SNPMiner Trials (Home Page)
Report for Mutation R16G
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 ß2 Adrenergic Receptor Polymorphisms and Vasodilation of Internal Mammary Artery Induced by Isoproterenol
Single nucleotide polymorphisms at codon 46 and 79 of the gene encoding for the ß2 adrenergic receptor (ß2AR) modify its pharmacological properties and may alter the response to ß2AR agonists. The goal of the present study was to evaluate the role played by the Arg16Gly and Gln27Glu polymorphisms on isoproterenol induced relaxation of internal mammary arteries segments ex-vivo. Internal mammary leftover segments were collected from 96 patients undergoing coronary artery bypass graft operation. Four rings that were prepared from each specimen were allowed to reach equilibrium with physiological Krebs solution prior to precontraction with U46619. Using the organ bath technique, cumulative dose response curve of isoproterenol was constructed and mean EC50 calculated for each patient.
NCT00226551 Coronary Disease Drug: Isoproterenol MeSH:Coronary Disease
The goal of the present study was to evaluate the role played by the Arg16Gly and Gln27Glu polymorphisms on isoproterenol induced relaxation of internal mammary arteries segments ex-vivo. --- Arg16Gly ---
Primary Outcomes
Measure: Mean Ec50% in response to rising concentration of isoproterenol2 Efficacy and Safety of Increasing Doses of Inhaled Albuterol Administered by Metered Dose Inhalers in Children With Acute Wheezing Episodes
Metered dose inhalers with spacers are devices capable of providing higher rates of lung deposition of drugs such as beta agonists when compared to conventional nebulizers, but there is no consensus about the optimal dose when this is the device of choice and there is evidence that younger children need proportionally higher doses of albuterol (in μg/kg) when compared to older children. Other factors that may interfere with response to albuterol treatment include the genetics of the beta adrenergic receptor (ADRβ2) and infectious etiology of the wheezing attack. This study will assess the effectiveness of a dose regimen that prioritizes higher doses of albuterol, with doses in μg/kg higher for younger children. Security of this new dosing regimen will be assessed by monitoring clinical side effects and serum levels of albuterol, but the investigators will also examine the presence of 12 different respiratory viruses in these patients and evaluate the influence of ADRβ2 receptor genetics in the response to albuterol. The primary outcome measure will be the need for hospitalization. Secondary outcomes will include a change in clinical score, respiratory rate and forced expiratory volume in the first second, the need for additional treatments and length of stay in the emergency room for those not hospitalized.
NCT01323010 Asthma Children Drug: Albuterol - Experimental Drug: Albuterol - Control MeSH:Respiratory Sounds
HPO:Crackles Rhonchi Stridor Wheezing
Admission rates in patients with and without rhinovirus detected by PCR in nasal lavage samples.. Admission Rates in Patients With the Arg16Gly Polymorphisms. --- Arg16Gly ---
Admission rates in patients with the Arg16Gly polymorphisms of the beta-2 adrenergic receptor (Arg16Gly, Arg16Arg and Gly16Gly genotypes).. Inclusion Criteria: 1. Aged 2 to 18 years; 2. History of two or more previous episodes of wheezing treated with bronchodilators in the last year; 3. Wheezing attacks characterized by coughing, difficulty breathing and auscultation of expiratory wheezing or prolonged expiration; 4. Intensity of wheezing attacks defined by PRAM score as moderate or severe (PRAM ≥ 5). --- Arg16Gly ---
Admission rates in patients with the Arg16Gly polymorphisms of the beta-2 adrenergic receptor (Arg16Gly, Arg16Arg and Gly16Gly genotypes).. Inclusion Criteria: 1. Aged 2 to 18 years; 2. History of two or more previous episodes of wheezing treated with bronchodilators in the last year; 3. Wheezing attacks characterized by coughing, difficulty breathing and auscultation of expiratory wheezing or prolonged expiration; 4. Intensity of wheezing attacks defined by PRAM score as moderate or severe (PRAM ≥ 5). --- Arg16Gly --- --- Arg16Gly ---
To genotype the ADBR2 receptor (blood samples), the gene regions encompassing the Arg16Gly, Gln27Glu, and Arg19Cys Thr164Ile polymorphisms will be amplified via PCR. --- Arg16Gly ---
Primary Outcomes
Description: Hospital admission was defined as the need to stay in the emergency room for more than 4 hours, due to the failure to meet the discharge criteria (PRAM score ≤ 3 and pulse oximetry, ≥ 92%)
Measure: Hospital Admission Time: Starting at 4 hours post-treatmentSecondary Outcomes
Description: Change in FEV1 one hour post-treatment in comparison with baseline. Spirometry was performed only in subjects older than 6 years and who could perform the maneuver properly.
Measure: Forced Expiratory Volume in the First Second Time: One hour post-treatment in comparison with baselineDescription: Change in the Pediatric Respiratory Assessment Measure (PRAM) score one hour post-treatment in comparison with baseline. The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack. We calculated the difference between the PRAM score measured one hour post treatment and the PRAM score at baseline (PRAM score 1 hour - PRAM score baseline). The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2). minimum value of the difference (Albuterol - Higher Dose, experimental group): -8 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0 minimum value of the difference (Albuterol - Lower Dose, control group): -8 maximum value of the difference (Albuterol - Lower Dose, control group): 0
Measure: Change in PRAM Score After One Hour Time: One hour post-treatmentDescription: Albuterol determination in the plasma was carried out at at discharge or hospital admission (up to 4 hours post treatment), dosage was accomplished by High Performance Liquid Chromatography.
Measure: Albuterol Determination in the Plasma Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: Changes in glucose serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Glucose Serum Levels Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Electrocardiogram performed at baseline
Measure: Electrocardiogram at Baseline Time: at baselineDescription: Change in respiratory rate one hour post-treatment in comparison with baseline.
Measure: Changes in Respiratory Rate After One Hour Time: One hour post-treatment in comparison with baselineDescription: The need for additional therapies such as magnesium sulphate or intravenous albuterol were recorded
Measure: Need for Additional Therapies Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: Change in the Pediatric Respiratory Assessment Measure (PRAM) score at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline. The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack. We calculated the difference between the PRAM score measured at discharge or admission and the PRAM score at baseline (PRAM score discharge or admission - PRAM score baseline). The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2). minimum value of the difference (Albuterol - Higher Dose, experimental group): -9 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0 minimum value of the difference (Albuterol - Lower Dose, control group): -9 maximum value of the difference (Albuterol - Lower Dose, control group): 1
Measure: Changes in PRAM Score at Discharge or Hospital Admission Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Changes in potassium serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Potassium Serum Levels Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Changes in bicarbonate serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Bicarbonate Serum Levels Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Changes in respiratory rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Respiratory Rate at at Discharge or Hospital Admission. Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Change in pulse oximetry one hour post-treatment in comparison with baseline
Measure: Change in Pulse Oximetry One Hour Post-treatment Time: One hour post-treatment in comparison with baselineDescription: Changes in pulse oximetry at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Pulse Oximetry at Discharge or Hospital Admission. Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.Description: Change in heart rate one hour post-treatment in comparison with baseline.
Measure: Changes in Heart Rate After One Hour Time: One hour post-treatment in comparison with baselineDescription: Changes in heart rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.
Measure: Changes in Heart Rate at Discharge or Hospital Admission Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: Electrocardiogram one hour post-treatment to identify possible rhythm disturbances.
Measure: Electrocardiogram One Hour Post-treatment. Time: One hour post-treatmentDescription: Electrocardiogram at discharge or hospital admission to identify possible rhythm disturbances.
Measure: Electrocardiogram at Discharge or Hospital Admission Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: lengths of stay in the emergency room for discharged patients
Measure: Lengths of Stay in the Emergency Room Time: one to four hoursDescription: Admission rates in patients with and without any of the following viruses detected by PCR in nasal lavage samples: Adenovirus; Bocavirus; Coronavirus; Enterovirus (Echovirus); Influenza (A H3N2, A H1N1/2009, B and C); Metapneumovirus (subtypes A and B); Parainfluenza 1, 2, 3 and 4 (subtypes A and B); Rhinovirus; Respiratory Syncytial Virus type A and Respiratory Syncytial Virus type B.
Measure: Admission Rates in Patients With and Without Any Virus Detected Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: Admission rates in patients with and without rhinovirus detected by PCR in nasal lavage samples.
Measure: Admission Rates in Patients With and Without Rhinovirus Detect Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)Description: Admission rates in patients with the Arg16Gly polymorphisms of the beta-2 adrenergic receptor (Arg16Gly, Arg16Arg and Gly16Gly genotypes).
Measure: Admission Rates in Patients With the Arg16Gly Polymorphisms Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)3 Pharmacogenetics Use For Further Treatment Improvement in childreN
There is large heterogeneity in treatment response to asthma medication and a one-size fits all approach based on current guidelines might not fit all children with asthma. It is expected that children with one or more variant alleles (Arg16Arg and Arg16Gly) within the beta2 adrenergic receptor (ADRB2) gene coding for the beta2-receptor have a higher risk to poorly respond to long-acting beta2-agonists (LABA) comparing to the Gly16Gly wildtype. Aims To study whether ADRB2 genotype-guided treatment will lead to improvement in asthma control in children with uncontrolled asthma on inhaled corticosteroids compared with usual care. Design A multicentre, double-blind, precision medicine, randomized trial will be carried out within 20 Dutch hospitals. 310 asthmatic children (6-17 years of age) not well controlled on a low dose of inhaled corticosteroids (ICS) will be included and randomized over a genotype-guided and a non-genotype-guided(control) arm. In the genotype-guided arm children with Arg16Arg and Arg16Gly will be treated with double dosages of ICS and with the Gly16Gly wildtype with add on LABA. In the control arm children will be randomized over both treatment options. Lung function measurements, questionnaires focussing on asthma control (ACT/c-ACT) and quality of life, will be obtained in three visits within 6 months. The primary outcome will be improvement in asthma control based on repeated measurement analysis of c-ACT or ACT scores in the first three months of the trial. Additional cost effectiveness studies will be performed. Conclusion Currently, pharmacogenetics is not used in paediatric asthmas. This trial may pave the way to implement promising results for genotype-guided treatment in paediatric asthma in clinical practice.
NCT03654508 Asthma in Children Genetic: ADRB2-genotype guided treatment Other: Randomisation
It is expected that children with one or more variant alleles (Arg16Arg and Arg16Gly) within the beta2 adrenergic receptor (ADRB2) gene coding for the beta2-receptor have a higher risk to poorly respond to long-acting beta2-agonists (LABA) comparing to the Gly16Gly wildtype. --- Arg16Gly ---
In the genotype-guided arm children with Arg16Arg and Arg16Gly will be treated with double dosages of ICS and with the Gly16Gly wildtype with add on LABA. --- Arg16Gly ---
Furthermore, to test the hypothesis it is necessary to include enough children in the control group with Arg16Arg or Arg16Gly to be treated with LABA. --- Arg16Gly ---
This will lead to an estimated number of children with Arg16Arg or Arg16Gly of 51 who will get LABA add on. --- Arg16Gly ---
Primary Outcomes
Description: Patients will fill in the (childhood-)Asthma Control Test at baseline, after 3 months [Range score: 0 - 27, 20 or more means asthma under control]
Measure: Asthma control based on (childhood-)Asthma Control Test scores in the first 3 months of the trial Time: 3 monthsSecondary Outcomes
Description: Patients will fill in the (childhood-)Asthma Control Test at baseline after 6 months [Range score: 0 - 27, 20 or more means asthma under control]
Measure: Change in asthma control at t=6 months (childhood-)Asthma Control Test Time: 6 monthsDescription: Patients will fill in a questionnaire about asthma-related school absences [Minimum score 0 days, maximum score more than 10 days]
Measure: Change in asthma-related school absences Time: 6 monthsDescription: Patients will be questioned what kind of treatment they use at baseline visit, after three months
Measure: Change in therapy in t = 3 months Time: 3 monthsDescription: Patients will fill in the (childhood-)Asthma Control Test at baseline, every month [Range score: 0 - 27, 20 or more means asthma under control]
Measure: Time to reach asthma control (Asthma Control Test score ≥20) Time: 6 monthsDescription: Patients will fill in the Productivity Cost Questionnaire at 0, 3 and 6 months. The IPCQ measures: absenteeism (number of days missed from work in the 4 weeks due to ilness) -- minimum is 0, maximum (in theory) is 28 days Presenteism (productivity lost while at work due to ilness) -- minimum is 0, maximum is 224 hours. In absenteeism, a lower number of days missed from work represent a better outcome; In presenteism, a lower number of hours represent a better outcome For presenteism the number of hours productivity loss is calculated by the following formula using data from the questionnaire. presenteism = number of workingdays affected by illness * (1-efficiencyscore/10)*working hours per working day. This results in a monetary value for productivity loss.
Measure: Cost-effectiveness of ADRB2 genotype guided treatment measured by the Productivity Cost Questionnaire Time: 3 and 6 monthsDescription: Non-response to ICS treatment will be measured by analysing feces samples (microbiome) and nose swabs (epigenome). Nose swabs will be collected after 0, 3 and 6 months and feces after 1 month
Measure: In-depth integrative -omics analysis Time: 0, 3 and 6 monthsDescription: Measured by the Pediatric Asthma-related Quality of Life Questionnaire (PAQLQ). Children are asked to think about how they have been during the previous week and to respond to each of the 32 questions on a 7-point scale (7 = not bothered at all - 1 = extremely bothered). The overall PAQLQ score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains. Subscales are summed.
Measure: Change in quality of life assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) score Time: 0, 3 and 6 monthsDescription: Measured by the PedsQL questionnaire, a 23 item generic score scale consisting of physiological functioning, emotional functioning, social functioning and school functioning questions with multidimensional scales. Subscales are summed. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.
Measure: Change in fatigue scores assessed by the PedsQL questionnaire Time: 0, 3 and 6 monthsDescription: FEV1 will be measured at 0 and 3 months, change in FEV1 will be calculated.
Measure: change in FEV1 at t = 3 months Time: 0 and 3 monthsDescription: FEV1 will be measured at t=0 and 6 months, change in FEV1 will be calculated
Measure: change in FEV1 at t = 6 months Time: 0, 3 and 6 monthsDescription: Exhaled nitric oxide measures will be performed using the Niox Vero at t=0 and 3 months
Measure: change in fraction of exhaled nitric oxide at t=3 months Time: 0 and 3 monthsDescription: Exhaled nitric oxide measures will be performed using the Niox Vero at t=0. 3 and 6 months
Measure: change in fraction of exhaled nitric oxide at t=6 months Time: 0,3 and 6 months