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Background ALZ-801 is an orally available, valine-conjugated prodrug of tramiprosate. Tramiprosate, the active agent, is a small-molecule β-amyloid (Aβ) anti-oligomer and aggregation inhibitor that was evaluated extensively in preclinical and clinical investigations for the treatment of Alzheimer’s disease (AD). Tramiprosate has been found to inhibit β-amyloid oligomer formation by a multi-ligand enveloping mechanism of action that stabilizes Aβ42 monomers, resulting in the inhibition of formation of oligomers and subsequent aggregation. Although promising as an AD treatment, tramiprosate exhibited two limiting deficiencies: high intersubject pharmacokinetic (PK) variability likely due to extensive gastrointestinal metabolism, and mild-to-moderate incidence of nausea and vomiting. To address these, we developed an optimized prodrug, ALZ-801, which retains the favorable efficacy attributes of tramiprosate while improving oral PK variability and gastrointestinal tolerability. In this study, we summarize the phase I bridging program to evaluate the safety, tolerability and PK for ALZ-801 after single and multiple rising dose administration in healthy volunteers. Methods Randomized, placebo-controlled, phase I studies in 127 healthy male and female adult and elderly volunteers included [ 1 ] a single ascending dose (SAD) study; [ 2 ] a 14-day multiple ascending dose (MAD) study; and [ 3 ] a single-dose tablet food-effect study. This program was conducted with both a loose-filled capsule and an immediate-release tablet formulation, under both fasted and fed conditions. Safety and tolerability were assessed, and plasma and urine were collected for liquid chromatography-mass spectrometry (LC-MS) determination and non-compartmental PK analysis. In addition, we defined the target dose of ALZ-801 that delivers a steady-state plasma area under the curve (AUC) exposure of tramiprosate equivalent to that studied in the tramiprosate phase III study. Results ALZ-801 was well tolerated and there were no severe or serious adverse events (AEs) or laboratory findings. The most common AEs were transient mild nausea and some instances of vomiting, which were not dose-related and showed development of tolerance after continued use. ALZ-801 produced dose-dependent maximum plasma concentration ( C max ) and AUC exposures of tramiprosate, which were equivalent to that after oral tramiprosate, but with a substantially reduced intersubject variability and a longer elimination half-life. Administration of ALZ-801 with food markedly reduced the incidence of gastrointestinal symptoms compared with the fasted state, without affecting plasma tramiprosate exposure. An immediate-release tablet formulation of ALZ-801 displayed plasma exposure and low variability similar to the loose-filled capsule. ALZ-801 also showed excellent dose-proportionality without accumulation or decrease in plasma exposure of tramiprosate over 14 days. Based on these data, 265 mg of ALZ-801 twice daily was found to achieve a steady-state AUC exposure of tramiprosate equivalent to 150 mg twice daily of oral tramiprosate in the previous phase III trials. Conclusions ALZ-801, when administered in capsule and tablet forms, showed excellent oral safety and tolerability in healthy adults and elderly volunteers, with significantly improved PK characteristics over oral tramiprosate. A clinical dose of ALZ-801 (265 mg twice daily) was established that achieves the AUC exposure of 150 mg of tramiprosate twice daily, which showed positive cognitive and functional improvements in apolipoprotein E4/4 homozygous AD patients. These bridging data support the phase III development of ALZ-801in patients with AD.

The aim of the present study was to evaluate the effects of supplementation with a fixed combination of citicoline 500 mg, homotaurine 50 mg, and vitamin E 12 mg (CIT/HOMO/VITE) on contrast sensitivity and visual-related quality of life in patients with primary open-angle glaucoma (POAG) in mild stage. This was a multicenter, observational, cross-over, short-term, pilot study on POAG patients with stable controlled intraocular pressure (IOP). Patients were randomly assigned to Group 1 (current topical therapy for 4 months and then current topical therapy plus CIT/HOMO/VITE for 4 months) or Group 2 (CIT/HOMO/VITE in addition to current topical therapy for 4 months and then topical therapy alone for 4 months). Best-corrected visual acuity, IOP, visual field, and the Spaeth/Richman contrast sensitivity (SPARCS) test score were recorded at baseline and after 4 and 8 months. The Glaucoma Quality of Life-15 (GQL-15) questionnaire was administered at each check time. Forty-four patients were assigned to Group 1 and 65 to Group 2. Over the follow-up period, there were no significant changes in IOP or visual field findings, whereas SPARCS and GQL-15 findings significantly varied from baseline, both being improved in subjects treated with CIT/HOMO/VITE fixed combination. These results demonstrate that a daily intake of a fixed combination of citicoline, homotaurine, and vitamin E in addition to the topical medical treatment significantly increased the total score of the contrast sensitivity test and the quality of life in patients with POAG.

The impact of hypoxic repetitive sprint training on the overall performance of team sports remains controversial due to the specific nature of the exercise capacity required for team sports. While taurine and caffeine are widely utilized as supplements for repetitive sprint exercise in normoxic environments, their efficacy in hypoxic environments remains to be fully understood. Therefore, additional research is needed to explore the role of supplementation in hypoxic conditions. This study was to investigate the effects of caffeine (C), taurine (T), caffeine, and taurine co-ingestion (TC) or placebo (P) on repetitive sprint exercise performance and related physiological responses after exhaustion exercise in team athletes under simulated hypoxic conditions. A double-blind crossover randomized controlled experimental design was employed. 16 male participants (Age:23.69 ± 2.15 years, Body mass: 75.04 ± 7.79 kg, Height:1.78 ± 0.06 m) volunteered to receive four different supplement ingestions to complete the exercise tests: (1) placebo (5 mg/kg maltodextrin), (2) taurine (50 mg/kg), (3) caffeine (5 mg/kg), (4) taurine + caffeine (50 mg/kg + 5 mg/kg). All selected participants were university football players who had undergone rigorous training regimens (85–95% of maximum heart rate, duration of 60 min, with more than five training sessions per week). All participants completed an exhaustion test and subsequent repetitive sprint exercise in a simulated hypoxic environment (A simulation of a soccer game in sports mode). Time to exhaustion (TTE), peak power (PP), and mean power (MP) were recorded at the end of the exhaustion test and during the repetitive sprint exercise, respectively. This study designed an exercise protocol for repetitive sprinting after exhaustion exercise based on the pattern of play in football. The following variables were monitored throughout the experiments: heart rate (HR), blood lactate (B[La]), arterial oxygen saturation (SpO2), dyspnea, and rating of perceived exhaustion (RPE). The Stroop Test was administered at three separate time points: pre-test, mid-test, and post-test, throughout the exercise trial. The countermovement jump test (CMJ) was carried out at three specific time points: before the test, 3 min after the test, and 6 min after the test. The caffeine (C:618.56 + 42.50 s, p = 0.027, d = 0.996) and taurine + caffeine (TC: 613.69 + 37.74 s, p = 0.041, d = 0.902) groups significantly improved time to exhaustion compared to the placebo group. Blood lactate was significantly higher in the taurine + caffeine group than in the placebo group after repetitive sprint exercise (P: 9.87 ± 1.97, TC: 12.31 ± 2.54, p = 0.016). The caffeine group significantly reduced dyspnea, and rating of perceived exhaustion after repetitive sprint exercise (p < 0.05). The taurine (T: 43.42 ± 3.46, p = 0.005), caffeine (C: 44.11 ± 4.72, p < 0.001), and taurine + caffeine (TC: 43.04 ± 3.30, p = 0.011) groups all showed an increase in pre-exercise countermovement jump height. The caffeine group significantly reduced the consistent response time (p = 0.023) and inconsistent response time (p < 0.001) in the Stroop Test compared to the placebo group. Caffeine, along with combined taurine, significantly prolonged the duration of exhaustion exercise in a hypoxic environment; however, it did not affect subsequent repetitive sprint performance. Additionally, caffeine supplementation had a positive impact on cognitive performance during hypoxic training.

Background and aims Central venous catheters (CVCs) are essential for drug delivery in pediatric oncology patients but are associated with complications such as infection and thrombosis. This study aimed to compare the effects of taurolidine–citrate and unfractionated heparin lock solutions on catheter function, infection and thrombosis rates, and inflammatory markers in children with malignancies. Methods In this randomized, controlled trial, 76 pediatric oncology patients were allocated to receive either TauroLock ™ -HEP500 (containing taurolidine, 4% citrate, and 500 IU/mL heparin) or standard unfractionated heparin as the catheter lock solution. Patients were followed for 6 months. Laboratory evaluations, including complete blood count (CBC), high-sensitivity C -reactive protein (hs-CRP), and interleukin-6 (IL-6), were performed at baseline, 1 month, and 6 months, or upon clinical suspicion of infection. Results At 6 months, hs-CRP levels were significantly lower in the taurolidine–citrate group (2.1 ± 0.2 vs. 5.5 ± 2.2, p  = 0.001), as was total WBC count (3792.1 ± 325.3 vs. 4994.5 ± 462.1, p  = 0.028). IL-6 levels showed no statistically significant difference (9.2 ± 1.9 vs. 14.0 ± 3.1, p  = 0.067). The incidence of catheter-related infections (HR 3.55, 95% CI 0.68–18.4, p  = 0.460) and thrombosis (HR 4.13, 95% CI 0.43–39.91, p  = 0.221) did not differ significantly between groups. Conclusion Taurolidine–citrate exhibited a modest anti-inflammatory effect, reflected by reduced hs-CRP and WBC levels, without significant improvement in catheter-related complications or IL-6. The lack of major clinical benefit may relate to the heterogeneous and immunocompromised nature of pediatric oncology patients. Larger, adequately powered studies are warranted to clarify the long-term efficacy and safety of taurolidine–citrate in this population. Clinical Trials as IRCT20201107049296N4.

Background ASD is the most common neurodevelopment dysfunction and disabling disorder in childhood, with a lack of specific clinical treatment methods. Evidence-based study reveals that nutrients supplement can improve the core symptom of ASD. Our previous study demonstrated the children with ASD were found to have lower taurine levels in serum and urine samples. However, whether or not the taurine supplementation can improve the core symptom of ASD is unclear. Methods This is an exploratory randomized, double-blind, placebo-controlled trial. Sixty children with ASD will be randomly allocated to receive daily taurine supplementation (taking orally with the recommended dose) or placebo in a 1:1 ratio for 3 months. All children will receive behavioral treatment throughout the study period. All researchers, participants and their caregivers will be blinded until the completion of data analysis, and randomization and allocation will be fully concealed from all mentioned parties. Follow-up will be conducted at the baseline, 1st month, 2nd month, 3rd month, 6th month, 9th month and 12th month. The primary outcomes will focus on changes in scores of ASD-specific questionnaires. Discussion To our knowledge there are no randomized controlled trials assessing the effects of daily taurine supplementation on the core symptoms of ASD. This trial would help evaluate the efficacy of taurine supplementation on ASD, and initially explore if its potential value on clinical application outweighs the risk. Trial registrations ClinicalTrials Registry NCT05980520. Registered on July 31, 2023.

PurposeTo determine the effect of taurine supplementation on sweating and core temperature responses, including the transition from compensable to uncompensable heat stress, during prolonged low-intensity exercise of a fixed-heat production (~ 200W/m2) in hot conditions (37.5 °C), at both fixed and incremental vapour-pressure.MethodsFifteen females (n = 3) and males (n = 12; 27 ± 5 years, 78 ± 9 kg, V˙O2max 50.3 ± 7.8 mL/kg/min), completed a treadmill walking protocol (~ 200W/m2 heat production [Ḣprod]) in the heat (37.5 ± 0.1 °C) at fixed-(16-mmHg) and ramped-humidity (∆1.5-mmHg/5-min) following 1 week of oral taurine supplementation (50 mg/kg/bm) or placebo, in a double-blind, randomised, cross-over design. Participants were assessed for whole-body sweat loss (WBSL), local sweat rate (LSR), sweat gland activation (SGA), core temperature (Tcore), breakpoint of compensability (Pcrit) and calorimetric heat transfer components. Plasma volume and plasma taurine concentrations were established through pre- and post-trial blood samples.ResultsTaurine supplementation increased WBSL by 26.6% and 5.1% (p = 0.035), LSR by 15.5% and 7.8% (p = 0.013), SGA (1 × 1 cm) by 32.2% and 29.9% (p < 0.001) and SGA (3 × 3 cm) by 22.1% and 17.1% (p = 0.015) during the fixed- and ramped-humidity exercise periods, respectively. Evaporative heat loss was enhanced by 27% (p = 0.010), heat-storage reduced by 72% (p = 0.024) and Pcrit was greater in taurine vs placebo (25.0-mmHg vs 21.7-mmHg; p = 0.002).ConclusionTaurine supplementation increased sweating responses during fixed Ḣprod in hot conditions, prior to substantial heat strain and before the breakpoint of compensability, demonstrating improved thermoregulatory capacity. The enhanced evaporative cooling and reduced heat-storage delayed the subsequent upward inflection in Tcore—represented by a greater Pcrit—and offers a potential dietary supplementation strategy to support thermoregulation.

This study investigated the effects of acute oral taurine ingestion on: (1) the power–time relationship using the 3-min all-out test (3MAOT); (2) time to exhaustion (TTE) 5% > critical power (CP) and (3) the estimated time to complete (Tlim) a range of fixed target intensities. Twelve males completed a baseline 3MAOT test on a cycle ergometer. Following this, a double-blind, randomised cross-over design was followed, where participants were allocated to one of four conditions, separated by 72 h: TTE + taurine; TTE + placebo; 3MAOT + taurine; 3MAOT + placebo. Taurine was provided at 50 mg kg−1, whilst the placebo was 3 mg kg−1 maltodextrin. CP was higher (P < 0.05) in taurine (212 ± 36 W) than baseline (197 ± 40 W) and placebo (193 ± 35 W). Work end power was not affected by supplement (P > 0.05), yet TTE 5% > CP increased (P < 0.05) by 1.7 min after taurine (17.7 min) compared to placebo (16.0 min) and there were higher (P < 0.001) estimated Tlim across all work targets. Acute supplementation of 50 mg kg−1 of taurine improved CP and estimated performance at a range of severe work intensities. Oral taurine can be taken prior to exercise to enhance endurance performance.

Caffeine and taurine are commonly co‐ingested pre‐exercise but elicit different thermoregulatory responses; however, their combined effect on thermoregulation is unknown. Therefore, we evaluated the effects of oral caffeine and taurine co‐ingestion on time to exhaustion (TTE) and thermoregulatory responses to cycling in the heat at the gas exchange threshold (GET). Ten healthy nonheat acclimated participants took part in a double‐blind crossover study, completing a TTE in the heat (35°C; 40% relative humidity), cycling at a power output associated with the GET and 1 h after ingesting: caffeine (5 mg/kg) and taurine (50 mg/kg) combined or placebo. Pulmonary gas exchange, core and mean skin temperatures and whole‐body sweat rate (WBSR) were recorded throughout. Heat production was determined using partitional calorimetry. There were no differences in TTE between conditions (p = 0.608); however, the rate of oxygen consumption (p = 0.017), minute ventilation (p = 0.029) and heat production (p = 0.019) were higher following the supplement. There were no differences between conditions for skin (p = 0.539) and core temperature (p = 0.699), mean skin blood flow (p = 0.119), respiratory exchange ratio (p = 0.546) and WBSR (p = 0.897). Pre‐exercise co‐ingestion of caffeine and taurine in the heat had no ergogenic effect despite increasing the ventilatory and metabolic demand. Collectively, these data indicate minimal effects on whole‐body thermoregulation. Summary Pre‐exercise co‐ingestion of caffeine (5 mg/kg) and taurine (50 mg/kg) did not improve exercise tolerance in the heat vs. the placebo condition. There was an increased ventilatory and metabolic demand after supplementation but this did not translate to a change in core temperature during exercise. Taurine's established vascular effects may have been sufficient to supress the anticipated caffeine‐induced increases in core temperature. Further research is needed to clarify how metabolic heat gain was suppressed in the caffeine–taurine condition, which may characterise the role of taurine as part of a multiingredient pre‐exercise supplement in heat environments.

Based on the fact that taurine can increase lipid metabolism, the objective of the present study was to evaluate the effects of different doses of acute taurine supplementation on lipid oxidation levels in healthy young men after a single bout of fasting aerobic exercise. A double-blind, acute, and crossover study design was conducted. Seventeen men (age 24.8 ± 4.07y; BMI: 23.9 ± 2.57 kg/m²) participated in the present study. Different doses of taurine (TAU) (3 g or 6 g) or placebo were supplemented 90 min before a single bout of fasting aerobic exercise (on a treadmill at 60% of VO2 max). The subjects performed three trials, and each one was separated by seven days. Blood samples were collected at baseline and after the exercise protocol of each test to analyze plasma levels of glycerol and taurine. Lipid and carbohydrate oxidation were determined immediately after exercise for 15 min by indirect calorimetry. We observed that TAU supplementation (6 g) increased lipid oxidation (38%) and reduced the respiratory coefficient (4%) when compared to the placebo (p < 0.05). However, no differences in lipid oxidation were observed between the different doses of taurine (3 g and 6 g). For glycerol concentrations, there were no differences between trials. Six grams of TAU supplementation 90 min before a single bout of aerobic exercise in a fasted state was sufficient to increase the lipid oxidation post-exercise in healthy young men.

Background Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. Methods We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. Results A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo ( p  = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group ( p  = 0.27). Surgical site infection was reduced in the Taurolidine treated group ( p  = 0.09). Conclusion Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. Trial registration The trial was registered with EudraCT (year = 2008, registration number =  005570–12 ) and ISRCTN (year = 2008, registration number =  77,829,558 ).