araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Genetic Determinants of Sudden Cardiac Death

Summary: To evaluate whether genetic variation in selected candidate genes is associated with risk of sudden cardiac death in the general population.

Detailed description: BACKGROUND Sudden cardiac death (SCD) affects 400,000 individuals each year in the U.S. alone. Over half have no evidence of heart disease prior to death, and our ability to identify those at risk and, therefore prevent SCD, is poor. Mutations in cardiac ion channel genes including SCN5A, KCNQ1, KCNH2, KCNE1, KCNE2 and RyR2 have been implicated in monogenic traits with high risk of SCD, such as the long-QT, Brugada, sudden infant death syndrome (SIDS), and catecholaminergic polymorphic ventricular tachycardia. Alterations in ion channel function can result in life-threatening ventricular arrhythmias in diverse disease states. Therefore, sequence variants in these genes that alter function or transcription of these ion channels may confer a predisposition to ventricular arrhythmia and SCD in broader populations.
  DESIGN NARRATIVE This research program proposes to determine if sequence variants in the above and other candidate genes are associated with an increased risk of SCD in apparently-healthy populations. Cases of SCD will be assembled from 5 NIH-funded prospective cohorts with a total of 106,314 individuals with existent blood samples. All cohorts are exceptionally well-characterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints. We will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts for the 6 genes. We will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes (haplotype tag SNPs) in both coding and non-coding regions of candidate genes and SCD risk. We will also test directly for associations between single loci that may have functional significance and SCD risk. An estimated 600 cases of well-documented SCD will be confirmed over the first 3 years of the grant period, and these cases will be matched on age, sex, ethnicity, and geographic location to two control subjects from the same cohort. In addition, based upon known sex difference in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, we will specifically examine sex difference in the risk of SCD associated with sequence variation in these genes. The findings generated will have substantial implications for our understanding of the SCD syndrome and risk stratification in the general population.

Eligibility: No eligibility criteria.

Relevance to patient case: possibly relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Trial to Investigate the Efficacy of Olmesartan in Paroxysmal Atrial Fibrillation

Summary: Hypothesis:
  Blocking the angiotensin (AT) II type 1 receptor (Olmesartan) reduces the incidence of episodes of atrial fibrillation in patients with paroxysmal atrial fibrillation during 12 months by more than 25% compared to standard medication without angiotensin II type 1 receptor.
  A total of 422 subjects will be included in the two study groups. The treatment arm will receive 40mg Olmesartan per day, the remaining patients will receive placebo. Follow-up is 12 months. Daily Tele-ECG recordings will determine the cardiac rhythm and asymptomatic episodes of atrial fibrillation (AF) every day. Concomitant therapy with AV-nodal blocking drugs are allowed during the study. In case of severe AF-induced symptoms, an antiarrhythmic "recovery medication" (amiodarone) is allowed during follow-up.

Detailed description: Double-blind, central randomization, two treatment groups, stratified by beta-blocker use. 211 patients in each treatment arm.

Eligibility: Inclusion Criteria:
  -  Documented paroxysmal atrial fibrillation: ECG documentation of atrial fibrillation at least in one ECG recorded during the last 2 months prior to randomization plus additional ECG recording of sinus rhythm at least 12 hours after the above mentioned ECG documentation.
  -  Age ≥ 18
  -  Patient informed orally and in writing
  -  Written informed consent of the patient
  Exclusion Criteria:
  -  Strong clinical evidence for therapy with AT II/ACE inhibitors
  -  AT II/ACE inhibitor therapy within the last month
  -  Therapy with antiarrhythmic agents of class I or class III within the last month, therapy with amiodarone within the last 3 months
  -  Direct current (DC) cardioversion within the last 3 months
  -  Symptomatic bradycardia
  -  Implanted pacemaker or implanted cardioverter/defibrillator with any antitachycardiac algorithm in use
  -  Cardiac surgery or cardiac catheter ablation within the last 3 months
  -  Typical angina pectoris symptoms at rest or during exercise
  -  Known coronary artery disease with indication for intervention
  -  Valvular disease > II degree
  -  Left ventricular ejection fraction < 40%
  -  Diastolic blood pressure > 110mm Hg at rest
  -  Symptomatic arterial hypotension
  -  Known renal artery stenosis
  -  Serum creatinine > 1.8 mval/l
  -  Relevant hepatic or pulmonary disorders
  -  Hyperthyroidism manifested clinically and in laboratory
  -  Known drug intolerance for AT II inhibitors
  -  Females who are pregnant or breast feeding
  -  Females of childbearing potential who are not using a scientifically accepted method of contraception
  -  Participation in a clinical trial within the last 30 days
  -  Drug addiction or chronic alcohol abuse
  -  Legal incapacity, or other circumstances which would prevent the patient from understanding the aim, nature or extent of the clinical study
  -  Evidence of an uncooperative attitude

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Menevit Study: Menevit Anti-Oxidant Therapy for the Treatment of Male Infertility

Summary: Oxidative stress related damage to sperm is believed to be a major cause of male infertility. The object of the Menevit study is to investigate the role of a novel anti-oxidant preparation (Menevit) on sperm function, embryo quality and pregnancy rates in an in vitro fertilization (IVF) setting.

Detailed description: Men will be screened for oxidative stress (free radical) related damage to their sperm. This will include screening for lipid peroxidation of sperm using the LPO-586 assay, HOST test and for sperm DNA fragmentation using the Tunel technique. Those men found to have free radical related damage will be enrolled in a randomized control trial in which they will receive either the Menevit anti-oxidant or placebo (in a 2:1 randomization ratio respectively). The Menevit anti-oxidant is a capsule containing several different anti-oxidants, taken orally once per day. The placebo is identical in appearance and taste. After 3 months of Menevit/placebo the female partners of these men will undergo an IVF oocyte retrieval operation and embryo transfer. Pregnancy rates and embryo quality will be compared between groups. Changes in semen characteristics (count, motility, morphology, membrane integrity) and lipid peroxidation (LPO-586) plus sperm DNA fragmentation (Tunel assay) will be assessed at trial entry, 6 weeks and 3 months. Comparisons between the patients embryo quality in the IVF cycle immediately before and during the Menevit trial will also be compared when possible

Eligibility: Inclusion Criteria:
  -  Evidence of oxidative stress to sperm on LPO-586 assay or poor HOST result or clinical evidence for oxidative stress (heavy smoker, varicocele, poor motility in the abscence of anti-sperm antibodies etc)
  -  Evidence of significant sperm DNA damage (25% or more DNA fragmentation as assessed by Tunel assay).
  -  Female partner willing to undergo IVF treatment within 3 months of starting Menevit trial
  Exclusion Criteria:
  -  Female partner 40 years of age or older at trial entry.
  -  Significantly reduced ovarian reserve in female partner (day 3-5 FSH > 10 iu/L if no prior IVF cycle or less than 5 oocytes on a prior IVF cycle.
  -  Sperm count below 0.5 million per ml (impossible to conduct all sperm function assays

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Cohorts and Collections: Clinical and Genetic Study of Parkinson's Disease and Epilepsies

Summary: The DNA and Cell Bank of Instituts Federatifs de Recherche (IFR) of Neurosciences has been running for the last 15 years at the Institut National de la Santé Et de la Recherche Médicale (INSERM) Unit 679 (former unit 289). Since its creation, this structure has been the support of research projects in genetics for neurological and psychiatric disorders. The cohorts established have led to discoveries in monogenic disorders, such as cerebellar ataxias, spastic paraplegias, frontotemporal dementias, epilepsies, Parkinson’s and Alzheimer’s disease, Charcot-Marie-Tooth disease and related entities. The research projects based on the study of the genetic bases in Parkinson’s disease and epilepsies are especially developed for this grant.
  Concerning Parkinson’s disease, the project is based on the extension of the existing cohort throughout the French Parkinson’s Disease Study Group network. Concerning epilepsies, this project is the occasion to build this network with the constitution of a new cohort.
  The specific aims of the scientific projects are the following for Parkinson’s disease:
  -  to evaluate the frequency, the nature and the phenotype associated with parkin mutations in familial or sporadic forms of the disease, according to the age at onset, and
  -  to identify the genetic susceptibility factors in Parkinson’s disease with the study of affected sibpairs and with case/controls association studies.
  For epilepsies, the aims are:
  -  to evaluate the frequency, the nature and the phenotype associated with SCN1A, SCNab and GABR2 gene mutations in familial or sporadic forms of the affection associated with febrile seizures, and
  -  to search for an intervention SCN1A, SCN1B and GABRG2 as susceptible genes in these forms of epilepsies.


Eligibility: Inclusion Criteria:
  -  Patients presenting with Parkinson's disease, with a family history or not,
  -  Minors presenting clinical signs of the disease,
  -  Controls (without signs of the disease), matched by sex and age with the patients,
  -  Relatives for the familial cases,
  -  Patients presenting with an epilepsy episode (myoclonic epilepsy of the newborn, with febrile seizures, of the frontal lobe)
  Exclusion Criteria:
  -  Lack of signed informed consent

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: RIGHT: Rhythm ID Going Head-to-Head Trial

Summary: RIGHT is a randomized, prospective, two-arm study that will assess the differential efficacy of VITALITY 2 implantable cardioverter defibrillators (ICDs) using Rhythm ID™ versus selected Medtronic ICDs.

Detailed description: RIGHT will compare the incidence of Ventricular Tachycardia/Fibrillation (VT/VF) therapies delivered for Supraventricular Tachycardia (SVT) episodes using VITALITY 2 devices with Rhythm ID™ to that of ICDs employing other rhythm discrimination algorithms. Appropriateness of therapies will be assessed after independent adjudication of all VT/VF events leading to therapy. Comparisons will be made between device manufacturers across patient populations receiving either a dual- or single-chamber device.

Eligibility: Inclusion Criteria:
  -  Patients who meet current indications for an ICD
  -  Patients who sign and date a Patient Informed Consent form prior to the implant visit
  -  Patients who remain in the clinical care of the enrolling physician in approved centers
  -  Patients who are able to tolerate ICD programming as specifically prescribed in the study protocol
  Exclusion Criteria:
  -  Patients who are in third degree heart block
  -  Patients whose life expectancy is less than 12 months
  -  Patients who have other cardiac surgeries or procedures planned but not yet performed during the duration of the study
  -  Patients who are currently enrolled in another investigational study or registry that would directly impact the treatment or outcome of the current study
  -  Patients who are younger than 18 years of age
  -  Patients who are mentally incompetent and cannot sign a Patient Informed Consent form or comply with the study
  -  Patients who are pregnant or plan to become pregnant during the study

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Adoptive Immunotherapy for CMV Disease

Summary: Treatment strategy of patients:
  Stem cell engraftment (myeloablative or NST) for induction of host vs graft myeloablative transplantation tolerance.
  Whenever indicated, additional post NST DLI given in graded increment, to optimize control of GVHD.
  Preparation of immune donor lymphocytes, either by donor immunization in-vitro with a CMV-specific peptide followed by administration of immunized donor lymphocytes, or by injection of donor lymphocytes and in-vivo sensitization of donor lymphocytes in the patient following DLI.
  Pre-emptive treatment of seronegative patients at risk or patients with documented viremia or CMV disease with CMV-specific donor lymphocytes generated in-vivo in the donor or in the host by peptide immunization.
  Consenting donors will be immunized with CMV-specific peptides, for induction of CTLs in-vivo following subcutaneous inoculation of peptides with adjuvant or donor APC pulsed with relevant peptides.


Eligibility: Inclusion Criteria:
  -  For Patient:
  -  Consenting patients with indication for myeloablative BMT or NST with an HLA matching sibling available, for transplant.
  -  Patients at risk of CMV disease including seronegative patients; patients with seronegative donors, and seronegative donor for sero positive patients.
  -  Patients with resistant CMV viremia or CMV disease not responding to conventional treatment with ganciclovir, or Foscarnet.
  -  Patients with HLA phenotype for which a relevant peptide for CMV exists.
  -  For Donor:
  -  Consenting sibling >18 years old.
  -  HLA phenotype for which a relevant peptide for CMV exists.
  Exclusion Criteria:
  -  For Patient:
  -  Patients with severe resistant GVHD where there may be a risk to administer DLI or immunized donor lymphocytes.
  -  For Donor:
  -  Consenting sibling >18 years old.
  -  HLA phenotype for which a relevant peptide for CMV exists.
  -  Donor with an infectious disease (e.g. HIV-1; HBV, etc.)

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: A Study to Determine the Safety and Efficacy of Imatinib Mesylate in Patients With Idiopathic Hypereosinophilic Syndrome

Summary: The objectives of the study are:
  1. Evaluation of the safety profile of imatinib mesylate in patients with idiopathic hypereosinophilic syndrome resistant or refractory to, or intolerant of, prednisone, hydroxyurea or interferon-alpha, or untreated patients carrying the Fip1L1-PDGFRA fusion protein.
  2. Evaluation of the efficacy of imatinib mesylate in patients with idiopathic hypereosinophilic syndrome
  3. Analysis of patient's blood samples for the detection of activated kinases.


Eligibility: Inclusion Criteria:
  Idiopathic hypereosinophilic syndromes are included provided they belong to one of the following categories:
  1. previously treated and showing documented resistance or refractoriness to, or intolerance of, prednisone, hydroxyurea or interferon-alpha.
  2. not previously treated but with documented Fip1L1-PDGFRA fusion protein
  Exclusion Criteria:
  -  Other diseases associated with hypereosinophilia
  -  Serum creatinine, serum bilirubin, AST, ALT more than twice the upper normal limit.
  -  ECOG performance status >3
  Other protocol-defined exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Investigation of Cognitive Function Before and After Induced Ventricular Fibrillation in Electrophysiological (EP) Study

Summary: In this study, changes in electroencephalogram (EEG) and the hemodynamic state during ventricular fibrillation or induced ventricular tachycardia are investigated.

Detailed description: Patients with a high risk of malignant tachyarrhythmia are routinely investigated by programmed electrophysiological study (EPS). To investigate the hemodynamic effects of ventricular arrhythmia to cerebral circulation an EEG and transcranial ultrasound are conducted simultaneously during the EPS. Before and after the EPS a neuropsychological test and an investigation of a specific blood sample (Neuron Specific Enolase, NSE) is done.

Eligibility: Inclusion Criteria:
  -  Age > 18 years
  -  Positive agreement
  -  EPS for primary and secondary prophylaxis of a malignant ventricular tachyarrhythmia:
  -  primary prophylaxis: Brugada syndrome, long QT syndrome, cardiomyopathy, short QT syndrome
  -  secondary prophylaxis: Multicenter Automatic Defibrillator Implantation Trial (MADIT) criteria, syncope, documented ventricular tachycardia
  Exclusion Criteria:
  -  Severe neurological deficit
  -  Cardiopulmonary resuscitation

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases

Summary: The aim of this study is the identification of familial congenital arrhythmogenic disorders and their clinical follow-up.

Detailed description: Molecular genetic screening in patients with:
  -  supraventricular
  -  ventricular arrhythmia
  -  syncopes of unknown origin and/or suspicion of an arrhythmogenic origin
  -  family members of patients with sudden cardiac death and aborted sudden cardiac death
  Examination of patients includes routine testing like electrocardiogram (ECG), sequential ECGs, exercise testing, invasive electrophysiological stimulation, cardiac magnetic resonance imaging, intravenous drug challenge for identification/exclusion of eg Brugada syndrome. Examples are patients with Long QT Syndrome, Short QT Syndrome, Brugada Syndrome, familial atrial fibrillation, WPW-syndrome, arrhythmias due to familial hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia. Blood samples are taken for further molecular genetic screening.

Eligibility: Inclusion Criteria:
  -  Patients with a history of syncope, abnormal ECG and suspicion of an arrhythmogenic disease
  -  Patients with long QT syndrome
  -  Patients with short QT syndrome, shortened QT intervals, borderline shortened QT intervals
  -  Patients with Brugada syndrome
  -  Patients with hypertrophic cardiomyopathy
  -  Patients with arrhythmogenic right ventricular dysplasia
  Exclusion Criteria:
  -  Inability to understand study protocol

Relevance to patient case: not relevant
Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Safety and Efficacy of SR121463B in Patients With Syndrome of Inappropriate Antidiuretic Hormone Secretion

Summary: To determine the long-term safety and tolerability of SR121463B in patients with syndrome of inappropriate antidiuretic secretion (SIADH). To assess the long-term efficacy of SR121463B in maintaining normal levels of serum sodium in patients with SIADH.
  Long term safety is evaluated further in an open label extension study with flexible doses of satavaptan.


Eligibility: Inclusion Criteria:
  -  Male or female patients aged 18 years and higher.
  -  SIADH (the diagnosis of SIADH is based on several criteria including true serum hypoosmolality, inappropriate urinary osmolality, clinical euvolemia, elevated urinary sodium excretion while on normal salt and water intake, and normal renal, adrenal, and thyroid functions: drug induced SIADH will be limited to carbamazepine or derivatives and antidepressants in patients in whom these drugs cannot be discontinued or easily replaced by other drugs)
  -  Serum sodium between 115 and 132 mmol/L (at least two consecutive serum sodium levels of at least 24 hours apart, from Day -6 to Day -1); for sodium levels between 125 and 132 mmol/L, the spontaneous serum sodium increase between the two assessments on Day -1 should be < 4 mmol/L
  -  Urinary osmolality >200mOsm/kg H2O
  -  Urinary sodium > 30 mmol/L
  Exclusion Criteria:
  -  Patients with acute postoperative SIADH
  -  Presence of dilutional hyponatremia in hypervolemic states such as congestive heart failure and liver disease with ascites
  -  Presence of signs of hypovolemia (e.g., orthostatic hypotension, increased serum urea nitrogen, increased serum albumin, increased hematocrit, …)
  -  Administration of other V2 receptor antagonists or demeclocycline or lithium within one month, thiazides diuretics or spironolactone within 15 days, and urea or loop diuretics within two days prior to study drug administration
  -  Patients with known treated or untreated adrenal deficiency
  -  Presence of untreated hypothyroidism
  -  Presence of uncontrolled diabetes with fasting glycemia > 200 mg/dL (> 11.09 mmol/L)
  -  Presence of clinical and/or electrocardiographical signs of acute myocardial infarction or acute ischemia, or any other clinically significant abnormality according to the Investigator on a 12 lead ECG recording
  -  Administration of inducers of CYP3A4 (phenytoin, rifampin, Saint John's Wort) or potent and moderate inhibitor so CYP3A4within two weeks prior to study drug administration
  -  Inadequate hematological, renal and hepatic functions; hemoglobin (Hb) < 9 g/dL, neutrophils < 1,500/mm3, platelets <100,00/mm3, serum creatine >175 µmol/L (or clearance of creatine <30mL/min for where Ethics Committees require this parameter), ALT and /or AST >2x upper limit of normal
  -  QTcB > 500 ms
  -  Serum potassium > 5 mmol/L

Relevance to patient case: not relevant