35 Clinical Trials for Various Conditions
Part 1: This is a Phase 1b, randomized, double-blind, crossover, dose escalation, placebo-controlled study to evaluate the effect of oral LQT-1213 on dofetilide-induced QTc prolongation in healthy adult subjects. This is a 2-treatment, 2-period crossover study with approximately up to 28 healthy subjects, with screening procedures within 28 days of enrolment. Part 2: This is a Phase 2a, single-blind, placebo run-in, multiple-dose safety study to evaluate the safety, tolerability, and PK of LQT-1213 in patients diagnosed with LQT1, LQT2 or LQT3. Up to 12 participants with LQT1, up to 20 participants with LQT2 and up to 12 participants with LQT3 will be recruited.
The purpose of this study is to further develop and evaluate a diagnostic procedure suitable for use in an inexpensive diagnostic instrument suitable for screening for Long QT Syndrome (LQTS) in the primary care environment.
The goal of this study is to determine whether anti-Ro/SSA antibodies are associated with acquired QT prolongation in subjects with connective tissue disease. The investigators will investigate whether gender or race influence correlation between anti-Ro antibody status and prolonged QT interval and the role of inflammatory cytokines in association with anti-Ro antibodies and QT prolongation. The investigators propose to add an additional objective to test whether QT prolongation is reversible with moderate doses of prednisone in patients with QT interval greater than 500 msec.
Obstructive sleep apnea (OSA) has been associated with cardiac repolarization abnormalities and implicated in sudden cardiac death. A biologically plausible mechanism by which OSA exerts this lethality is by QT interval prolongation, a known marker of ventricular tachyarrhythmias (VTA) leading to cardiac death. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic disorder characterized by prolonged QT interval on the electrocardiogram and increased propensity for VTA. Preliminary data identify an association of the extent of severity of OSA and progressive prolongation of the corrected QT interval in LQTS.
The postnatal diagnosis of Long QT Syndrome (LQTS) is suggested by a prolonged QT interval on 12 lead electrocardiogram (ECG), strengthened by a positive family history and/or characteristic arrhythmias and confirmed by genetic testing. However, for several reasons such LQTS testing cannot be performed successfully before birth. First, fetal ECG is not possible and direct measure of the fetal QT interval by magnetocardiography is limited to fewer than 10 sites world-wide. Second, while genetic testing can be performed in utero, there is risk to the pregnancy and the fetus. Third, although some fetuses present with arrhythmias easily recognized as LQTS (torsade des pointes (TdP) and/or 2° atrioventricular (AV) block, this is uncommon, occurring in \<25% of fetal LQTS cases. Rather, the most common presentation of fetal LQTS is sinus bradycardia, a subtle rhythm disturbance that often is unappreciated to be abnormal. Consequently, the majority of LQTS cases are unsuspected and undiagnosed during fetal life, with dire consequences. For example, maternal medications commonly used during pregnancy can prolong the fetal QT interval and may provoke lethal fetal ventricular arrhythmias. But the most significant consequence is the missed opportunity for primary prevention of life threatening ventricular arrhythmias after birth because the infant is not suspected to have LQTS before birth. The over-arching goal of the study is to overcome the barriers to prenatal detection of LQTS. The investigators plan to do so by developing an algorithm using fetal heart rate (FHR) which will discriminate fetuses with or without LQTS. Immediate Goal: The investigators propose a multicenter pre-birth observational cohort study to develop a Fetal Heart Rate (FHR)/Gestational Age (GA) algorithm from a cohort of fetuses recruited from 13 national and international centers where one parent is known by prior genetic testing to have a mutation in one of the common LQTS genes: potassium voltage-gated channel subfamily Q member 1 (KCNQ1), potassium voltage-gated channel subfamily H member 2 (KCNH2), or sodium voltage-gated channel alpha subunit 5 (SCN5A). The investigators have chosen this population because 1) These mutations are the most common genetic causes of LQTS, and 2) Offspring will have high risk of LQTS as inheritance of these LQTS gene mutations is autosomal dominant. Thus, progeny of parents with a known mutation are at high (50%) risk of having the same parental LQTS mutation. The algorithm will be developed using FHR measured serially throughout pregnancy. All offspring will undergo postnatal genetic testing for the parental mutation as the gold standard for diagnosing the presence or absence of LQTS.
The purpose of this project is to test a new, very compact, 12-lead ECG device as a way to detect long QT syndrome (LQTS) in infants. The device -- called QTScreen -- was developed in Phase I of this project. In Phase II, the goals are to test the capacity of the device for LQTS screening in newborns and to obtain prevalence data on LQTS in California. The 4 main objectives are: 1. To validate the capacity of QTScreen for LQTS screening in newborns. 2. To determine the extent to which parents are able to use QTScreen on their babies at home. 3. To survey end-user experience and opinions. 4. To estimate the LQTS prevalence in California.
The primary objective of this study is to evaluate the effect of oral eleclazine on mean daytime QTcF interval after 24 weeks of treatment with elecalzine in participants with long QT syndrome Type 3. During the single-blind treatment period (24 weeks), participants will receive eleclazine and/or eleclazine placebo. Following the single-blind treatment period, participants who have not permanently discontinued study drug will be eligible, at the discretion of the investigator, to continue receiving eleclazine during an open-label extension (OLE) phase.
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.
To investigate the clinical, genetic and cardiologic aspects of the Long QT Syndrome, a predominantly hereditary disease with episodic malignant arrhythmias and sudden death, and a demonstrated gene linkage in a large pedigree.
This is a single-center, randomized, double-blind, placebo-controlled study to be conducted in 2 parts: single ascending dose (SAD) incorporating a food effect arm and multiple ascending dose (MAD). Potential participants for each part will undergo screening procedures within 28 days of enrollment.
An important aspect of successful genomic medicine implementation is developing effective approaches for screening at-risk family members after probands are identified, also known as cascade screening. Most cascade screening studies conducted to date have been conducted outside the US, and very few studies have used a rigorous approach involving a comparator group or randomized controlled design. A major question in the field is how to most effectively implement cascade screening, given commonly cited communication barriers, while respecting privacy among probands and family members. This study will conduct a randomized controlled trial to assess direct contact of relatives by study team members vs indirect, or proband-initiated, contact. We will assess efficacy of the cascade screening intervention, patient-centered outcomes regarding mental, physical, and psychosocial outcomes in probands and family members, and implementation evaluation outcomes. Individuals who are known to carry the KCNQ1 Met224Thr or APOB Arg3527Gln variant will be eligible to participate. After providing consent and being deemed eligible, individuals will be randomized in a 1:1 manner into the direct or indirect contact of family members arm of the study. The randomization will be stratified by variant to ensure equal representation of each variant in the study arms. Individuals in the indirect arm will be instructed to contact their first-degree family members about the opportunity to be screened. They will be provided with a disease-specific pamphlet and a family letter explaining the cascade screening. In the direct arm, probands will be advised that the study staff will be contacting their family members. They will be instructed to also contact their family members prior to the study team contacting them. Approximately two weeks after this meeting with the proband, the study staff will mail letters to eligible first-degree family members of the probands. If we do not hear back from individual family members, we will follow-up with another letter, telephone call, or home visit. The information contained in the letters will be the same information for both the direct and indirect arms of the study. All interested family members will receive pre-test counseling and free, in-home, saliva-based genetic testing, and post-test counseling.
This research will determine if: 1) Oral progesterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in postmenopausal women 50 years of age or older, and 2) Transdermal testosterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in men 65 years of age or older. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Men 65 years of age or older. Study 1: Each postmenopausal woman will take progesterone or placebo capsules for 1 week. After a 14-day "washout" (no progesterone or placebo) each subject will then take the alternative therapy (progesterone or placebo) for 1 week. After 7 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the progesterone and placebo phases will be compared. Study 2: Each man 65 years of age or older will apply transdermal testosterone or transdermal placebo gel for 3 days. After a 7-day "washout" (no testosterone or placebo) each subject will then apply the alternative therapy (testosterone or placebo gel) for 1 week. After 3 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the testosterone and placebo phases will be compared.
This research will determine if oral progesterone attenuates drug-induced QT interval lengthening in a) Postmenopausal women 50 years of age or older, and b) Premenopausal women studied during the ovulation phase of the menstrual cycle. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Premenopausal women. Each subject will take progesterone or placebo capsules for 1 week. After a two-week "washout" (no progesterone or placebo) each subject will then take the alternative therapy (progesterone or placebo) for 1 week. After 7 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the progesterone and placebo phases will be compared
The objectives of the protocol are to: (1) evaluate the uptake of cascade screening and preventative therapies after the implementation of a simplified screening process and (2) assess proband and family member perspectives about the return of research results and cascade screening for the KCNQ1 Thr224Met variant. The investigators will conduct a mixed methods study in the Old Order Amish community where the KCNQ1 variant is enriched over 100,000-fold compared to other populations. The intervention will offer free, mail-in, saliva-based genetic testing for family members of probands. The rate of uptake of testing and preventative therapy after the intervention is implemented (i.e. when 'simplified' free, mail-in, saliva-based testing was available) will be compared to data from before the intervention (i.e. when 'traditional' $50 blood-based testing was available to family members) when uptake was essentially zero. The primary outcome is the rate of uptake of cascade screening with the intervention ('simplified'). The secondary outcomes include: extent of disclosure of genotype results before and after the intervention, proportion of informed relatives who get screened before and after the intervention, and the uptake of appropriate preventative care (e.g. seeing a cardiologist and/or taking beta-blocker). The tertiary outcomes are demographic characteristics associated with uptake of cascade screening or uptake of preventative therapy. The investigators will also assess qualitative themes surrounding the return of results process and cascade screening using interviews.
Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. While TdP occurs more commonly in women, 33-45% of all cases of TdP have occurred in men. Older age is a risk factor for drug-induced TdP in men, possibly due to declining serum testosterone concentrations. Available evidence shows an inverse relationship between QTc intervals and serum testosterone concentrations. In addition, experimental data, including those from the investigators' laboratory, suggest that both exogenous testosterone or progesterone administration may be protective against prolongation of ventricular repolarization and TdP. Specific Aim: Establish the influence of transdermal testosterone administration and oral progesterone administration as preventive methods by which to diminish the degree of drug-induced QT interval prolongation in men 65 years of age or older. Hypothesis: Transdermal testosterone administration and oral progesterone administration both effectively attenuate drug-induced QT interval response in older men. To test this hypothesis, transdermal testosterone, oral progesterone or placebo will be administered in a 3-way crossover study to men 65 years of age or older. QTc interval response to low-dose ibutilide will be assessed. The primary endpoints will be Fridericia-corrected QT interval (QTF) response to ibutilide, in the presence and absence of testosterone, and in the presence or absence of progesterone: 1) Effect on pre-ibutilide QTF, 2) Effect on maximum post-ibutilide QTF, 3) Effect on % change in post-ibutilide QTF, and 2) Area under the QTF interval-time curves.
This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of eleclazine and its metabolite, GS-623134, in participants with normal and impaired renal function. Participants in the healthy control group will be matched to participants with impaired renal function by age (± 5 years), gender, and body mass index (± 10%).
To assess the ability of common genetic variants in aggregate to predict drug-induced QT prolongation in patients being loaded with dofetilide or sotalol.
This is a registry to examine genetic and clinical predictors of torsade de pointes events.
The primary objective of this study is to evaluate the pharmacokinetic (PK) profile of oral eleclazine and its metabolite, GS-623134, in participants with normal and impaired hepatic function. Participants in the healthy control group will be matched to participants with impaired hepatic function by age (± 5 years), gender, and body mass index (± 10%).
This study will evaluate the effect of oral GS-6615 on QTc interval in healthy adults with dofetilide-induced QTc prolongation.
This mechanism of action study is to evaluate the effect of oral GS-6615 on the QTc interval in participants with Long QT-3 syndrome. This study will be performed in six cohorts of participants in a sequential manner, four single-dose cohorts followed by two multiple-dose cohorts. Duration of treatment for the single-dose cohorts and multiple-dose cohorts will be 1 day and 7 days, respectively. Participants will be confined at the study center from check-in until completion of assessments at discharge. Participants will be continuously monitored using real-time telemetry throughout the in-clinic confinement. Physical examinations including vital signs, laboratory analysis, electrocardiograms (ECGs), Holter recordings and echocardiography (ECHO) will be performed at defined time points throughout the study period. Assessment of adverse events and concomitant medications will continue throughout the duration of the study.
The purpose of this study is to determine whether late sodium channel blockade might be effective in shortening the QTc interval in various LQT3 mutations and be considered as a safe therapeutic option for LQT3 patients.
The purpose of this study is to validate the continuous patch monitoring system to evaluate cardiac arrhythmias in patients receiving drugs that can cause cardiac complications and compare the continuous patch system with standard electrocardiograms (ECGs).
Each year world-wide, 2.5 million fetuses die unexpectedly in the last half of pregnancy, 25,000 in the United States, making fetal demise ten-times more common than Sudden Infant Death Syndrome. This study will apply a novel type of non-invasive monitoring, called fetal magnetocardiography (fMCG) used thus far to successfully evaluate fetal arrhythmias, in order to discover potential hidden electrophysiologic abnormalities that could lead to fetal demise in five high-risk pregnancy conditions associated with fetal demise.
The goal is to determine how lifestyle and exercise impact the well-being of individuals with hypertrophic cardiomyopathy (HCM) and long QT syndrome (LQTS). Ancillary study Aim: To understand how the coronavirus epidemic is impacting psychological health and quality of life in the LIVE population
Human induced pluripotent stem cells (hiPSCs) have driven a paradigm shift in the modeling of human disease; the ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability, with applications in personalized predictive pharmacology/toxicology, cell therapy and regenerative medicine. This research will collect blood or skin biopsies from patients and healthy controls for the purpose of generating cell and tissue models of Mendelian heritable forms of heart disease focusing on cardiomyopathies, channelopathies and neuromuscular diseases. Cardiomyocytes derived from hiPSCs will provide a ready source of disease specific cells to study pathogenesis and therapeutics.
The purpose of this study is to determine the true incidence of long QT (LQT) amongst a large cohort of subjects diagnosed with unilateral (right/left) or bilateral sensorineural hearing loss.
Fetal research and clinical practice has been hampered by a lack of suitable investigational techniques. Currently, ultrasound is the only widely used method of studying fetal anatomy and physiology, but it has significant limitations for assessment of cardiac rhythm. The proposed study will allow us to investigate fetal magnetocardiography (fMCG) as a new tool for the study of normal and abnormal fetal heart rate and rhythm, with a goal of demonstrating probable benefit from use of the device in patients with serious fetal arrhythmia. We propose a study that will last 1-2 years and will provide data to aid in assessing the safety and effectiveness of fMCG for diagnosis and management of patients with abnormal fetal heart rate and rhythm. We hope that the data from the study will support a Humanitarian Device Exemption (HDE) application for the subject device. The safety and efficacy study designs are described below. High-risk subjects will undergo echocardiography as part of their routine clinical management, and our results will be compared to the echocardiography results, as well as with postnatal ECG, when available. (Since many arrhythmias resolve prior to birth, either due to resolution of disease or due to treatment, only a limited number of diseases allow postnatal comparison). For rhythms that persist after birth, the diagnostic utility of fMCG and echocardiography will be assessed by computing the sensitivity (Sn) and specificity (Sp) relative to postnatal ECG for the following prenatal modalities: (i) the fMCG, (ii) the original (referral) echo, (iii) if available, the in-lab echocardiogram at the time of the fMCG study. Secondary endpoints will assess changes in diagnosis and in clinical management due to the additional information provided by fMCG, compared to the information provided by echocardiography alone.
This is a randomized, prospective clinical trial comparing 2 different types of implantable cardioverter defibrillator (ICD) leads in children and patients with congenital heart disease. ICD lead survival in this patient group is particularly suboptimal, and lead extraction is technically difficult and carries a substantial morbidity risk. Recently, improved ICD lead designs have been released and are currently being utilized in patients. The main aim of the study is to determine if either type of lead performs better in terms of implantation electrical characteristics, long-term survival without breaking, and ease of extractability.
To assess the effect of ERB-041 after multiple oral doses on cardiac repolarization as assessed by the QTc interval.