SNPMiner Trials by Shray Alag
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SNPMiner Trials (Home Page)
Report for Mutation A1166C
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 4 clinical trials
Clinical Trials
1 Optimal Dose of Irbesartan for Renoprotection in Type 2 Diabetic Patients With Persistent Microalbuminuria
Aim: To evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultra high doses of irbesartan in Type 2 diabetic patients with microalbuminuria Design: A double-masked randomized cross-over trial including 60 hypertensive Type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication. At inclusion, previous antihypertensive treatment will be discontinued and replaced with bendroflumethiazide 5 mg o.d. for the entire study. Following two months wash-out (baseline), patients will be treated randomly with irbesartan 300, 600 and 900 mg o.d., each dose for two months. End-points evaluated at the end of each study period include urinary albumin excretion rate (UAE, mean of three 24-hrs collections), 24-hrs blood pressure (ABP); and GFR (51Cr-EDTA).
NCT00320879 Conditions
- Type 2 Diabetes
- Microalbuminuria
Interventions
- Drug: irbesartan
MeSH:Albuminuria
HPO:Albuminuria
Initially we will evaluate the influence of the ACE/ID- , Angiotensin II type I receptor (A1166C) - and the angiotensinogen (M235T) polymorphisms. --- A1166C ---
Primary Outcomes
Measure: urinary albumin excretion rateSecondary Outcomes
Measure: ambulatory blood pressureMeasure: glomerular filtration rate
Measure: serum potassium
Measure: serum creatinine
Measure: lipids
Measure: renin
Measure: aldosterone
Measure: NT-proBNP
Measure: markers of endothelial function
Measure: markers of inflammation
Measure: genotypes with possible implications for the risk of cardiovascular disease
2 A Randomized, Open Label, Cross-over Comparative Study of Irbesartan/Hydrochlorothiazide and Irbesartan in the Treatment of Mild to Moderate Hypertension
Primary: 1. To compare the change in forearm vascular resistance following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To assess changes of serum proinflammatory cytokine, markers of cardiovascular risks, oxidative stress and circulating adhesion molecule including thiobarbiturate acid reactive substances (TBARS), C-reactive protein (CRP), interleukin 6 (IL-6), and vascular cell adhesion molecule 1 (VCAM-1). Secondary: 1. To compare the reduction in office blood pressure following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To compare the response rate (defined as office Systolic blood pressure(SBP)/diastolic blood pressure (DBP) reduce more than 10mmHg from baseline), and BP controlled rate (defined as SBP<140 mmHg and /or DBP<90 mmHg) 3. To ascertain the safety and tolerability of irbesartan / hydrochlorothiazide versus irbesartan when administered once daily 4. To determine whether angiotensin II type 1 (AT-1) receptor gene polymorphisms (including A1166C gene with about 4% of the minor allele frequency in Chinese population and other single nucleotide polymorphisms with a higher frequency of about 10% of minor allele) is related to reduction of BP
NCT00443612 Conditions
- Hypertension
Interventions
- Drug: Irbesartan/Hydrochlorothiazide
- Drug: Irbesartan
MeSH:Hypertension
HPO:Hypertension
To compare the reduction in office blood pressure following a 12-week regimen of irbesartan/hydrochlorothiazide versus irbesartan 2. To compare the response rate (defined as office Systolic blood pressure(SBP)/diastolic blood pressure (DBP) reduce more than 10mmHg from baseline), and BP controlled rate (defined as SBP<140 mmHg and /or DBP<90 mmHg) 3. To ascertain the safety and tolerability of irbesartan / hydrochlorothiazide versus irbesartan when administered once daily 4. To determine whether angiotensin II type 1 (AT-1) receptor gene polymorphisms (including A1166C gene with about 4% of the minor allele frequency in Chinese population and other single nucleotide polymorphisms with a higher frequency of about 10% of minor allele) is related to reduction of BP Forearm vascular resistance. --- A1166C ---
Primary Outcomes
Measure: Forearm vascular resistance Time: At baseline and end of studyMeasure: Changes of serum TBARS, CRP, IL-6, and VCAM-1 Time: Throughout the study period
Measure: Office BP measurement of seated SBP and DBP Time: At baseline and after 12-week treatment
Measure: Adverse events Time: Throughout the study period
Secondary Outcomes
Measure: Office BP measurement of seated SBP and DBP Time: At baseline and after 12-week treatment3 Observational Study of the Polymorphisms of the Renin-angiotensin-aldosterone System and Their Relation to Resistant Systemic Arterial Hypertension and Adverse Cardiovascular Events
Renin-angiotensin-aldosterone system (RAAS) polymorphisms influence 24h arterial pressure fluctuation. Resistant systemic arterial hypertension (RSAH) has an increased risk of end organ damage and unfavourable prognosis, whereas pseudo-RSAH usually respond favourably to drug therapy. To prospectively investigate, in subjects with RSAH in a tropical South American city: 1) Adverse cardiovascular events defined as fatal and non-fatal stroke or acute myocardial infarction (AMI); and 2) the association of RAAS polymorphisms and adverse cardiovascular events in this population. Study population: 212 hypertensives recruited from primary care assistance (time since first diagnosis of hypertension: 16.5±8.1 years) and without appropriate pressure control, between 2001 and 2006, corresponding to 0.48% of all hypertensives under care (18 new cases/year), 57±10 years old, 66% females. Under drug treatment schedule: three or more drugs including a diuretic. Ninety two randomly selected hypertensives basis had renin-angiotensin-aldosterone system genetic profile determined. Genetic assessment was carried out using a polymerase chain reaction assay amplification technique. The following single nucleotide polymorphisms were analyzed: renin (G1051A), angiotensinogen (M235T), angiotensin converting enzyme-ACE (I/D), angiotensin II type 1 receptor (A1166C), aldosterone synthase (C344T) and mineralocorticoid receptor (G3514C).
NCT01173029 Conditions
- Systemic Arterial Hypertension
- Hypertension Resistant to Conventional Therapy
- Myocardial Infarction
- Stroke
Interventions
- Drug: Anti-hypertensive drug treatment
MeSH:Hypertension Myocardial Infarction Coronary Vasospasm Infarction
HPO:Hypertension Myocardial infarction
The following single nucleotide polymorphisms were analyzed: renin (G1051A), angiotensinogen (M235T), angiotensin converting enzyme-ACE (I/D), angiotensin II type 1 receptor (A1166C), aldosterone synthase (C344T) and mineralocorticoid receptor (G3514C). --- G1051A --- --- M235T --- --- A1166C ---
Primary Outcomes
Description: Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography. Death was considered to be related to the event if occurring up to 30 days after the acute event. Assessment twice an year by active and direct contact to patients or relatives and review of medical records.
Measure: Strokes, Either Fatal or Nonfatal Time: up to 10 yearsSecondary Outcomes
Description: Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography. Evidence of clinically definite acute myocardial infarction (prolonged > 20min chest pain, not relieved by sublingual nitrate, ST-T segment deviation on 12-lead surface ECG, elevation of plasma troponin >0.2 ng/dL 6h following chest pain episode). Death was considered to be related to the event if occurring up to 30 days after the acute event. Assessment twice an year by active and direct contact to patients or relatives and review of medical records.
Measure: Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal Time: up to 10 years4 Investigating the Involvement of ACE and Angiotensinogen Genes' Polymorphism Along With Other Thrombophilic Genotypes in Severe Forms of COVID-19 With/Without Thrombotic Events
An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. A major public health question remains to be investigated: why COVID-19 is mild for some, critically severe for others and why only a percentage of COVID-19 patients develop thrombosis, despite the disease's proven hypercoagulable state? Patients' intrinsic characteristics might be responsible for the deep variety of disease forms. Our study aims to assess the validity of the hypothesis according to which underlining genetic variations might be responsible for different degrees of severity and thrombotic events risks in the novel coronavirus disease. Moreover, we suspect that prothrombotic genotypes occuring in the genes that encode angiotensin-converting enzyme (ACE-DEL/INS) and angiotensinogen (AGT M235T) are involved in the unpredictable evolution of COVID-19, both in terms of severity and thrombotic events, due to the strong interactions of SARS-CoV-2 with the renin-angiotensin-aldosterone system (RAAS). Therefore, we also aim to assess the validity of the theory according to which there is a pre-existing atypical modulation of RAAS in COVID-19 patients that develop severe forms and/or thrombosis. Our hypothesis is based on various observations. Firstly, there is a substantial similarity with a reasonably related condition such as sepsis, for which there is a validated theory stating that thrombophilic mutations affect patients' clinical response. Secondly, racial and ethnic genetic differences are responsible for significant dissimilar thrombotic risks among various nations. Thirdly, an increase in stroke incidence has been reported in young patients with COVID-19, without essential thrombosis risk factors, favoring the idea that a genetic predisposition could contribute to increase the thrombotic and thromboembolic risk. Fourthly, the plasminogen activator inhibitor (PAI)-1 4G/5G inherited mutation was found to be responsible for a thrombotic state causing post-SARS osteonecrosis.
NCT04519398 Conditions
- Covid19
- Corona Virus Infection
- Thrombosis
- ARDS
- Thrombophilia
- Thromboses, Intracranial
- Thromboses, Deep Vein
- RAAS
Interventions
- Genetic: Complete thrombophilic profile testing by multiplex PCR
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Intracranial Thrombosis Thrombosis Venous Thrombosis Thrombophilia
HPO:Deep venous thrombosis Hypercoagulability Venous thrombosis
Inclusion Criteria: - All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test Exclusion Criteria: - Patient refusal - Uncertain tests results - Children Inclusion Criteria: - All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test Exclusion Criteria: - Patient refusal - Uncertain tests results - Children Covid19 Corona Virus Infection Thrombosis ARDS Thrombophilia Thromboses, Intracranial Thromboses, Deep Vein RAAS Coronavirus Infections Severe Acute Respiratory Syndrome Intracranial Thrombosis Thrombosis Venous Thrombosis Thrombophilia The study's protocol will cover the following steps: • Collected data from COVID-19 patients at admission will include: - Descriptive general demographic data - Previous pathologies and thrombosis risk factors - Routine biological data (the blood routinely collected will also be used for SARS-Cov-2 specific RT-PCR exam) Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes: - Factor V Leiden - Factor V 4070 A G (Hr2) - Factor II G20210A - Methylenetetrahydrofolate reductase (MTHFR) C677T - MTHFR A1298C - Cystathionine β-synthase (CBS) 844ins68 - PAI-1 4G/5G - Glycoprotein IIIa T1565C (HPA-1a/b) - ACE-DEL/INS - Apolipoprotein E (ApoE) - AGT M235T - Angiotensin II type 1 receptor (ATR-1) A1166C - Fibrinogen - 455 G A - Factor XIII Val34Leu SpO2, respiratory rate, PaO2/FiO2 RAAS components - Imagistic procedures (chest X-ray or CT) - All patients with a positive SARS-CoV-2 PCR test will be included - Patients will be divided into three groups depending on disease severity and the presence of thrombotic state: - 1st group includes COVID-19 patients with proved - venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms) - or arterial thrombosis (heart attacks, strokes) - 2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 ≥ 94% - 3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50% - Statistical methods will be employed to check for significant differences between prothrombotic mutations frequency and RAAS components levels for the three groups --- G20210A --- --- C677T --- --- A1298C --- --- T1565C --- --- M235T --- --- A1166C ---
Primary Outcomes
Description: The difference of prothrombotic genotypes frequency between the three groups
Measure: Number of patients with thrombophilic profile alterations Time: One yearSecondary Outcomes
Description: The differences of RAAS components levels between the three groups
Measure: Number of patients with RAAS components alterations Time: One year