Parallel-group Trial Research Articles

The PATCH trial: 5% lidocaine-medicated plaster for trigeminal neuralgia-Results of a multicentric, enriched enrollment, randomized withdrawal, double-blind, vehicle-controlled, parallel-group study.

To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

Liraglutide enhances insulin secretion and prolongs the remission period in adults with newly diagnosed type 1 diabetes (the NewLira study): A randomized, double-blind, placebo-controlled trial.

To test the effect of the glucagon-like peptide-1 receptor agonist, liraglutide, on residual beta-cell function in adults with newly diagnosed type 1 diabetes. In a multicentre, double-blind, parallel-group trial, adults with newly diagnosed type 1 diabetes and stimulated C-peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8-mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow-up with only insulin treatment. The primary endpoint was the between-group difference in C-peptide area under the curve (AUC) following a liquid mixed-meal test after 52 weeks of treatment. Sixty-eight individuals were randomized. After 52 weeks, the 4-hour AUC C-peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end-of-treatment, C-peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo-treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. Treatment with liraglutide improves residual beta-cell function and reduces the dose of insulin during the first year after diagnosis. Beta-cell function was similar at 6 weeks postliraglutide treatment.

Mirabegron 50 mg once daily, long-term treatment maximizes benefit in middle-aged and older people with overactive bladder syndrome: a systematic review and meta-analysis of nine phase II/III, randomized, double-blind, parallel-design, placebo-controlled, multicenter, and multinational trials.

The prevalence and severity of overactive bladder increase with age, and mirabegron is an approved treatment for this condition. This meta-analysis systematically evaluated the efficacy and safety of mirabegron compared with placebo for overactive bladder treatment. We searched PubMed and the Cochrane Library (30 October 2023) for relevant articles (source: MEDLINE, EMBASE, ClinicalTrials.gov, ICTRP, CINAHL). We included randomized controlled trials involving adults with overactive bladder syndrome that compared mirabegron with placebo treatment. Data were analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions [Review Manager (computer program) Version 5.4]. Nine parallel-group trials (10 articles) were included. The evaluation included a total of 8,527 adults, including 6,445 women and 2,082 men, of whom 5,726 were White, 2,462 were Asian, and 161 were Black. The mean age of the participants ranged from 53.4 to 60.3 years. This evaluation involved three specifications of mirabegron: 25 mg, 50 mg, and 100 mg. In all trials, patients were enrolled in a 12-week double-blind treatment period, and the dose was once daily. The review of trials found that on average, people taking mirabegron had about 13 ml more volume voided per micturition, five fewer micturitions, and four fewer incontinence episodes every week, with moderate improvements in quality of life. About one in five people taking the drug reported TRAEs. Mirabegron treatment is well tolerated, with the risk of adverse events similar to that of a placebo. For best results, a dose of 50 mg once daily is recommended for long-term use. It is unclear whether any benefits are sustained after treatment discontinuation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023430737).

Effects of Pilates Training on Physical, Physiological and Psychological Performance in Young/Adolescent Volleyball Players: A Randomized Controlled Trial

Young athletes are constantly developing, and their performance reflects this ongoing process. By understanding performance variations and implementing appropriate training strategies, coaches and stakeholders can help young athletes develop their skills and athletic potential, as well as psychological well-being. Volleyball skills, such as explosive strength and serving precision, play a crucial role in determining the outcomes of volleyball matches. In contrast, mental well-being contributes to enhancing psychological performance. This prospective, randomized, parallel-group trial investigates the effectiveness of Pilates for young volleyball players. We investigated whether Pilates improves certain individual volleyball skills (explosive strength and serving precision) and certain psychological aspects (state of mindfulness) in young, male, 12–14-year-old athletes. Participation in this 12-week study involved 40 athletes (PG = 20; CG = 20). The Control Group had regular training and the Pilates Group had regular training plus twenty-four additional Pilates sessions. The Pilates Group showed a significant improvement in the variables under investigation by 4–7% (p &lt; 0.001). Pilates training can improve individual volleyball skills in young male athletes and may also benefit overall psychophysical development. This study suggests that incorporating Pilates into training programs for young volleyball players can be beneficial for individual skill development and potentially overall psychophysical well-being, assuming an important role in the educational development of the young.

LSDDEP2: study protocol for a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients with major depressive disorder

BackgroundMajor depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo.MethodsThis is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 μg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures.DiscussionThis study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants’ naturalistic environment. The measures included are designed to assess the drug’s safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials.Trial registrationANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024.

The impact of probiotics on core autism symptoms - A systematic review and meta-analysis of randomized clinical trials

Background & AimsStudies have shown evidence of gut dysbiosis in individuals with autism spectrum disorder (ASD). Various microbiome-modifying treatments, including probiotics, have been proposed. This review systematically assessed the evidence on the effects of probiotics on core autism symptoms in children with ASD. MethodsWe performed a comprehensive literature search in Medline, Embase, CENTRAL, PsycInfo, and clinical trial registries, up to March 2023, and updated on January 10, 2024. Randomized controlled trials (RCTs) of parallel-group and cross-over designs were eligible. The population included individuals below 20 years of age diagnosed with ASD. Trials evaluating the effects of probiotics (any strain or dose) compared to placebo, no treatment, or another intervention were included. The outcomes of interest included the core autism symptoms: deficits in social skills, communication skills, and restricted, repetitive behaviors. No language restrictions were applied. Studies were excluded if an additional active compound was administered. The risk of bias was assessed using the Revised Cochrane Risk of Bias tool (RoB 2). This review was registered in PROSPERO (CRD42023393000). ResultsIn total, 12 RCTs assessing 630 participants were included. A borderline significant beneficial effect of probiotics on core ASD symptoms was found (8 RCTs, mean difference -0.21; 95% CI –0.39 to -0.03). Subgroup analysis according to study type showed a significant positive effect in parallel group trials (6 RCTs, mean difference -0.26; 95% CI –0.48 to -0.05). The pooled effect estimates for the other outcomes didn’t reveal significant differences between the groups. Importantly, the risk of bias was high in nine studies. ConclusionsAvailable data do not provide high-quality evidence supporting the use of probiotics for ASD symptoms in children.

Comapring a lower dose of carbetocin to the standard dose of carbetocin in the prevention of postpartum hemorrhage during elective cesarean delivery: A randomised parallel group trial

Prophylactic use of uterotonic is a universal practice in vaginal and cesarean delivery. Heat stable carbetocin is a relatively new uterotonic. Lower doses of uterotonics are as effective as standard doses in elective cesarean deliveries. This study aimed to compare the effectiveness and safety of 50 mcg carbetocin (lower dose) to 100mcg carbetocin (standard dose) for the prevention of postpartum hemorrhage during elective cesarean delivery. A total of 212 term pregnant women were randomized to two group. Group I received 50 mcg of carbetocin and Group II received 100 mcg of carbetocin. The blood loss, tone of the uterus, use of additional uterotonics or styptics, requirement of blood transfusions and adverse effects of the drug in both the groups were compared. There were no statistically significant differences in both the groups with respect to blood loss, uterine tone, blood transfusions or additional use of uterotonics or styptics.(p&amp;#62;0.05).: A lower dose of 50 mcg is as effective as the standard dose of 100 mcg of carbetocin in elective caesarean delivery in preventing post-partum hemorrhage.

Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial

BackgroundImmune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies. ObjectiveTo evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects. MethodsThis 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis. ResultsThere were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ2=1.9, P =.48) or a significant time × treatment interaction (χ2=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups’ reduction in HAM-D-17 scores from the start to the endpoint (χ2= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ2=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ2=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively). ConclusionThe current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.

Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference -1.7%; 95% confidence interval -7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 .

Anti-hyperlipidemic effects of 500 mg spilanthol (SA3X) supplementation in people with dyslipidemia- a randomized, parallel-group placebo-controlled trial.

Dyslipidemia is a critical risk factor for cardiovascular disease. This study investigated the impact of 500 mg of spilanthol (SA3X) supplementation on lipid profiles in men with dyslipidemia using a randomized, parallel-group, placebo-controlled design. A total of 279 male participants were randomly allocated to one of four groups: SA3X without exercise, placebo without exercise, SA3X with exercise, and placebo with exercise. After a one-month control period, participants received SA3X capsules or placebo for three months. The exercise groups undertook standardized weight-lifting exercises four times weekly. Lipid profiles, biochemical parameters, and anthropometric measurements were monitored throughout and after the intervention. Both SA3X groups exhibited significant reductions in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared to the placebo groups. By day 90, the SA3X-no-exercise group showed a 16.78 % decrease in TC, while the SA3X-plus-exercise group demonstrated a 52.87 % decrease compared to placebo. Significant reductions in TG and LDL-C were noted at days 60 and 90 (p=0.01 and p=0.03, respectively). The SA3X-plus-exercise group also exhibited decreased random blood sugar levels at days 60 and 90 compared to placebo-plus-exercise. Moreover, decreases in C-reactive protein, creatine kinase, and serum creatinine levels were observed. SA3X supplementation, particularly when combined with exercise, effectively improved lipid profiles and various health markers in men with dyslipidemia. Adverse events, primarily taste disturbance, were mild. These findings suggest SA3X may be a promising adjunctive therapy for managing dyslipidemia, emphasizing its potential cardiovascular health benefits and supporting further investigation. CTRI/2021/05/033694; May 2021.

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Combination of a monofocal and one type of extended depth-of-focus (zonal refractive) intraocular lens (COMEDI) in bilateral cataract surgery protocol: a monocentric, randomised, parallel group trial in cataract surgery

IntroductionModern intraocular lens (IOL) designs for cataract treatment can be broadly classified into three focal range categories; monofocal, extended depth-of-focus (EDOF) and multifocal IOLs.Monofocal IOLs allow spectacle independence for one...

Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial

A small amount of evidence suggests that nasal sprays, or physical activity and stress management, could shorten the duration of respiratory infections. This study aimed to assess the effect of nasal sprays or a behavioural intervention promoting physical activity and stress management on respiratory illnesses, compared with usual care. This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment. Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76-0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74-0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89-1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30-1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63-1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74-1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50-0·84; p=0·001) for the gel-based spray group; 0·69 (0·45-0·88; p=0·003) for the saline spray group; and 0·74 (0·57-0·94; p=0·02) for the behavioural website group. Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions. National Institute for Health and Care Research.

Daily Self-Monitoring and Feedback of Circadian Rhythm Measures in Major Depression and Bipolar Disorder Using Wearable Devices and Smartphones-The Circadian Rhythm for Mood (CRM®) Trial Protocol: A Randomized Sham Controlled Double-Blind Trial.

The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Can a 6-Month Exercise Training Program Improve Musculoskeletal Health in Individuals with Systemic Lupus Erythematosus post Glucocorticoid Pulsetherapy? Protocol for a Randomized Controlled Trial

ABSTRACT Background Systemic lupus erythematosus is an autoimmune condition characterized by immune dysregulation, exacerbated systemic inflammation, and tissue damage. Glucocorticoid (GC) pulse therapy is a pharmacological strategy used to manage high activity phases. Although clinically effective, it can lead to adverse effects, including compromised musculoskeletal health. Adjuvant therapies that allow maintenance of the clinical benefits of pulse therapy, while preventing or attenuating these adverse effects, are warranted. Exercise training has the potential to counteract these adverse effects, but the efficacy and viability of this approach has yet to be explored. Hence, this randomized, controlled, parallel-group trial aims to investigate the effects of a home-based, supervised, 6-month exercise training program on a battery of musculoskeletal health parameters in women with systemic lupus erythematosus who recently underwent GC pulse therapy. Methods After baseline assessments, participants will be randomized to either the control or exercise group. Participants in both groups will receive usual care, while those randomized to the exercise group will also undergo a multimodal training program. Outcomes will be examined at baseline and after 3 and 6 months. Primary outcomes include bone mineral density by dual-energy x-ray absorptiometry, bone microarchitecture by high-resolution peripheral quantitative computed tomography, and circulating levels of bone turnover markers (β-CTX and PINP). Secondary outcomes include body composition, muscle strength and function, and aerobic capacity as well as feasibility and acceptability metrics. Conclusion The information gained from this investigation has the potential to inform care and management strategies for this and similarly affected patient groups.

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination ComparedWith Placebo for Initial Treatment of Hypertension.

Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension. We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety. This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154mmHg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10mg/amlodipine 1.25mg/indapamide 0.625mg), GMRx2 ½ dose (telmisartan 20mg/amlodipine 2.5mg/indapamide 1.25mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event. From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86mmHg and clinic BP was 138/86mmHg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were-7.3mmHg (95% CI: -4.5 to-10.2) for GMRx2 ¼ dose and-8.2mmHg (95% CI: -5.2 to-11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9mmHg. At Week 4, clinic BP control (<140/90mmHg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P< 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium<130/>150mmol/L or potassium<3.0/>6.0mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group. In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).

Evaluation of Add-On Individualized Homeopathic Medicines Products in the Treatment of Symptomatic COVID-19 Managed at Home: A Double Blind, Placebo-Controlled, Randomized, Exploratory Clinical Trial

Homeopathy has shown promise in fighting epidemics, leading to potential applications in the COVID-19 clinical cases. To assess the impact of add-on individualized homeopathic medicinal products (IHMP) in improving clinical outcomes and time to medical discharge in COVID-19 patients. A prospective, double-blind, randomized, placebo-controlled, parallel-group exploratory clinical trial was conducted in a São Paulo state municipality, Brazil, between February and July 2021. 82 (unvaccinated) patients with confirmed SARS-CoV-2 infection and manageable mild to moderate COVID-19 symptoms were randomly assigned to placebo or IHMP groups. Utilizing unique global COVID-19 symptom scores, a symptom assessment was performed. Statistical analysis involved 68 patients (36 IHMP; 32 placebo). No significant initial disparity existed in total COVID-19 symptom scores between the groups. The IHMP group exhibited a significantly shorter mean time from initial appointment to medical discharge compared to placebo (p &lt; 0.05: IHMP 74.5 hours (+/- 57.47, 95% CI: 55.73-93.27); placebo 137.42 hours (+/- 87.85, 95% CI: 106.98-167.86)). Employing the chi-square trend test at selected time points (74.5 and 137.42 hours, corresponding to mean discharge times), COVID-19 scores demonstrated sustained IHMP-associated reductions (p &lt; 0.05). COVID-19 symptom scores and time to medical discharge were significantly reduced by treatment with IHMP compared to placebo, suggesting a potential role for IHMP in managing mild to moderate COVID-19 symptoms at home.

Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Postbiotics could exert different metabolic activities in animal models of non-alcoholic fatty liver disease (NAFLD) and in humans affected by metabolic syndrome. This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial that enrolled a sample of 50 Caucasian healthy individuals with NAFLD, defined as liver steatosis, and metabolic syndrome. After a 4-week run-in, the enrolled individuals were randomized to take a food for special medical purposes with functional release, one tablet a day, containing calcium butyrate (500 mg/tablet), zinc gluconate (zinc 5 mg/tablet), and vitamin D3 (500 IU/tablet), or an identical placebo for 3 months. Liver and metabolic parameters were measured at baseline and at the end of the study. No subject experienced any adverse events during the trial. In both groups, a significant decrease in total cholesterol (TC) and triglycerides (TG) plasma levels was observed at the randomization visit vs. pre-run-in visit (p < 0.05). Regarding liver parameters, after treatment, the fatty liver index (FLI) improved significantly vs. baseline values (p < 0.05) and vs. placebo group (p < 0.05) in the active treatment group, and the hepatic steatosis index (HSI) improved significantly vs. baseline values (p < 0.05). Moreover, after active treatment, TC, TG, and gamma-glutamyl transferase (gGT) improved significantly vs. baseline values (p < 0.05), and TC and TG improved vs. placebo group (p < 0.05), as well. In the placebo group, liver parameters remained unchanged after treatment; only TG improved significantly vs. baseline values (p < 0.05). In our study, we observed that the butyrate-based formula improved FLI and plasma lipid patterns in individuals affected by liver steatosis and metabolic syndrome.

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial.

There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment. This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC). Amino acid targets were 2.0g/kg per day in the AAS group and 1.2g/kg per day in the SC group. The AAS group received additional amino acids intravenously, while the SC group received an iso-energetic 5% glucose intravenously. Overall, 407 patients (AAS group, 204; SC group, 203) were included in this study. During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs. 25.16kcal/kg per day, P=0.493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than that in the SC group (1.81 vs. 0.94g/kg per day, P<0.001). The infection incidence during hospitalization and that within 30 days of surgery was significantly lower in the AAS group than that in the SC group (P=0.031 and P=0.024, respectively). The 30-day postoperative incidence of amino acid treatment-related adverse events and other complications did not significantly differ between the two groups. The postoperative hospital stay was significantly different between the two groups (P<0.001). AAS was associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy.

Effect of Mediterranean diet or mindfulness-based stress reduction during pregnancy on placental volume and perfusion: A subanalysis of the IMPACT BCN randomized clinical trial.

The IMPACT BCN trial-a parallel-group randomized clinical trial where 1221 pregnant women at high risk for small-for-gestational age (SGA) newborns were randomly allocated at 19- to 23-week gestation into three groups: Mediterranean diet, Mindfulness-based Stress reduction or non-intervention-has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion. Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8-week Stress reduction program adapted for pregnancy, consisting of weekly 2.5-h and one full-day sessions. Non-intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36-week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion. While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non-intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99-28.09] in Mediterranean diet and 20.44 [5.13-81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups. Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth.