araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome

Summary: The purpose of the study is to provide comprehensive follow-up in patients with Long QT Syndrome (LQTS) and gain additional information regarding genotype-phenotype correlation and effective management and treatment options.


Eligibility: Inclusion Criteria:
  -  Children and/or young adults diagnosed with heterogeneous repolarization disorder who have genotype positive Long QT, or
  -  Newly diagnosed mutation positive patients with a confirmed test
  Exclusion Criteria:
  -  Children who are phenotypically positive with no molecular testing
  -  Children that are phenotypically positive but genotype negative

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Nebulized Bronchodilators and Cardiac Repolarization

Summary: Patients of the ICU's often require bronchodilatory treatment due to bronchospasm caused by conditions like : acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) or asthma. The β2 adrenergic drugs are one of the most commonly used for this purpose. However it is known that they may cause tachycardia and may have substantial proarrhythmic effect. The investigators' aim is to estimate the influence of nebulized bronchodilatory drugs on selected electrophysiological parameters, whose changes are generally recognized as potentially increasing the risk of ventricular and supraventricular arrhythmias. Two drugs will be compared - salbutamol given in two doses and ipratropium bromide

Detailed description: 50 mechanically ventilated patients above 18 years of age and with presence of clinical features of bronchospasm requiring treatment with nebulised short-acting beta-2 mimetic.
  Participants will be randomly allocated into two equal groups: a group that was to receive the dose of 2.5 mg and a group that was to receive the dose of 5 mg of nebulised salbutamol. The duration of nebulisation will be set for 20 minutes and Holter ECG data are to be recorded for 60 minutes from the initiation of the nebuliser. The acquired Holter ECG data will be analysed at 10 time points: before salbutamol administration and 5, 10, 15, 20, 25, 30, 40, 50, and 60 minutes following initiation of nebulisation. Changes in QT interval, corrected QT intervals calculated using Bazett's correction and the Framingham formula and transmural dispersion of repolarization TDR will be assessed.

Eligibility: Inclusion Criteria:
  -  the necessity of b2 adrenergics an m2 mimetics administration
  Exclusion Criteria:
  -  patients with past medical history of ventricular arrhythmias ( ventricular tachycardia, ventricular fibril, Torsade de pointes)
  -  patients with persistent atrial fibrillation
  -  patients with abnormal plasma sodium, potassium, magnesium, and ionized calcium concentration

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C)

Summary: To understand if Mexiletine will restores normal colonic motility in a patient with irritable bowel syndrome - constipation (IBS-C) and a genetic mutation in SCN5A.

Detailed description: To understand if Mexiletine will restore normal colonic motility in a patient with a missense mutation in SCN5A, which encodes a voltage-sensitive sodium channel NaV1.5 as it is known to rescue certain expression defects of NaV1.5 in vitro.

Eligibility: Inclusion Criteria:
  -  Established IBS diagnosis with a known A997T mutation in NaV1.5T
  Exclusion Criteria:
  -  Normal 48-hour baseline transit study
  -  Current use of mexiletine
  -  Inability to stay in Rochester for 9 days for testing
  -  Known allergy to mexiletine
  -  Inability to complete daily diary
  -  Taking a medication known to affect myotonia, had a coexisting neuromuscular disease, or had another serious medical illness including second- or third-degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmia, history of cardiac arrhythmia requiring medication, congestive heart failure, symptomatic cardiomyopathy, or symptomatic coronary artery disease
  -  Inability to withdraw medications known to interact with mexiletine. Patient is currently not on any of these medications

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Long Term Prophylactic Therapy of Congenital Long QT Syndrome Type III (LQT3) With Ranolazine

Summary: The purpose of this study is to determine whether ranolazine will reduce the risk of arrhythmic events in patients with long QT syndrome type 3.


Eligibility: Inclusion Criteria:
  -  Long QT patients with genetic confirmation of carrier-status for the D1790G mutation in the SCN5A gene
  -  Corrected QT interval > 460 msec
  Exclusion Criteria:
  -  Need for therapy with medications that are potent or moderately potent CYP3A inhibitors (such as ketoconazole, diltiazem, verapamil, macrolide antibiotics or HIV protease inhibitors)

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Long-Term Study of IGIV, 10% in Alzheimer´s Disease

Summary: The purpose of this long-term study is to provide additional evidence of safety and efficacy of IGIV, 10% treatment in participants with Alzheimer´s Disease who have completed the Phase 3 Baxter precursor study 160701. All participants will receive IGIV, 10% at either 0.2 g/kg or 0.4 g/kg body weight depending on their treatment assignment in Baxter study 160701. Participants and investigators will be blinded to dose unless otherwise notified by the sponsor.


Eligibility: Main Inclusion Criteria:
  -  Completed 18 months of study treatment and assessments in Baxter precursor study 160701
  -  Diagnosis of probable Alzheimer´s Disease (AD)
  -  Able to comply with testing and infusion regimen (including adequate corrected visual acuity and hearing ability)
  -  Has a caregiver (study partner) who is willing and able to participate
  Main Exclusion Criteria:
  -  Significant neurological disease other than AD
  -  Clinically significant cardiac/cardiovascular problems (e.g. uncontrolled blood pressure, atrial fibrillation, heart disease, clotting disorders, strokes, or recent heart attack)
  -  Contraindication to undergoing MRI (e.g. pacemaker [with the exception of an MRI-compatible pacemaker], severe claustrophobia, ferromagnetic implants such as a metal plate)
  -  Specific findings on brain MRI (microhemorrhages, superficial siderosis, vasogenic edema, a macrohemorrhage, major stroke, or multiple lacunae)
  -  Active malignancy or history of malignancy within 5 years prior to screening with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment
  -  Uncontrolled major depression, psychosis, or other major psychiatric disorder(s)
  -  Poorly controlled diabetes
  -  Serious problems with liver or kidneys
  -  Known history of hypersensitivity following infusions of human blood or blood components (e.g. human immunoglobulins or human albumin)
  -  Current or recent treatment with immunomodulatory therapies (with the exception of immunoglobulin and non-systemic and low-dose systemic corticosteroids)
  -  Recent use of investigational drugs or biologics, including those aimed at altering AD progression (with the exception of immunoglobulin)
  -  Active immunization for the treatment of AD at any time
  There are reasons why it might not be appropriate to participate in this trial. Please contact Medical Information at medinfo@baxter.com for details.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Comparison Between Epinephrine and Exercise Test in QT Long Syndrome Patients

Summary: The aim of the study is to evaluate the best stress exam to unmask long QT in patient with KCNQ1 or KCNH2 mutation without long QT interval in rest electrocardiogram.

Detailed description: 65 patients with KCNQ1 or KCNH2 mutation presenting QTc interval <470msec and 65 patients without KCNQ1 or KCNH2 mutation presenting QTc interval <470msec will be included.
  All patients will have the 2 tests: exercise test and epinephrine test, in one half day.
  At the end of the inclusions, two experts will examine examens results without knowing in which arm (mutated or not) the patient belongs.

Eligibility: Inclusion Criteria:
  Patients with QTc<470 msec, and with molecular analysis (KCNQ1 or KCNH2 genes) performed in order to include 65 patients with KCNQ1 or KCNH2 mutation and 65 patients without KCNQ1 or KCNH2 mutation (controls).
  Exclusion Criteria:
  -  QTc interval >470msec
  -  Treatment interfering with cardiac repolarisation
  -  Under 15 years old
  -  Pregnant women
  -  Contraindication to exercise or epinephrine tests
  -  Patients without social coverage

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Pulmonary Vasculopathy Under Second-line Therapy of Chronic Myeloid Leukemia

Summary: Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder characterized by a translocation between chromosome 9 and 22, leading to a pathogenic tyrosine kinase signal transduction protein. CML can be treated with tyrosine kinase inhibitors (TKIs), which inhibit BCR/ABL kinase, such as imatinib. In about 20% of CML patients who are treated by imatinib, a complete cytogenetic response cannot be achieved. The other two novel TKIs (dasatinib and nilotinib), achieve higher rates of complete cytogenetic response and they are proposed as second-line therapy for imatinib-resistant patients or for those who do not tolerate imatinib. Dasatinib inhibits BCR/ABL kinase in about >300 times in vitro in more than imatinib and also inhibits several other kinases, including the Src family. Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. Imatinib and nilotinib do not inhibit the Src.
  Incident cases of precapillary PH have been reported in patients who have CML treated with the dasatinib. Improvements were usually observed after withdrawal of dasatinib.
  This study is designed to identify incident cases of dasatinib-associated PH and describe pulmonary vascular changes induced by dasatinib. As comparison population will be patients who receive another second-line TKI (nilotinib).

Detailed description: Doppler echocardiography at rest will be performed in each patient. Patients without exercise capacity limitation an exercise test (Doppler echocardiography with spiroergometry) will be performed. Patients who show elevated SPAP at rest or during exercise (in this study SPAP ≥ 40 mmHg) or with reduced exercise capacity (peak VO2 < 75%) a right heart catheterization (RHC) will be suggested. Additionally for the evaluation of exercise capacity a 6 MWD will be performed. This work- up of patients allows clinical and hemodynamic evaluation.

Eligibility: Inclusion Criteria:
  -  patients with chronic myeloid leukemia under second-line therapy with dasatinib or nilotinib
  -  written informed consent
  Exclusion Criteria:
  -  Manifest pulmonary hypertension
  -  significant pulmonary disease
  -  Left-sided heart failure or diastolic compliance dysfunction +
  -  Hemodynamic relevant valvular disease
  -  Systemic arterial hypertension (at rest systolic >150 mmHg, diastolic > 90 mmHg, during exercise > 220 mmHg)
  -  Severe anemia
  -  Uncontrolled supraventricular and ventricular arrhythmias
  -  Myocardial infarction (within the last 12 months)
  -  Pulmonary embolism (within the last 12 months)
  -  Recent therapy changes (within the last 12 months)
  -  Recent major surgeries (within the last 12 months)
  -  For exercise tests: musculoskeletal diseases which may unable the exercise tests.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Gene Therapy for Tay-Sachs Disease

Summary: Hypothesis: To study the natural history of Tay-Sachs disease and evaluate therapeutic interventions.
  This study is intended to work in collaboration with NCT00668187 "A Natural History Study of Hexosaminidase Deficiency." Because so few patients with Tay-Sachs disease present annually, we will maximize both research projects by enrolling patients in both studies. For this present study, we will perform retrospective medical record review to gather data. Through this medical record review, we will collect biomarker analysis results, neuroimaging report data, quality-of-life questionnaire data and ophthalmology exam findings. If the subject has undergone therapy or treatment, the results will be noted.

Detailed description: Much has been done in the past four decades to better understand, improve diagnostic measures of, and prevent hexosaminidase deficiency diseases, yet all of them — Tay-Sachs, Sandhoff, and Late Onset Tay-Sachs (LOTS) — remain diseases without treatment. Much work remains to be done to understand and effectively treat these diseases. To date, no comprehensive assessment of the natural history of Tay-Sachs or Sandhoff has been undertaken. The information that is gathered through this study will characterize and describe the Tay-Sachs disease population as a whole, including the variability and progression of this disease. This information, in turn, will function as a point of reference against which to assess the efficacy of therapeutic interventions. Therapeutic interventions may include any treatments/therapies the subject may have undergone in the past, including hematopoietic cell transplantation, and/or the administration of miglustat, acetylcysteine, or other pharmaceutical agents; and possible future gene therapies.

Eligibility: Inclusion Criteria:
  Any person who has been diagnosed with a hexosaminidase deficiency disease can be included in this study.
  Exclusion Criteria:
  The only exclusion criteria is a desire not to participate in this study.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: A Study to Explore the Routes of Elimination of MDV3100

Summary: A study to investigate the excretion routes of radio-labelled MDV3100.


Eligibility: Inclusion Criteria:
  -  Body Mass Index within 18.5 to 30.0kg/m2
  -  Regular defecation pattern (minimum once per 2 days).
  -  Subject must be non-fertile, i.e., surgically sterilized or must practice an adequate contraceptive method to prevent pregnancies as defined in the protocol.
  Exclusion Criteria:
  -  Known or suspected hypersensitivity to MDV3100, or any components of the formulation used.
  -  Any of the liver function tests above the upper limit of normal. A retest to confirm the result may be performed once.
  -  Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever).
  -  Abnormal pulse and/or blood pressure measurements at the pre-study visit as follows: Pulse <40 or >90 bpm; mean systolic blood pressure >140 mmHg ; mean diastolic blood pressure >90 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically).
  -  A QTc interval of > 430 ms after repeated measurements (consistently after duplicate measurements), a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS).
  -  Use of any prescribed or OTC (over-the-counter) drugs (including vitamins, natural and herbal remedies, e.g. St. John's wort) in the 2 weeks prior to admission to the Clinical Unit, except for occasional use of paracetamol (up to 3 g/day).
  -  Regular use of any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
  -  Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.
  -  Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)), during work or during participation in a clinical study in the previous year.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Worm Study: Modifier Genes in Sudden Cardiac Death

Summary: Quest for modifier genes associated with ventricular arrhythmias in presence of a cardiac sodium channel gene (SCN5A-delPhe1617) mutation.

Detailed description: In a large Dutch SCN5A founder population with malignant ventricular arrhythmias, the investigators aim to identify genetic modifiers by means of whole-exome sequencing and to establish a comprehensive genotype-phenotype correlation, focussing on clinical and cellular electrophysiological characteristics and neurocardiac modulation.

Eligibility: Inclusion Criteria (mutation carrier group):
  -  Age ≥ 18 years.
  -  Heterozygous or homozygous carriership of SCN5A-delPhe1617.
  -  Confirmed kinship to the founder population by haplotype analysis using predefined microsatellite markers.
  -  Written informed consent.
  Inclusion Criteria (non-mutation carrier group):
  -  Age ≥ 18 years.
  -  Non SCN5A-delPhe1617 genotype.
  -  Confirmed kinship to the Founder Group by haplotype analysis using predefined microsatellite marker.
  -  Written informed consent.
  Inclusion criteria Spouse Group
  -  Age ≥ 18 years.
  -  Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
  -  Written informed consent.
  Exclusion Criteria:
  -  Age ≥ 18 years.
  -  Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
  -  Written informed consent.

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: A Study of RG1662 in Adults and Adolescents With Down Syndrome (CLEMATIS)

Summary: This multi-center, randomized, double-blind, 3-arm, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RG1662 in adults and adolescents with Down syndrome. Subjects will be randomized to receive RG1662 either at low or high dose or placebo orally twice daily for 26 weeks.


Eligibility: Inclusion Criteria:
  -  Individuals aged 12-30 years of age inclusive
  -  Clinical diagnosis of Down syndrome (trisomy 21) confirmed by chromosomal analysis (karyotyping)
  -  Males, or non-pregnant, non-lactating females. For females of childbearing potential, strict contraceptive prevention is required.
  -  Body-mass Index (BMI) 18-42 and 15-30 kg/m2 inclusive for adults and adolescents respectively
  -  Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)-preschool 2 word classes task
  -  Subjects must have a parent, or other reliable caregiver who agrees to accompany the subject to all clinic visits, provide information about the subject as required by the protocol, and ensure compliance with the medication schedule
  -  Study participants must have sufficient language, vision and hearing to participate in study evaluations, as judged clinically by investigator
  Exclusion Criteria:
  -  Subjects with a current DSM 5 diagnosis of any primary psychiatric diagnosis (including ASD or MDD)
  -  Subjects with a history of infantile spasms, of West syndrome, Lennox-Gastaut syndrome, Early Infantile Epileptic Encephalopathy or any treatment-refractory epilepsy associated with cognitive or developmental regression, of severe head trauma or CNS infections (e.g. meningitis)
  -  Subjects with a known or suspected clinical seizure event of any type within 24 months prior to screening
  -  Clinically relevant ECG abnormalities at screening or baseline; QTcF above 450 ms; personal or family history (first degree relatives) of congenital long QT syndrome
  -  Inadequate renal or hepatic function

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: QT-prolongation in Psychiatric Hospitals

Summary: Observational study in 6 psychiatric hospitals in Flanders. Patients are included when a QT-prolonging drug is added to a medication profile that already contains a potential QT-prolonging drug. An ECG is taken before the administration of the new drug and a week after starting the new drug to investigate the change in duration of the QTc-interval. Risk factors for developing QT-prolongation and blood concentrations of potassium and creatinine are documented.


Eligibility: Inclusion Criteria:
  -  inpatient in one of the 6 participating psychiatric hospitals
  -  QT-prolonging drug in the medication profile and the doctor prescribes another QT-prolonging drug
  Exclusion Criteria:
  -  age < 18 year

Relevance to patient case: not relevant
Patient case: 19-year-old female with long QT syndrome; genetic feature: KCNH2

Clinical trial: Effect of AKB-6548 on Cardiac Repolarization Intervals in Healthy Volunteers

Summary: The main purpose of this study is to evaluate the effect of single oral therapeutic and supratherapeutic doses of AKB-6548 on the QT interval.


Eligibility: Key Inclusion Criteria:
  -  Healthy, non-smoking males or females, 18 and 55 years of age, inclusive
  -  BMI 18.0 and 32.0 kg/m2, inclusive
  -  non clinically significant 12-lead ECG
  -  heart rate of 45 to 90 beats per minute, inclusive
  -  mean systolic blood pressure <141 mmHg and mean diastolic blood pressure < 90 mmHg
  Key Exclusion Criteria:
  -  history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
  -  history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias, or torsades de pointes, structural heart disease, or a family history of Long QT syndrome
  -  significant abnormalities in liver function tests
  -  history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
  -  history of Gilbert's Syndrome
  -  positive hepatitis panel
  -  seizure disorder or receiving anti-epilepsy medication for seizure disorder
  -  any acute or chronic condition that, in the opinion of the Investigator, may pose a safety risk to a subject in this study or which would limit the subject's ability to complete and/or participate in this clinical study

Relevance to patient case: not relevant