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

Primary Purpose

Primary Ovarian Insufficiency, Cardiovascular Diseases, Menopause, Premature

Status
Active
Phase
Not Applicable
Locations
Russian Federation
Study Type
Interventional
Intervention
Taking a person's venous blood
Sponsored by
Ryazan State Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Primary Ovarian Insufficiency focused on measuring premature ovarian failure, hypoestrogenism, artificial menopause, cardiovascular disease, chronic non-infectious disease, cardiovascular outcomes, coronary heart disease, pulmonary embolism, cardiac arrhythmias, heart rhythm disturbances, single nucleotide polymorphisms

Eligibility Criteria

undefined - 45 Years (Child, Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • women under 45 years old
  • presence of premature ovarian insufficiency in the medical history

Exclusion Criteria:

  • male gender
  • age over 45 years

Sites / Locations

  • Sergey Vladimirovich Lopukhov

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Study of single-nucleotide polymorphisms in women diagnosed with premature ovarian failure

Study of single-nucleotide polymorphisms in a control group of healthy women

Arm Description

Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), proinflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) in the study group of women diagnosed with premature ovarian failure.

Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (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) in a control group of healthy women .

Outcomes

Primary Outcome Measures

Age (years)
Patient age in years

Secondary Outcome Measures

Menarche (years)
Age of onset of menarche expressed in years

Full Information

First Posted
November 27, 2020
Last Updated
August 3, 2022
Sponsor
Ryazan State Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04943354
Brief Title
Associations of Combinations of Single-nucleotide Polymorphisms in Women With Premature Ovarian Failure
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
June 3, 2022 (Actual)
Study Completion Date
December 12, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ryazan State Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Ovarian Insufficiency, Cardiovascular Diseases, Menopause, Premature, Coronary Disease, Pulmonary Embolism, Arrhythmias, Cardiac, Polymorphism, Single Nucleotide
Keywords
premature ovarian failure, hypoestrogenism, artificial menopause, cardiovascular disease, chronic non-infectious disease, cardiovascular outcomes, coronary heart disease, pulmonary embolism, cardiac arrhythmias, heart rhythm disturbances, single nucleotide polymorphisms

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Women diagnosed with premature ovarian failure were selected from different medical institutions in Ryazan and the Ryazan region, all information was communicated to them in a clear and understandable way and they also signed an informed voluntary consent. Premature ovarian failure - defined as the occurrence of secondary amenorrhoea ≥4 months at the age of under 45 years together with FSH levels above 40 IU/L. Inclusion criteria were: female gender, age at menopause < 45 years, onset of secondary amenorrhoea ≥ 4 months, FSH levels higher than 40 IU/l, or a previous diagnosis of premature ovarian failure. The control group was formed based on comparability criteria of gender, age and BMI to minimise the influence of phenotype on the results. The control group consisted of women without signs of PEN, so we aimed to compare the health status of these two different groups of women.
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
238 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study of single-nucleotide polymorphisms in women diagnosed with premature ovarian failure
Arm Type
Active Comparator
Arm Description
Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (AGT, ACE), endothelial dysfunction (NOS3, EDN1), thrombosis-associated (ITGB3, ITGA2, FGB, GPIBA, SERPINE PAI1), proinflammatory (CRP, IL17A, IL2, IL10 1, IL10 2, TNFα, CRP 4, IL6, TLR2, TLR3, TLR4, TLR6, TLR9) in the study group of women diagnosed with premature ovarian failure.
Arm Title
Study of single-nucleotide polymorphisms in a control group of healthy women
Arm Type
Active Comparator
Arm Description
Study of genes affecting single nucleotide polymorphisms: Reninangiotensin-aldosterone system (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) in a control group of healthy women .
Intervention Type
Behavioral
Intervention Name(s)
Taking a person's venous blood
Intervention Description
Collection of 5 ml of the patient's venous blood, carried out according to standard rules.
Primary Outcome Measure Information:
Title
Age (years)
Description
Patient age in years
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Menarche (years)
Description
Age of onset of menarche expressed in years
Time Frame
2 year
Other Pre-specified Outcome Measures:
Title
Pregnancy (number)
Description
Number of pregnancies in history
Time Frame
2 year
Title
Childbirth (number)
Description
Number of pregnancies that ended in childbirth
Time Frame
2 year
Title
Menopause (yes/no)
Description
Current presence or absence of menopause
Time Frame
2 year
Title
Surgical removal of both ovaries (yes/no)
Description
History of surgery involving bilateral removal of both ovaries
Time Frame
2 year
Title
Presence of amenorrhoea (at least 4 months) (yes/no)
Description
A history of amenorrhoea for at least 4 months
Time Frame
2 year
Title
Follicle stimulating hormone (FSH) level (mMed/ml)
Description
Blood follicle-stimulating hormone content expressed in mMED/ml
Time Frame
2 year
Title
Age at menopause (years)
Description
Age of onset of menopause
Time Frame
2 year
Title
Length of post-menopause (years)
Description
How many years a person has been in the post-menopausal phase
Time Frame
2 year
Title
Taking oral contraceptives (yes/no)
Description
Whether the patient is continuously taking oral contraceptives
Time Frame
2 year
Title
Taking hormone replacement therapy (HRT) (yes/no)
Description
Whether the patient is taking regular hormone replacement therapy
Time Frame
2 year
Title
Length of time on hormone replacement therapy (years)
Description
How long the patient has been on hormone replacement therapy
Time Frame
2 year
Title
Smoking status (yes/no)
Description
Does the patient use nicotine-containing substances on a regular basis
Time Frame
2 year
Title
Number of cigarettes smoked per day (number)
Description
How many cigarettes the patient smokes per day on average
Time Frame
2 year
Title
Smoking experience (years)
Description
Number of years of active nicotine use by the patient
Time Frame
2 year
Title
Smoking index (points)
Description
Calculated as the number of cigarettes smoked per day and years of smoking experience divided by 20.
Time Frame
2 year
Title
Height (cm)
Description
Patient's height measured in centimetres
Time Frame
2 year
Title
Weight (kg)
Description
Patient weight measured in kilograms
Time Frame
2 year
Title
BMI (kg/m2)
Description
Body mass index is determined using the standard method
Time Frame
2 year
Title
Waist circumference (cm)
Description
Waist circumference measured in centimetres using the standard method
Time Frame
2 year
Title
Hip circumference (cm)
Description
Hip circumference measured in centimetres using the standard method
Time Frame
2 year
Title
Waist circumference to hip circumference ratio (WHR) (number)
Description
Waist circumference to hip circumference index calculated using the standard method
Time Frame
2 year
Title
Secondary education (yes/no)
Description
Does the patient have a high school education
Time Frame
2 year
Title
Secondary vocational education (yes/no)
Description
Does the patient have a secondary vocational education
Time Frame
2 year
Title
Higher education (yes/no)
Description
Does the patient have a university degree
Time Frame
2 year
Title
Systolic blood pressure (mmHg)
Description
Systolic blood pressure measured using the standard method
Time Frame
2 year
Title
Diastolic blood pressure (mmHg)
Description
Diastolic blood pressure measured using the standard method
Time Frame
2 year
Title
Heart rate (number)
Description
Heart rate measured using the standard method
Time Frame
2 year
Title
Radial artery pulse (beats per minute).
Description
Radial artery pulse measured using standard methods
Time Frame
2 year
Title
Arterial hypertension (yes/no)
Description
History of arterial hypertension
Time Frame
2 year
Title
Ultrasound examination of the heart
Description
Ultrasound examination of the heart carried out using standard methods to detect cardiac abnormalities
Time Frame
2 year
Title
Total cholesterol (mmol/l)
Description
Total cholesterol measured by standard methods
Time Frame
2 year
Title
High-density lipoproteins (HDL) (mmol/l)
Description
High-density lipoproteins measured by standard methods
Time Frame
2 year
Title
Low density lipoproteins LDL (mmol/l)
Description
Low density lipoproteins measured by standard methods
Time Frame
2 year
Title
Triglycerides (mmol/l)
Description
Triglycerides measured by standard methods
Time Frame
2 year
Title
Cholesterol/HDL ratio (number)
Description
Calculated using the standard method
Time Frame
2 year
Title
Blood glucose level (mmol/l)
Description
Amount of glucose in the blood measured by the standard method
Time Frame
2 year
Title
Glycated haemoglobin (HbA1c), (percent %)
Description
Glycated haemoglobin measured by standard methods
Time Frame
2 year
Title
Diabetes mellitus (yes/no)
Description
Indication of diabetes mellitus in the patient's medical history
Time Frame
2 year
Title
Taking antihypertensive medication (yes/no)
Description
Indication of antihypertensive medication in the patient's medical history
Time Frame
2 year
Title
Taking hypolipidemic medicines (yes/no)
Description
Use of hypolipidemic drugs in a patient's history
Time Frame
2 year
Title
Metabolic syndrome (yes/no)
Description
Indicating a history of metabolic syndrome
Time Frame
2 year
Title
Presence of post-menopausal diagnosis: arrhythmia or other rhythm disturbances (yes/no)
Description
Post-menopausal diagnosis of arrhythmia or other rhythm disturbances based on medical history
Time Frame
2 year
Title
Presence of a post-menopausal diagnosis of coronary heart disease (yes/no)
Description
Presence of post-menopausal diagnosis of coronary heart disease according to medical history
Time Frame
2 year
Title
Presence of a post-menopausal diagnosis of myocardial infarction (yes/no)
Description
Post-menopausal diagnosis of myocardial infarction based on medical history
Time Frame
2 year
Title
Presence of post-menopausal diagnosis: thromboembolism (yes/no)
Description
Post-menopausal diagnosis of thromboembolism based on medical history
Time Frame
2 year
Title
Post-menopausal diagnosis of varicose veins in the lower limbs (yes/no)
Description
Post-menopausal diagnosis of varicose veins in the lower limbs based on medical history
Time Frame
2 year
Title
Presence of a post-menopausal diagnosis: Acute cerebral haemorrhage (yes/no)
Description
Post-menopausal diagnosis of acute cerebral haemorrhage on medical history
Time Frame
2 year
Title
Deaths from cardiovascular disease in the post-menopausal period (yes/no)
Description
Cardiovascular deaths in the post-menopausal period based on the pathologist's medical history report
Time Frame
2 year
Title
A history of cancer (yes/no)
Description
Determined on the basis of the medical history
Time Frame
2 year
Title
AGT gene Met235Thr, rs699 polymorphism
Description
Identification of Met235Thr/rs699 polymorphisms in the AGT gene
Time Frame
2 year
Title
ACE gene Alu Ins/Del I>D, rs4646994 polymorphism
Description
Identification of Alu Ins/Del I>D, rs4646994 polymorphisms in the ACE gene
Time Frame
2 year
Title
NOS3 gene C786T, rs2070744 polymorphism
Description
Identification of C786T, rs2070744 polymorphisms in the NOS3 gene
Time Frame
2 year
Title
EDN1 gene Lys198Asn, rs5370 polymorphism
Description
Identification of Lys198Asn, rs5370 polymorphisms in the EDN1 gene
Time Frame
2 year
Title
ITGB3 gene Leu33Pro, rs5918 polymorphism
Description
Identification of Leu33Pro, rs5918 polymorphisms in the ITGB3 gene
Time Frame
2 year
Title
ITGA2 gene C807T, rs1126643 polymorphism
Description
Identification of C807T, rs1126643 polymorphisms in the ITGA2 gene
Time Frame
2 year
Title
FGB gene 455G-A, rs1800790 polymorphism
Description
Identification of 455G-A, rs1800790 polymorphisms in the FGB gene
Time Frame
2 year
Title
SERPINE (PAI) 1 gene 675 5G/4G, rs1799768 polymorphism
Description
Identification of 675 5G/4G, rs1799768 polymorphisms in the SERPINE (PAI) 1 gene
Time Frame
2 year
Title
CRP gene C3872T, rs1205 polymorphism
Description
Identification of C3872T, rs1205 polymorphisms in the CRP gene
Time Frame
2 year
Title
IL17A gene G-197A, rs2275913 polymorphism
Description
Identification of G-197A, rs2275913 polymorphisms in the IL17A gene
Time Frame
2 year
Title
IL2 gene T-330G, rs2069762 polymorphism
Description
Identification of T-330G, rs2069762 polymorphisms in the IL2 gene
Time Frame
2 year
Title
IL10 gene C-592A, rs1800872 polymorphism
Description
Identification of C-592A, rs1800872 polymorphisms in the IL10 gene
Time Frame
2 year
Title
TNF gene G-308A, rs1800629 polymorphism
Description
Identification of G-308A, rs1800629 polymorphisms in the TNF gene
Time Frame
2 year
Title
CRP gene A-717G, rs2794521 polymorphism
Description
Identification of A-717G, rs2794521 polymorphisms in the CRP gene
Time Frame
2 year
Title
IL6 gene C-174G, rs1800795 polymorphism
Description
Identification of C-174G, rs1800795 polymorphisms in the IL6 gene
Time Frame
2 year
Title
TLR2 gene Arg753Gln, rs5743708 polymorphism
Description
Identification of Arg753Gln, rs5743708 polymorphisms in the TLR2 gene
Time Frame
2 year
Title
TLR3 gene Phe412Leu, rs3775291 polymorphism
Description
Identification of Phe412Leu, rs3775291 polymorphisms in the TLR3 gene
Time Frame
2 year
Title
TLR4 gene Asp299Gly, rs4986790 polymorphism
Description
Identification of Asp299Gly, rs4986790 polymorphisms in the TLR4 gene
Time Frame
2 year
Title
TLR6 gene Ser249Pro, rs5743810 polymorphism
Description
Identification of Ser249Pro, rs5743810 polymorphisms in the TLR6 gene
Time Frame
2 year
Title
TLR9 gene T-1237C, rs5743836 polymorphism
Description
Identification of T-1237C, rs5743836 polymorphisms in the TLR9 gene
Time Frame
2 year

10. Eligibility

Sex
Female
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: women under 45 years old presence of premature ovarian insufficiency in the medical history Exclusion Criteria: male gender age over 45 years
Facility Information:
Facility Name
Sergey Vladimirovich Lopukhov
City
Ryazan
State/Province
Ryazan Region
ZIP/Postal Code
390044
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
No

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

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