Double-blind Placebo-controlled Study Research Articles

A Randomized Double-Blind Placebo-Controlled Study on the Safety and Efficacy of Probiotics for Insulin Resistance and Oxidative Stress Markers in Diabetic Patients With End-Stage Renal Disease on Hemodialysis

A Randomized Double-Blind Placebo-Controlled Study on the Safety and Efficacy of Probiotics for Insulin Resistance and Oxidative Stress Markers in Diabetic Patients With End-Stage Renal Disease on Hemodialysis

The effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cholinergic neural networks in humans: A neurophysiological study

ObjectiveThe mechanisms of actions of transcutaneous auricular vagus nerve stimulation (taVNS) are still unclear, however the activity of the cholinergic system seems to be critical for the induction of VNS-mediated plasticity. Transcranial Magnetic Stimulation (TMS) is a well-suited, non-invasive tool to investigate cortical microcircuits involving different neurotransmitters. Herein, we evaluated the effect of taVNS on short-latency afferent inhibition (SAI), a TMS paradigm specifically measuring cholinergic neurotransmission. MethodsFifteen healthy subjects participated in this randomized placebo-controlled double-blind study. Each subject underwent two different sessions of 1-hour exposure to taVNS (real and sham) separated by a minimum of 48 h. Real taVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe. We evaluated SAI bilaterally over the motor cortex before and after exposure to taVNS. ResultsNo side effects were reported by any of the participants.Statistical analysis did not show any significant effect of taVNS on SAI. ConclusionsOur study demonstrated that cholinergic circuits explored by SAI are different from circuits engaged by taVNS. SignificanceSince the influence of VNS on cholinergic neurotransmission has been exhaustively demonstrated in animal models, further studies are mandatory to understand the actual impact of VNS on cholinergic circuits in humans.

Results of the ACTION-Galactosemia Kids Study to Evaluate the Effects of Govorestat in Pediatric Patients with Classic Galactosemia.

To evaluate the pharmacodynamic effects and clinical outcomes of orally administered once-daily govorestat (AT-007), a central nervous system penetrant aldose reductase inhibitor, the double-blind placebo-controlled ACTION-Galactosemia Kids study (NCT04902781) randomly assigned 47 participants (2-17 years old) with Classic Galactosemia to 18 months of govorestat or placebo (2:1) treatment. Mean change in galactitol was compared between the treatment groups at each post-baseline timepoint using a t-test, with a mixed model for repeated measures (MMRM) analysis as a sensitivity analysis. Changes from baseline in clinical outcomes were compared between treatment groups also using a t-test with two different MMRM models as sensitivity models, one including baseline clinical outcome score. The pharmacodynamic effect of govorestat was assessed by correlating galactitol level at 3 months with change from baseline in clinical measures at 18 months using a Pearson correlation. Govorestat treatment resulted in a rapid and sustained reduction in plasma galactitol. Govorestat treatment stabilized or improved clinical measures of behavior, daily living skills, adaptive skills, cognition, tremor, and fine motor skills, which declined over time in the placebo group. Govorestat treatment did not demonstrate a benefit compared with placebo on speech outcomes or gross motor skills, which improved in both treatment groups over 18 months. Govorestat was safe and well tolerated, with adverse events well balanced between the active and placebo groups. Aldose reductase inhibition with govorestat represents a potential opportunity to lower galactitol and improve clinical outcomes in children with Classic Galactosemia.

Efficacy oF «Galavit®» in combination therapy of ari аnd influenza in adult patients: results of a multicenter randomized double-blind placebo-controlled study

Efficacy oF «Galavit®» in combination therapy of ari аnd influenza in adult patients: results of a multicenter randomized double-blind placebo-controlled study

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase2b Study.

In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs). This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI). A mixed model for repeated measures was used to estimate changes in PRO scores from baseline; scores were also compared with clinically meaningful change benchmarks. The analysis included 267 subjects, mean (SD) age 37.9 (14.7) years, 40.8% female; 55.1% grade3 and 44.9% grade4 Investigator Global Assessment for AD. Mean (SD) scores were: Worst Pruritus NRS 7.5 (1.9), Sleep Disturbance NRS 5.5 (2.9), DLQI total score 12.6 (7.1). Worst Pruritus and Sleep NRS scores had low positive correlations with SCORing AD (SCORAD) score (r = 0.44, r = 0.45 respectively) and negligible correlations with Eczema Area and Severity Index (EASI) score and area affected (r < 0.30). DLQI score varied by sex, study country, race, age, longer disease duration, disease severity (EASI and SCORAD), presence of asthma, and Worst Pruritus NRS, Sleep disturbance NRS, and DLQI scores. Rocatinlimab showed benefit on all three PROs, with significant improvements from baseline at the end of the double-blind period (week18) and active treatment extension (week36). Benefits were maintained over 20weeks' post-treatment follow-up. The benefit of rocatinlimab treatment on PROs is rapid and maintained for at least 20weeks following treatment completion. This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit. ClinicalTrials.gov identifier, NCT03703102.

Enhanced Bioavailability and Immune Benefits of Liposome-Encapsulated Vitamin C: A Combination of the Effects of Ascorbic Acid and Phospholipid Membranes

The bioavailability of vitamin C, or ascorbic acid, depends on limiting transport mechanisms that may be bypassed by liposome-encapsulation. The goal for this study was to evaluate the uptake, antioxidant, and immune-modulating effects of liposome-encapsulated vitamin C (LEC) using Lypo-Spheric® technology, compared to three controls: ascorbic acid (AA), the phospholipid fraction composing the liposome, and placebo. A double-blinded placebo-controlled cross-over study design involved twelve healthy participants attending four clinic visits. At each visit, a baseline blood draw was performed, followed by consumption of 1 g LEC, 1 g AA, the phospholipid component of LEC, or placebo. Additional blood draws were performed at 2, 4, and 6 h. Consuming LEC and AA increased blood levels of vitamin C; the levels were significantly higher after consuming LEC at all timepoints when compared to AA (p &lt; 0.01). LEC consumption increased serum antioxidant capacity (p &lt; 0.01 at 2 h) and protection. Consuming LEC increased IFN-γ levels at 6 h, while consuming the phospholipid fraction rapidly decreased inflammatory cytokines IL-6, MCP-1, and MIP-1α at 2 h. Consuming LEC provided enhanced vitamin C bioavailability and antioxidant protection compared to AA. Consuming the phospholipids had anti-inflammatory effects. The results suggest that LEC provides antioxidant and immune benefits above AA, useful in preventive medicine.

Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777

To investigate the safety and efficacy of ANG-3777, a hepatocyte growth factor mimetic, in mitigating the risk of acute kidney injury (AKI) in patients undergoing cardiac surgery with cardiopulmonary bypass. In this double-blind placebo-controlled study (GUARD), patients were randomized to receive intravenous ANG-3777 2 mg/kg or placebo once daily for 4 days. The primary endpoint was AKI severity, measured by mean area under the concentration-time curve on percent increase in serum creatinine from days 2 to 6. Secondary endpoints included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5. In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% CI, -6.2, 8.4; P = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; P = .60) or day 90 (14.7% vs 21.5%; P = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery following treatment with ANG-3777 than placebo. Overall, ANG-3777 was well tolerated, with similar incidences of treatment-emergent adverse events between treatment arms. Findings from this study do not support the efficacy of ANG-3777 in preventing the development of AKI following cardiopulmonary bypass.

Effect of supplementation with lutein, zeaxanthin, and omega-3 fatty acids on macular pigment and visual function in young adults with long-term use of digital devices: study protocol for a randomized double-blind placebo-controlled study.

Growing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices. The Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention. The trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health. www.clinicaltrials.in.th, Identifier, TCTR20220904002.

Evaluation of the effectiveness and safety of Korean red ginseng extract as immune-enhancer in Vietnamese adults: A randomized placebo-controlled trial

Purpose: To investigate the safety and immune-enhancing effect of Korean red ginseng (KRG) extract in Vietnamese adults. Methods: Participants in this randomized, placebo-controlled double-blinded study were administered either 960 mg of KRG extract (n = 51) or placebo capsules (n = 50) for 12 weeks at Hanoi Medical University, Vietnam. The KRG extract was standardized to contain 5.27 mg of 3 ginsenosides (Rg1, Rb1, and Rg3) per gram. Blood samples for assessment of treatment effectiveness were collected from the subjects on days 21 and 84. Immune cytokines were quantified using enzyme-linked immunosorbent assay (ELISA). Blood samples for safety assessment, hematological and biochemical variables, and urinalysis were performed at the beginning and end of the intervention (days 21 and 84, respectively). Results: The KRG group showed a significant increase in lymph T cell % at the end of the 12-week intervention (p &lt; 0.001). There were significant decreases in numbers of white blood cells (WBC) and natural killer (NK) cells in both groups. However, there were no significant differences in populations of WBC and NK cells between the 2 groups. Serum concentrations of cytokines, i.e., TNF-α, β, γ; IFN- α, γ; IL-1β and 4β were decreased in the KRG group when compared to baseline values. There were no probable or definite adverse events (AEs) related to KRG. A total of 9 participants (4 in KRG group and 5 in placebo group) tested positive for COVID-19 during the trial. Conclusion: The KRG extract-induced increase in population of T-cells and reductions in cytokine levels following a 12-week exposure may be beneficial for COVID-19 patients.

7038 Continuous Subcutaneous Hydrocortisone Infusion Is Practical And Effective In Select Patients With Adrenal Insufficiency

Abstract Disclosure: J.E. Lee: None. O. Hamidi: None. S. Mirfakhraee: None. Continuous subcutaneous hydrocortisone infusion (CSHI) via insulin pump is an alternative therapy for treating patients with adrenal insufficiency (AI) and allows for adjustable hydrocortisone delivery to provide more physiologic glucocorticoid replacement. Retrospective case series of 9 patients on CSHI showed a reduction in total daily dose of glucocorticoid by 34% and a decrease in hospitalization admissions due to adrenal crisis by 50%. In a double-blind placebo-controlled study, CSHI in patients with primary AI did not demonstrate benefit in subjective health status metrics compared to oral hydrocortisone; however, patients had good baseline subjective health scores. Due to a scarcity of data, CSHI is likely underutilized in patients who may benefit from this individualized therapy. Our research objectives were to analyze the change in total daily glucocorticoid dose, number of adrenal crises events and hospitalization days, glucocorticoid-related comorbidities, and quality of life of patients transitioned to CSHI. We performed a single-center, retrospective longitudinal follow-up study in 23 consecutive patients (87% women, median age 40 years at time of CSHI initiation) treated with CSHI between 2015 and 2023. Types of adrenal insufficiency were 48% secondary AI, 35% glucocorticoid induced AI, and 17% primary AI. CSHI delivery settings were generated by a formula that we derived using each patient’s daily oral glucocorticoid dose and preferred waking time. Median time from AI diagnosis to CSHI implementation was 41 months, and median duration of CSHI was 25 months. Total daily dose of glucocorticoid (in hydrocortisone equivalent) before CSHI vs during CSHI decreased from 30.0mg (15.0mg to 80.0mg) to 26.6mg (14.4mg to 200.5mg) (p= 0.45). Median number of adrenal crisis events decreased from 1 (0 to 13) to 0 (0 to 38) (p=0.25), and hospitalization days due to adrenal crisis decreased from 2 (0 to 46) to 0 (0 to 58) (p=0.53). No significant differences were noted for change in weight, blood pressure, diabetes, cardiovascular and cerebrovascular events, total cholesterol, LDL, and triglyceride levels. Median HDL decreased from 59 to 51 (p=0.01). In terms of subjective health status, 10 patients completed SF-36 survey while on CSHI. Significant impairments were noted in physical health, vitality, and general health with median score less than 40. At the conclusion of the study, 20 patients (87%) preferred CSHI therapy. Only 3 patients stopped CSHI for reasons of inconvenience, skin irritation at pump site, and better symptom control on oral therapy. No significant CSHI-related safety concerns were noted. In conclusion, CSHI is a safe and effective way to deliver individualized therapy to patients with difficult to control AI. CSHI led to reduction in glucocorticoid exposure and fewer adrenal crisis events and hospitalization days due to adrenal crisis. Presentation: 6/1/2024

Effect of Dalfamperidine on Cognitive Impairment, Gait Disorders and Fatigue in Multiple Sclerosis Patients

Abstract Background Multiple sclerosis (MS) is one of the most common disabling diseases of the Central Nervous System (CNS) especially during early adult life. Walking impairment is considered one of the most disabling symptoms to patient with MS. The only approved treatment for impaired ambulation in MS is Dalfampridine. Objective To investigate the effect of dalfampridine on gait, cognitive functions and fatigue in Egyptian patients with multiple sclerosis. Methods This randomized double blinded placebo-controlled study was conducted on 100 patients with multiple sclerosis undergoing assessment for cognition, gait and fatigue. Results Baseline characteristics of dalfampridine group significantly showed more infratentorial lesions in MRI and lesser use of symptomatic treatment compared to placebo group. Along with visuospatial functions that was better in placebo group and even though this current study showed significant improvement in dalfampridinegroup better than placebo as concluded by increased endpoint (mean difference) between two groups. Conclusions dalfampridine may has role in improvement of total EDSS.

Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects

Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lacking. Additionally, its mechanism of action has not been investigated in humans. We used a randomized, double-blind, placebo-controlled, crossover design in 16 healthy subjects (8 women) who received placebo, mescaline (100, 200, 400, and 800 mg), and 800 mg mescaline together with the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg) to assess subjective effects, autonomic effects, adverse effects, and pharmacokinetics up to 30 h after drug administration. Mescaline at doses >100 mg induced dose-dependent acute subjective effects. Mescaline increased systolic and diastolic blood pressure at doses >100 mg, with no difference between doses of 200-800 mg. Heart rate increased dose-dependently. Pharmacokinetics of mescaline were dose-proportional. Maximal concentrations were reached after approximately 2 h, and the plasma elimination half-life was approximately 3.5 h. The average duration of subjective effects increased from 6.4 to 14 h with increasing doses of 100-800 mg mescaline. Nausea and emesis were frequent adverse effects at the 800 mg dose. Co-administration of ketanserin attenuated and shortened acute effects of 800 mg mescaline to become comparable to the 100 and 200 mg doses. There were no ceiling effects of the subjective response within the investigated dose range, but tolerability was lower at the highest doses. These results may assist with dose finding for future research and suggest that acute effects of mescaline are primarily mediated by 5-HT2A receptors.

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial

Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30mL/min/1.73m2) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19). Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n=45) and 39.8% (n=35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p=0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3mL/min/1.73m2, 90% CI 0.51-8.12, p=0.06; and MAKE 6.7% (n=6) vs 15.9% (n=14); RR: 0.41, 90% CI: 0.19, 0.88, p=0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group). In this proof-of-concept study, RMC-035 did not reduce AKI 72h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes. Guard Therapeutics.

Effects of fructan and gluten on gut microbiota in individuals with self-reported non-celiac gluten/wheat sensitivity—a randomised controlled crossover trial

BackgroundIndividuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved.MethodsOur main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences).ResultsThe relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (β-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline.ConclusionsIn conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms.Trial registrationClinicaltrials.gov as NCT02464150.

Intermittent theta burst stimulation of the left dorsolateral prefrontal cortex has no additional effect on the efficacy of virtual reality exposure therapy for acrophobia. A randomized double-blind placebo-controlled study

Anxiety disorders are among the most common mental disorders. Treatment guidelines recommend pharmacotherapy and cognitive behavioral therapy as standard treatment. Although cognitive behavioral therapy is an effective therapeutic approach, not all patients benefit sufficiently from it. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, have been investigated as promising adjuncts in the treatment of affective disorders. The aim of this study is to investigate whether a combination of intermittent theta burst stimulation (iTBS) and virtual reality exposure therapy leads to a significantly greater reduction in acrophobia than virtual reality exposure with sham stimulation. In this randomized double-blind placebo-controlled study, 43 participants with acrophobia received verum or sham iTBS over the left dorsolateral prefrontal cortex prior to two sessions of virtual reality exposure therapy. Stimulation of the left dorsolateral prefrontal cortex with iTBS was motivated by an experimental study showing a positive effect on extinction memory retention. Acrophobic symptoms were assessed using questionnaires and two behavioral approach tasks one week before, after treatment and six months after the second diagnostic session. The results showed that two sessions of virtual reality exposure therapy led to a significant reduction in acrophobic symptoms, with an overall remission rate of 79 %. However, there was no additional effect of iTBS of the left dorsolateral prefrontal cortex on the therapeutic effects. Further research is needed to determine how exactly a combination of transcranial magnetic stimulation and exposure therapy should be designed to enhance efficacy.

50233 Rocatinlimab Significantly Improves Clinical Responses in Patients with Moderate-To-Severe Atopic Dermatitis by Week 2 in a Randomized Double-Blind Placebo-Controlled Phase 2b Study

50233 Rocatinlimab Significantly Improves Clinical Responses in Patients with Moderate-To-Severe Atopic Dermatitis by Week 2 in a Randomized Double-Blind Placebo-Controlled Phase 2b Study

PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial

IntroductionTuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for...

Gaba-producing lactobacilli boost cognitive reactivity to negative mood without improving cognitive performance: A human Double-Blind Placebo-Controlled Cross-Over study

BackgroundPsychobiotic bacteria are probiotics able to influence stress-related behavior, sleep, and cognitive outcomes. Several in vitro and human studies were performed to assess their physiological potential, to find strains having psychotropic activity in humans, and to elucidate the metabolic pathways involved. In our previous in vitro study, we identified two strains Levilactobacillus brevis P30021 and Lactiplantibacillus plantarum P30025, able to produce GABA and acetylcholine, being promising candidates to provide an effect on mood and cognitive performance. AimTo investigate the effects of probiotics in the alleviation on the cognitive performance of moderately stressed healthy adults. Secondary outcomes were related to mood improvement, production of GABA, glutamate, acetylcholine, and choline and modification of the microbiota composition. MethodsA 12-week randomized, double-blind, placebo-controlled, cross-over study investigated the effects of a probiotic formulation (Levilactobacillus brevis P30021 and Lactiplantibacillus plantarum P30025) on psychological, memory, and cognition parameters in 44 (Probiotic = 44, Placebo = 43) adults with a mean age of 29 ± 5.7 years old by CogState Battery test. Subjects-inclusion criteria was a mild-moderate (18.7 ± 4.06) stress upon diagnosis using the DASS-42 questionnaire. ResultsProbiotic treatment had no effect on subjective stress measures. The probiotic formulation showed a significant beneficial effect on depressive symptoms by reducing cognitive reactivity to sad mood (p = 0.034). Rumination significantly improved after intake of the probiotic (p = 0.006), suggesting a potential benefit in reducing the negative cognitive effects associated with depression and improving overall mental health. When stratifying the treated subjects according to the response, we found an increase in the abundance of the probiotic genera in the gut microbiota of positive responders (p = 0.009 for Lactiplantibacillus and p = 0.004 for L.brevis). No relevant correlations were observed between the neurotransmitter concentration in the faecal sample, scores of LEIDS, DASS-42, and cognitive tests. ConclusionWe highlight the potential of this probiotic preparation to act as psycobiotics for the relief of negative mood feelings. The assessment of the psychotropic effects of dietary interventions in human participants has many challenges. Further interventional studies investigating the effect of these psychobiotic bacteria in populations with stressed-related disorders are required including longer period of intervention and larger sample size in order to verify the effects of the treatment on further stress-related indicators.

Skin and Scalp Health Benefits of a Specific Botanical Extract Blend: Results from a Double-Blind Placebo-Controlled Study in Urban Outdoor Workers

Environmental pollution is increasingly recognized as a significant contributor to skin and scalp damage. Oral supplementation with a specific blend of four standardized botanical extracts (Rosmarinus officinalis, Lippia citriodora, Olea europaea leaf, and Sophora japonica) has been previously demonstrated to enhance skin health in individuals exposed to high environmental stress. Thus, it might represent a convenient strategy to also improve their scalp health aspect, particularly in subjects with sensitive scalps. To support these effects, a 12-week double-blind, randomized, placebo-controlled trial was performed in 66 women working outdoors in urban areas with high particulate matter (PM) levels and taking 250 mg of the botanical blend daily. Product efficacy was measured as follows: skin antioxidant status (FRAP); skin and scalp moisturization (corneometer), transepidermal water loss (tewameter), and oiliness (sebumeter); skin radiance and colour (spectrophotometer), elasticity and firmness (cutometer) and wrinkle depth (image analysis); and scalp clinical evaluation. Despite constant exposure to increased levels of PM, the tested product positively influenced all monitored parameters compared to both baseline and the placebo-treated group, in as early as 4 weeks. At the end of the study, key improvements included increased skin FRAP (21.9%), moisturization (9.5%), radiance (24.9%) and reduced wrinkle depth (−16.5%), dark spot pigmentation (−26.2%), and skin oiliness (−19.3%). For the scalp, moisturization increased (14.1%), TEWL decreased (−13.8%), and sebum content reduced by 16.2%. Additionally, 71% of subjects with sensitive scalps experienced reduced redness. These findings highlight the extensive benefits of the ingredient, expanding its application beyond conventional skin treatments to also alleviate scalp issues.

The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double-Blind Randomized Placebo-Controlled Cross-Over Study.

Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.