Screening effects of HCN channel blockers on sleep/wake behavior in zebrafish.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food and Drug Administration (FDA) as a medication to lower heart rate by blocking hyperpolarization activated inward current in the sinoatrial node. In addition, a growing body of evidence suggests a role for HCN channels in regulation of sleep/wake behavior.

Corrigendum: Case report: A patient with Delayed Sleep-Wake Phase Disorder and Optic Nerve Hypoplasia treated with tasimelteon: a case study.

[This corrects the article DOI: 10.3389/fnins.2023.

The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial.

Background: Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.

Methods: A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks.

Efficacy and Safety of Iloperidone in Bipolar Mania: A Double-Blind, Placebo-Controlled Study.

To determine if iloperidone, a second-generation antipsychotic, reduces symptoms of bipolar mania. This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults with bipolar mania at 27 US and international sites between April 2021 and September 2022. Participants were randomized 1:1 to iloperidone (up to 24 mg/d given twice daily) or placebo for 4 weeks.

Case report: A patient with Delayed Sleep-Wake Phase Disorder and Optic Nerve Hypoplasia treated with tasimelteon: a case study.

Unlabelled: We present a case of an adult female diagnosed with Delayed Sleep-Wake Phase Disorder (DSWPD) and Optic Nerve Hypoplasia (ONH), with a confirmed delayed Dim Light Melatonin Onset (DLMO), who reports the inability to fall asleep at their desired bedtime and obtain adequate sleep nightly, despite the ability to have a full night's sleep when not required to be up at a specific time for societal requirements. The participant was enrolled in an 11-month Open-Label Extension (OLE) following the randomized portion of a clinical study and was successfully treated with tasimelteon. DSWPD symptoms were resolved, and their previously delayed sleep-wake cycle was advanced.

Case report: A novel missense variant in melanopsin associates with delayed sleep phenotype: Whole genome sequencing study.

Melanopsin (OPN4) is a blue light-sensitive opsin-type G-protein coupled receptor. It is highly expressed in photosensitive retinal ganglion cells which mediate responses to light, including regulation of sleep, circadian photoentrainment, and pupillary light response. Mutations in were shown to affect responses to light, ultimately affecting the regulation of circadian rhythms and sleep.

Once-daily tasimelteon (VEC-162) for jet lag following transmeridian travel: A multicenter, randomized, double-blind, placebo-controlled trial.

Jet Lag Disorder is a Circadian Rhythm Sleep-Wake Disorder resulting from a misalignment of the endogenous circadian clock and the sleep and wake pattern required by a change in time zone. Jet lag is most severe following eastward travel. This multicenter, randomized, placebo-controlled clinical trial (JET) assessed the physiological mechanism of jet lag induced by a real-life transmeridian flight and evaluated the efficacy of tasimelteon-a circadian regulator acting as a dual melatonin receptor agonist, in the treatment of Jet Lag Disorder (JLD).

Enrichment of Patients With Ehlers Danlos Syndrome in Idiopathic Gastroparesis-A Gene Set Enrichment Analysis.

Introduction: Ehlers Danlos syndrome (EDS) is a heritable disorder of the connective tissue usually inherited as an autosomal dominant trait. We observe an enrichment of EDS cases in a gastroparesis clinical study.

Methods: We explored the frequency of EDS cases in 2 consecutive gastroparesis clinical studies.

Identification of potential COVID-19 treatment compounds which inhibit SARS Cov2 prototypic, Delta and Omicron variant infection.

Recurrent waves of COVID19 remain a major global health concern. Repurposing either FDA-approved or clinically advanced drug candidates can save time and effort required for validating the safety profile and FDA approval. However, the selection of appropriate screening approaches is key to identifying novel candidate drugs with a higher probability of clinical success.

Enrichment of Motilin Receptor Loss-of-Function Variants in Gastroparesis.

Introduction: Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain.

Methods: To ascertain the genetic risk factors for gastroparesis, we conducted the largest thus far whole-genome sequencing study of gastroparesis. We investigated the frequency and effect of rare loss-of-function variants in patients with both idiopathic and diabetic gastroparesis enrolled in a clinical study of gastroparesis.

Elevated plasma levels of CXCL16 in severe COVID-19 patients.

Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as the strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order the determine its role, we measured plasma levels of Chemokine (C-X-C motif) ligand 16 (CXCL16) in the plasma of COVID-19 hospitalized patients.

Tasimelteon safely and effectively improves sleep in Smith-Magenis syndrome: a double-blind randomized trial followed by an open-label extension.

Purpose: To assess the efficacy of tasimelteon to improve sleep in Smith-Magenis syndrome (SMS).

Methods: A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study.

Simulated driving performance in healthy adults after night-time administration of 20 mg tasimelteon.

An impairment in next day driving performance has been reported for almost every drug currently United States Food and Drug Administration (FDA) approved for improvement of sleep in chronic and transient insomnia. Tasimelteon, a melatonin receptor agonist, demonstrated significant improvements in night-time sleep, daytime naps, and sleep timing in non-24-hr sleep-wake disorder (Non-24) by entraining these patients to a 24-hr day as measured by melatonin and cortisol rhythms. Given this new mechanism of action of entraining the biological clock, we conducted a study to evaluate the potential effect tasimelteon may have on the ability to operate a motor vehicle.

Tradipitant in the Treatment of Motion Sickness: A Randomized, Double-Blind, Placebo-Controlled Study.

Novel therapies are needed for the treatment of motion sickness given the inadequate relief and bothersome and dangerous adverse effects of currently approved therapies. Neurokinin-1 (NK1) receptor antagonists have the potential to be effective in improving the symptoms of motion sickness, given the involvement of Substance P in nauseogenic and emetic pathways and the expression of NK1 receptors in the gastrointestinal system. Here we evaluated the efficacy of tradipitant, a novel NK1 receptor antagonist, in preventing motion sickness in variable sea conditions.

Efficacy of Tasimelteon (HETLIOZ®) in the Treatment of Jet Lag Disorder Evaluated in an 8-h Phase Advance Model; a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Most travelers experience Jet Lag Disorder (JLD) symptoms due to misalignment of their circadian rhythms with respect to the new time zone. We assessed the efficacy and safety of tasimelteon (HETLIOZ®) in healthy participants using a laboratory model of JLD induced by an 8-h phase advance of the sleep-wake cycle (JET8 Study). We hypothesized that tasimelteon treatment in participants experiencing JLD would cause increased sleep time, increased next-day alertness, and reduced next-day sleepiness.

Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial.

Background & Aims: Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis.

Methods: We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018.

Delayed sleep phase disorder risk is associated with absenteeism and impaired functioning.

Study Objectives: The absence of a screening questionnaire for delayed sleep phase disorder (DSPD) remains a barrier to its detection and subsequent clinical evaluation. We developed a questionnaire to screen for DSPD risk and assessed its impact on self-reported absenteeism and functioning in work/school, social, and family life.

Design: Cross-sectional, with 13,844 individuals responding to a survey through an Internet survey provider, from which 1315 completed surveys were obtained from eligible participants.

Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.

Background: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time.

Methods: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies.