Clinical trial NCT04943354: 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
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: Ryazan State Medical University
Sponsor class: OTHER
First posted: 2021-06-29
Enrollment: 238
Sex: FEMALE
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Age (years)
timeFrame: 2 year
Secondary outcomes:
measure: Menarche (years)
timeFrame: 2 year
Other outcomes:
measure: Pregnancy (number)
timeFrame: 2 year
measure: Childbirth (number)
timeFrame: 2 year
measure: Menopause (yes/no)
timeFrame: 2 year
measure: Surgical removal of both ovaries (yes/no)
timeFrame: 2 year
measure: Presence of amenorrhoea (at least 4 months) (yes/no)
timeFrame: 2 year
measure: Follicle stimulating hormone (FSH) level (mMed/ml)
timeFrame: 2 year
measure: Age at menopause (years)
timeFrame: 2 year
measure: Length of post-menopause (years)
timeFrame: 2 year
measure: Taking oral contraceptives (yes/no)
timeFrame: 2 year
measure: Taking hormone replacement therapy (HRT) (yes/no)
timeFrame: 2 year
measure: Length of time on hormone replacement therapy (years)
timeFrame: 2 year
measure: Smoking status (yes/no)
timeFrame: 2 year
measure: Number of cigarettes smoked per day (number)
timeFrame: 2 year
measure: Smoking experience (years)
timeFrame: 2 year
measure: Smoking index (points)
timeFrame: 2 year
measure: Height (cm)
timeFrame: 2 year
measure: Weight (kg)
timeFrame: 2 year
measure: BMI (kg/m2)
timeFrame: 2 year
measure: Waist circumference (cm)
timeFrame: 2 year
measure: Hip circumference (cm)
timeFrame: 2 year
measure: Waist circumference to hip circumference ratio (WHR) (number)
timeFrame: 2 year
measure: Secondary education (yes/no)
timeFrame: 2 year
measure: Secondary vocational education (yes/no)
timeFrame: 2 year
measure: Higher education (yes/no)
timeFrame: 2 year
measure: Systolic blood pressure (mmHg)
timeFrame: 2 year
measure: Diastolic blood pressure (mmHg)
timeFrame: 2 year
measure: Heart rate (number)
timeFrame: 2 year
measure: Radial artery pulse (beats per minute).
timeFrame: 2 year
measure: Arterial hypertension (yes/no)
timeFrame: 2 year
measure: Ultrasound examination of the heart
timeFrame: 2 year
measure: Total cholesterol (mmol/l)
timeFrame: 2 year
measure: High-density lipoproteins (HDL) (mmol/l)
timeFrame: 2 year
measure: Low density lipoproteins LDL (mmol/l)
timeFrame: 2 year
measure: Triglycerides (mmol/l)
timeFrame: 2 year
measure: Cholesterol/HDL ratio (number)
timeFrame: 2 year
measure: Blood glucose level (mmol/l)
timeFrame: 2 year
measure: Glycated haemoglobin (HbA1c), (percent %)
timeFrame: 2 year
measure: Diabetes mellitus (yes/no)
timeFrame: 2 year
measure: Taking antihypertensive medication (yes/no)
timeFrame: 2 year
measure: Taking hypolipidemic medicines (yes/no)
timeFrame: 2 year
measure: Metabolic syndrome (yes/no)
timeFrame: 2 year
measure: Presence of post-menopausal diagnosis: arrhythmia or other rhythm disturbances (yes/no)
timeFrame: 2 year
measure: Presence of a post-menopausal diagnosis of coronary heart disease (yes/no)
timeFrame: 2 year
measure: Presence of a post-menopausal diagnosis of myocardial infarction (yes/no)
timeFrame: 2 year
measure: Presence of post-menopausal diagnosis: thromboembolism (yes/no)
timeFrame: 2 year
measure: Post-menopausal diagnosis of varicose veins in the lower limbs (yes/no)
timeFrame: 2 year
measure: Presence of a post-menopausal diagnosis: Acute cerebral haemorrhage (yes/no)
timeFrame: 2 year
measure: Deaths from cardiovascular disease in the post-menopausal period (yes/no)
timeFrame: 2 year
measure: A history of cancer (yes/no)
timeFrame: 2 year
measure: AGT gene Met235Thr, rs699 polymorphism
timeFrame: 2 year
measure: ACE gene Alu Ins/Del I>D, rs4646994 polymorphism
timeFrame: 2 year
measure: NOS3 gene C786T, rs2070744 polymorphism
timeFrame: 2 year
measure: EDN1 gene Lys198Asn, rs5370 polymorphism
timeFrame: 2 year
measure: ITGB3 gene Leu33Pro, rs5918 polymorphism
timeFrame: 2 year
measure: ITGA2 gene C807T, rs1126643 polymorphism
timeFrame: 2 year
measure: FGB gene 455G-A, rs1800790 polymorphism
timeFrame: 2 year
measure: SERPINE (PAI) 1 gene 675 5G/4G, rs1799768 polymorphism
timeFrame: 2 year
measure: CRP gene C3872T, rs1205 polymorphism
timeFrame: 2 year
measure: IL17A gene G-197A, rs2275913 polymorphism
timeFrame: 2 year
measure: IL2 gene T-330G, rs2069762 polymorphism
timeFrame: 2 year
measure: IL10 gene C-592A, rs1800872 polymorphism
timeFrame: 2 year
measure: TNF gene G-308A, rs1800629 polymorphism
timeFrame: 2 year
measure: CRP gene A-717G, rs2794521 polymorphism
timeFrame: 2 year
measure: IL6 gene C-174G, rs1800795 polymorphism
timeFrame: 2 year
measure: TLR2 gene Arg753Gln, rs5743708 polymorphism
timeFrame: 2 year
measure: TLR3 gene Phe412Leu, rs3775291 polymorphism
timeFrame: 2 year
measure: TLR4 gene Asp299Gly, rs4986790 polymorphism
timeFrame: 2 year
measure: TLR6 gene Ser249Pro, rs5743810 polymorphism
timeFrame: 2 year
measure: TLR9 gene T-1237C, rs5743836 polymorphism
timeFrame: 2 year
Locations:
city: Ryazan
country: Russian Federation
facility: Sergey Vladimirovich Lopukhov
state: Ryazan Region
Study officials:
References: