary	Menarche (years)	Age of onset of menarche expressed in years	2 year