Parallel-group Comparative Trial Research Articles

Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial.

Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

Lactobacillus paragasseri SBT2055 Activates Plasmacytoid Dendritic Cells and Improves Subjective Symptoms of Common Cold in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Comparative Trial.

This study investigated whether Lactobacillus paragasseri SBT2055 (LG2055) activates plasmacytoid dendritic cells (pDCs) and suppresses common cold symptoms in healthy adults. Cell-based experiments showed that a LG2055 treatment upregulated CD86 and HLA-DR expression in pDCs, indicating that LG2055 activates pDCs in vitro. In a subsequent randomized, double-blind, placebo-controlled, parallel-group comparative trial, 200 participants were randomly divided into two groups and consumed three capsules with or without LG2055 once daily for 12 weeks. The primary outcome was the score on a daily physical health questionnaire survey of common cold symptoms. Three participants discontinued the trial and six participants were excluded from the analysis, thus 191 participants (95 in the LG2055 group and 96 in the placebo group) were analyzed. The LG2055 group showed a significantly higher ratio of "without symptoms" responses for runny nose, plugged nose, sneezing, sore throat, hoarseness, and chill than the placebo group. Furthermore, a stratified analysis revealed that LG2055 intake enhanced CD86 and HLA-DR expression in the pDCs of the participants with low secretion rates of salivary secretory immunoglobulin A. These data suggest that LG2055 suppresses the subjective symptoms of the common cold by activating pDCs and improving the host's immune system in healthy adults, especially in immune-weakened individuals (UMIN000049183).

In children with cow's milk allergy, 1-kestose affects the gut microbiota and reaction threshold.

Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans. We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow's milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition. Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels. Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA. A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow's milk allergy. The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels. This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.

Effectiveness of an oral health curriculum in reducing dental caries increment and improving oral hygiene behaviour among schoolchildren of Ernakulam district in Kerala, India: study protocol for a cluster randomised trial

IntroductionChildren’s learning abilities suffer when their oral health is compromised. Inadequate oral health can harm children’s quality of life, academic performance, and future success and achievements. Oral health problems may...

Combination of poly-γ-glutamic acid and galactooligosaccharide improves intestinal microbiota, defecation status, and relaxed mood in humans: a randomized, double-blind, parallel-group comparison trial.

The genus Bifidobacterium comprises beneficial intestinal bacteria that play a crucial role in the regulation of human health. Traditional prebiotics are known to increase intestinal bifidobacteria by supplying a carbon source necessary for their growth. However, intestinal bifidobacteria need not only a carbon source but also a nitrogen source for growth. Moreover, the growth of bifidobacteria is known to be inhibited in a culture medium that does not contain glutamic acid. Based on these reports, we hypothesized that the combined intake of traditional prebiotics and glutamic acid would be beneficial for growth of bifidobacteria in the gut. In this study, we investigated the effects of the combination of galactooligosaccharide (GOS; traditional prebiotic material) and poly-γ-glutamic acid (γ-PGA; source of glutamic acid) and only GOS on the intestinal microbiota and health conditions (including intestinal regulation, mood status, gastrointestinal condition, skin condition, and sleep quality) in a randomized, double-blind, parallel-group comparison trial in healthy subjects. The combined intake of GOS and γ-PGA significantly increased the prevalence of B. longum compared to the intake of GOS alone. A minimum effective dose of 2.0 g GOS and 0.3 g γ-PGA improved defecation and mood status. We revealed the combined effects of GOS and γ-PGA on intestinal microbiota as well as physical condition and concluded that the delivery of glutamic acid to the large intestine with traditional prebiotics is useful as an advanced prebiotic.

Efficacy of periodontal soft tissue augmentation prior to orthodontic treatment on preventing gingival recession: study protocol for a randomised controlled trial

IntroductionIn adult patients with thin phenotype, gingival recession is obvious in the mandibular incisors after a large amount of lingual tooth movement. A systematic review indicated that soft tissue augmentation...

Randomized double-blind placebo-controlled multicenter trial for the effects of a polyherbal remedy, Yokukansan (YiganSan), in smokers with depressive tendencies

BackgroundSmoking and depression are closely related and form a vicious cycle. Yokukansan (YiganSan) is a polyherbal remedy that has the effect of calming neuropsychiatric symptoms such as anger and irritation. To examine the efficacy of Yokukansan during smoking cessation (SC) therapy in smokers with depressive tendencies but without major depressive disorders requiring pharmacotherapy.MethodsA multicenter, double-blind, randomized, placebo-controlled, parallel-group comparison trial was conducted between June 2016 and May 2020 at 12 centers of the National Hospital Organization, Japan. This trial targeted smokers who first visited the SC outpatient clinics, did not receive any pharmacological treatment at the psychiatric or psychosomatic department, and scored 39 or more on the self-rating depression scale (SDS). Participants (n = 198) were randomly assigned to either the Yokukansan or placebo groups. The trial drug was initiated with the start of the SC treatment and continued for 12 weeks. The primary outcome was the high success rate of the SC treatment, and the secondary outcomes included changes in scores of the SDS and the Profile of Mood States (POMS) instrument.ResultsThe success rate of the SC treatment was similar between the placebo (63%) and Yokukansan (67%) groups (P = .649). The SDS scores (placebo: mean difference [MD] = -3.5, 95% confidence interval [CI][-5.8, -1.2], d = 0.42; Yokukansan: MD = -4.6, 95%CI[-6.8, -2.3], d = 0.55), and the “tension-anxiety” POMS-subscale scores (placebo: MD = -1.6, 95%CI[-2.5, -0.7], d = 0.52; Yokukansan: MD = -1.6, 95%CI[-2.9, -0.3], d = 0.36) showed significant improvement in both groups after the SC treatment. However, “depression-dejection” improved in the Yokukansan group (MD = -1.9, 95%CI[-3.1, -0.7], d = 0.44) but not in the placebo group (MD = -0.1, 95%CI[-1.0, 0.7], d = 0.04). Significant improvement in “fatigue” was noted in the Yokukansan group (MD = -2.1, 95%CI[-3.4, -0.9], d = 0.47) but not in the placebo group (MD = -0.5, 95%CI[-1.8, 0.8], d = 0.11). The time × group interaction on the improvement in “depression-dejection” was significant (P = .019).ConclusionsYokukansan does not increase the SC treatment’s success rate but has additional positive effects on the psychological states due to the SC treatment in smokers with depressive tendencies but without apparent mental disorders.Trial registrationID: UMIN000027036. Retrospectively registered at UMIN on April 18, 2017.

Koji amazake Maintains Water Content in the Left Cheek Skin of Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Comparative Trial.

PurposeImprovement in water content and skin barrier function on human skin is believed to be induced by koji amazake, a non-alcoholic beverage derived from rice fermented by Aspergillus oryzae (A. oryzae). In order to scientifically identify the effects of koji amazake on human skin, we performed a randomized, double-blind, placebo-controlled, parallel-group comparative trial and quantified the content of glucosylceramide (GlcCer) which would be responsible for the effects.Participants and MethodsHealthy adults concerned with their skin dryness were divided into koji amazake (N = 30) or placebo group (N = 30). During this test, the test beverages were ingested at 118 g/day. Their water content and trans-epidermal water loss (TEWL) were measured at 0 week (baseline) and 8 weeks. The content of GlcCer in test beverages was quantified by HPLC-ELSD.ResultsIn comparison with the placebo group, the water content in the left cheek of individuals in the koji amazake group was maintained for 8 weeks. In addition, changes in water content from the baseline to 8 weeks differed significantly between the koji amazake (0.19) and placebo groups (−3.98). Unexpectedly, there was no significant difference in the TEWL between koji amazake and placebo group. We analyzed GlcCer in both koji amazake and placebo beverages, which were found to contain 1.35 ± 0.11 and 0.30 ± 0.07 mg/118 g, respectively. The amount of GlcCer in koji amazake was approximately equal to the dosage of plant-derived GlcCer which has the ability to improve water content and TEWL in humans.ConclusionPresent study has shown that intake of koji amazake contributes to maintain the water content only on the left cheek. The content of GlcCer derived from koji amazake was adequate for maintenance of the water content compared to previous reports. Therefore, it was concluded that GlcCer in koji amazake acts as a functional ingredient.

Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study

BackgroundDue to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). Methods and resultsThe Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. ConclusionsRegardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.

Immediate mobilization of distal radius fractures stabilized by volar locking plate results in a better short-term outcome than a five week immobilization: A prospective randomized trial

Objective: To evaluate the impact of immediate (first day after surgery) mobilization compared to standard five weeks cast immobilization on the functional outcome after volar locking plate fixation of distal radius fractures. Design: Prospective randomized parallel group comparative trial. Setting: Trauma Hospital, Austria. Participants: Patients with isolated unstable distal radius fractures, stabilized with volar angular stable locking plate. Interventions: The immediate mobilization group received a removable forearm splint for one week and active supervised group physiotherapy and home exercises for the shoulder, elbow, wrist, and fingers from the first postoperative day. The cast immobilization group received a non-removable cast for five weeks. In the first five weeks supervised group physiotherapy and home exercises were performed for shoulder, elbow, and fingers. Thereafter additional supervised and home exercises for the wrist were started. Main measures: At regular intervals of six and nine weeks, three and six months, and one year post surgery range of motion, grip strength, and x-rays were evaluated. Additionally, the shortened disabilities of the arm, shoulder and hand (QuickDASH) score, Patient-rated Wrist Evaluation, Mayo Wrist score, and pain according to the Visual Analog Scale score were analyzed. Results: One hundred and sixteen patients were prospectively randomized into two study groups. At the one-year follow-up, patients in the immediate mobilization group showed a significantly higher range of motion in extension/flexion (mean difference 10.2°, 99% confidence interval 0.6–19.8), grip strength (mean difference 5.1 kg, 99% confidence interval −0.5 to 10.7), and Mayo Wrist score (mean difference 7.9 points, 99% confidence interval 2.3–13.5) than the cast immobilization group. Range of motion in supination/pronation (mean difference 13.4°, 99% confidence interval 1.5–25.3) and in radial/ulnar deviation (mean difference 6.3°, 99% confidence interval 0.9–11.7) differed significantly up to nine weeks favoring the immediate mobilization group. The Patient-rated Wrist Evaluation revealed significantly better scores after three months (mean difference 9.3 points, 99% confidence interval 0.5–18.1) and QuickDASH after six months (mean difference 7.3 points, 99% confidence interval 0.3–14.3) in the immediate mobilization group. All other subsequent follow-up examinations indicated no significant differences in respect of pain, range of motion, and patient-reported outcome measurements between the study groups. There were no significant differences in respect of radiological loss of reduction and complications between the groups. Conclusions: Immediate mobilization in combination with supervised physiotherapy of the wrist after volar locking plate fixation of unstable distal radius fractures results in a significantly improved range of motion and grip strength after one year compared to cast immobilization. No increased risk for loss of reduction and other complications was observed.

Lowering of blood pressure and pulse rate by switching from DPP-4 inhibitor to luseogliflozin in patients with type 2 diabetes complicated with hypertension: A multicenter, prospective, randomized, open-label, parallel-group comparison trial (LUNA study)

AimsSodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces clinic blood pressure (BP), but the effects on BP circadian rhythm remain unclear. The present study aimed to determine the nighttime antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. Materials and MethodsIn this randomized, open-label, parallel-group trial, patients treated with DPP-4i were either switched to luseogliflozin 2.5 mg/day (Luseo group;n = 30) or continued DPP-4i (DPP-4i group;n = 26). The patients undertook 24-h ambulatory BP monitoring before and 8 weeks after the group allocation. The primary endpoint was mean change in nighttime systolic BP (SBP). ResultsNighttime SBP, as well as daytime SBP, was significantly reduced in the Luseo group compared with the DPP-4i group (nighttime, −4.0 ± 11.4 vs. 3.6 ± 10.7 mmHg,P = 0.01; daytime, −4.4 ± 10.9 vs. 3.7 ± 11.9 mmHg,P = 0.01). Similarly, nighttimepulse rate(PR) was significantly reduced in the Luseo group (−2.0 ± 4.8 vs. 0.9 ± 4.8 bpm,P = 0.03). The proportion of patients with abnormal BP circadian rhythms (non-dipper pattern plus riser pattern) was significantly lower in the Luseo group (36.6% vs. 56.7%,P < 0.05). ConclusionsSwitching from DPP-4i to luseogliflozin decreased nighttime SBP and PR; moreover, BP circadian rhythm was improved.

Intake of Koji Amazake Improves Defecation Frequency in Healthy Adults.

Reportedly, the intake of koji amazake, a beverage made from steamed rice fermented by Aspergillus oryzae, improves defecation frequency. However, its functional ingredients and mechanism of action remain unclear. To compare the effects of koji amazake and a placebo beverage on defecation frequency and to identify the functional ingredients and mechanism of action, a randomized, placebo-controlled, double-blind parallel-group comparative trial was performed on two groups. The koji amazake had 302 ± 15.5 mg/118 g of A. oryzae cells, which was not in the placebo. Compared with the placebo group, the koji amazake group showed a significant increase in weekly defecation frequency at 2 weeks (5.09 days vs. 4.14 days), 3 weeks (5.41 days vs. 4.18 days), and 4 weeks (5.09 days vs. 3.95 days), along with an increase in the weekly fecal weight at 4 weeks (724 g vs. 501 g). The intake of koji amazake did not induce significant intergroup differences in the fecal SCFA concentration, whereas it significantly decreased the relative abundance of Blautia and significantly increased that of Bacteroides at 3 weeks. Therefore, koji amazake intake improved defecation frequency, and A. oryzae cells played potentially important roles as functional ingredients.

7-LB: Lowering of Blood Pressure and Pulse Rate by Switching from DPP-4 Inhibitor to Luseogliflozin in Patients with Type 2 Diabetes and Hypertension: A Multicenter, Prospective, Randomized, Open-Label, Parallel-Group Comparison Trial

Objective: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment had the effect of reducing blood pressure (BP) and cardiovascular events in recent mega-scale trials, but the effects on BP circadian rhythm remained unclear. The present study aimed to determine the nocturnal antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. Research Design and Methods: In this randomized, open-label, parallel-group trial, patients treated with DPP-4i were either switched to luseogliflozin 2.5 mg/day (Luseo group; n=30) or continued DPP-4i (DPP-4i group; n=26). The patients undertook 24-h ambulatory BP monitoring before and 8 weeks after the group allocation. The primary endpoint was mean change in nighttime systolic BP (SBP). Results: Changes in both nighttime and daytime SBP were significantly reduced in the Luseo group compared with the DPP-4i group (nighttime, −4.0±11.4 vs. 3.6±10.7 mmHg, P=0.01; daytime, −4.4±10.9 vs. 3.7±11.9 mmHg, P=0.01). Similarly, nighttime pulse rate (PR) was significantly reduced in the Luseo group compared with the DPP-4i group (−2.0±4.8 vs. 0.9±4.8 bpm, P=0.03). Abnormal BP circadian rhythms (non-dipper and riser types) were significantly decreased in the Luseo group (56.7% to 36.6%, P&amp;lt;0.05). Conclusions: Switching from DPP-4i to luseogliflozin decreased not only daytime but also nighttime SBP and PR, and improved BP circadian rhythm. These improvements could be some of the factors involved in the cardiovascular event suppression observed with SGLT2i therapy. Disclosure R. Hashimoto-kameda: None. K. Cho: None. H. Nomoto: None. A. Nakamura: Research Support; Self; Boehringer Ingelheim International GmbH, Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Taisho Pharmaceutical Co., Ltd. K. Omori: None. S. Kawata: None. H. Kameda: None. T. Atsumi: Research Support; Self; Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K. K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., UCB Japan Co. Ltd., Speaker’s Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Co., UCB Japan Co. Ltd. H. Miyoshi: Research Support; Self; Abbott Japan Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd. Funding Taisho Pharmaceutical Co., Ltd.

COMPARATIVE EFFICACY OF INTRAVITREAL RANIBIZUMAB MONOTHERAPY WITH COMBINED INTRAVITREAL RANIBIZUMAB AND LASER PHOTOCOAGULATION THERAPY IN THE MANAGEMENT OF DIABETIC MACULAR EDEMA.

Background: In this study, best corrected visual acuity and macular thickness were compared before and after intravitreal injection Ranibizumab monotherapy and combined therapy of injection Ranibizumab and laser, in patients with macular oedema ≥350µm measured with spectral domain OCT. Objective:Our specific objective is to identify the best treatment option in NPDR with macular thickness ≥350µm in Type 2 diabetic retinopathy patients depending upon the anatomical and functional outcome in each group. Method: Sixty (60) newly diagnosed eyes of NPDR with macular oedema (30 patients in each group) attending retina research clinic of Regional Institute of Ophthalmology,Kolkata were included in this study. Result: This parallel group comparison trial has shown that a combination of 3 consecutive monthly doses of intravitreal ranibizumab followed by modified grid laser therapy 7-10 days latter is more effective in reducing central macular thickness in comparison to only multiple injections of ranibizumab,but there is no difference in the final best corrected visual acuity attained in between the two groups. Conclusion: Laser photocoagulation along withanti-vascularendothelialgrowthfactoragentisthestrongerweapontofightagainstblindnessindiabeticmacularedema

Improved time in range and postprandial hyperglycemia with canagliflozin in combination with teneligliptin: Secondary analyses of the CALMER study.

Aims/IntroductionWe recently reported the beneficial effect of the combination of sodium–glucose cotransporter 2 inhibitor and dipeptidyl peptidase‐4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis.Materials and MethodsThe CALMER study was a multicenter, open‐label, prospective, randomized, parallel‐group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated.ResultsAll 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2–82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (−14.8% vs −7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group (P < 0.05).ConclusionsSodium–glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase‐4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy.

Reproducibility of Office and Out-of-Office Blood Pressure Measurements in Children: Implications for Clinical Practice and Research.

This study aimed to evaluate the reproducibility of office (OBP), ambulatory (ABP), and home blood pressure (HBP) measurements in children and adolescents, and their implications in diagnosing hypertension in clinical practice and in pediatric hypertension research. Apparently healthy children and adolescents referred for suspected hypertension were included. Measurements of 2-visit OBP, 7-day HBP, and 24-hour ABP were performed twice, 1 to 6 months apart. Reproducibility was quantified using the SD of differences between repeated measurements. The sample size of clinical trials comparing the efficacy of antihypertensive drugs using each method was calculated. Fifty-eight individuals were analyzed (mean age, 13.0±2.9 years, 60.3% boys). The reproducibility of 24-hour ABP (SD of differences 5.7/4.5 systolic/diastolic) and HBP (5.9/5.0 mm Hg) were comparable and superior to that of visit-2 OBP (9.2/7.8) and awake (6.7/5.5) or asleep ABP (7.6/6.1). As a consequence, a parallel-group comparative trial aiming to detect a difference in the effect of 2 drugs of 10 mm Hg systolic BP, would require 36 participants when using OBP measurements, 14 using 24-hour ABP, and 15 using HBP (102/34/42 respectively for detecting a 5 mm Hg difference in diastolic BP). For a crossover design trial, the corresponding sample sizes are 9/3/4 for systolic BP and 26/9/11 for diastolic, respectively. These data suggest that in children and adolescents 24-hour ABP and 7-day HBP have similar reproducibility, superior to OBP and daytime or asleep ABP. These findings have major implications in diagnosing hypertension in children in clinical practice and in designing clinical research trials in pediatric hypertension.

Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial

BackgroundTofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease.MethodsThe using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline.ResultsIn a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (– 109.3 [– 184.3, – 34.3] (mean change [95% CI] cm/s, p = 0.005; – 98.3 [– 172.6, – 24.1] cm/s, p = 0.010; – 104.7 [– 177.0, – 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models.ConclusionsTofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness.Trial Registration UMIN000017607. Registered 18 May 2015. (https://www.umin.ac.jp/icdr/index.html)

The effect of 24-week continuous intake of quercetin-rich onion on age-related cognitive decline in healthy elderly people: a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial.

Quercetin, a type of flavonoid, is believed to reduce age-related cognitive decline. To elucidate its potential function, we carried out a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial involving 24-week continuous intake of quercetin-rich onion compared to quercetin-free onion as a placebo. Seventy healthy Japanese individuals (aged 60 to 79 years old) were enrolled in this study. We examined the effect of quercetin-rich onion (the active test food) on cognitive function using the Mini-Mental State Examination, Cognitive Assessment for Dementia iPad version, and Neuropsychiatric Inventory Nursing Home version. The Mini-Mental State Examination scores were significantly improved in the active test food group (daily quercetin intake, 50 mg as aglycone equivalent) compared to the placebo food group after 24 weeks. On the Cognitive Assessment for Dementia iPad version for emotional function evaluation, we found that the scores of the active test food group were significantly improved, suggesting that quercetin prevents cognitive decline by improving depressive symptoms and elevating motivation. On the Neuropsychiatric Inventory Nursing Home version, we found significant effects on reducing the burden on study partners. Taking all the data together, we concluded that 24-week continuous intake of quercetin-rich onion reduces age-related cognitive decline, possibly by improving emotional conditions. Clinical trial register and their clinical registration number: This study was registered with UMIN (approval number UMIN000036276, 5 April 2019).

Effects of Lactoferrin on Prevention of Acute Gastrointestinal Symptoms in Winter: A Randomized, Double-Blinded, Placebo-Controlled Trial for Staff of Kindergartens and Nursery Schools in Japan.

This study investigated the preventive effects of lactoferrin (LF) on subjective acute gastrointestinal symptoms during the winter in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The eligible subjects were healthy adults working at kindergartens and nursery schools. We randomized the subjects to the Placebo group (0 mg/day), the Low LF group (200 mg/day), and the High LF group (600 mg/day) for 12 weeks. The prevalence of acute gastrointestinal symptoms was significantly lower in the High LF (13/112 vs. 26/116; p = 0.030) and the Low LF (13/107 vs. 26/116; p = 0.040) groups than in the Placebo group. The adjusted odds ratio for the prevalence of acute gastrointestinal symptoms was 2.78 (95% CI: 1.19–6.47) in the Placebo group compared with the High LF group. LF is useful to prevent acute gastrointestinal symptoms among childcare workers, who mainly consist of women.

Clinical Effects of Dietary Supplementation of Lutein with High Bio-Accessibility on Macular Pigment Optical Density and Contrast Sensitivity: A Randomized Double-Blind Placebo-Controlled Parallel-Group Comparison Trial.

Improvements in macular pigment optical density (MPOD) and contrast sensitivity after administration of 12 mg lutein alone and the timing at which efficacy is observed remain unknown. Therefore, lutein (12 mg), a crystalline formulation, was used in this study, considering its bioaccessibility. This study aimed to determine the effects of lutein administration for 16 weeks on MPOD, contrast sensitivity, and glare sensitivity, and changes in serum lutein levels were determined. The study subjects comprised 59 healthy male and female adults aged 20–69 years. The study diet included a placebo (placebo group) or a diet supplemented with 12 mg of lutein (lutein group). Each study diet was continuously administered for 16 weeks. At weeks 8 and 16, MPOD, contrast sensitivity, glare sensitivity, and serum lutein levels were evaluated. Compared with the placebo group, the lutein group showed significantly improved MPOD, contrast sensitivity, and glare sensitivity at week 16 and significantly increased serum lutein levels at weeks 8 and 16. Continuous administration of lutein for 16 weeks, considering its bioaccessibility, increased MPOD; it made the outlines of visible objects clearer and was effective in inhibiting decreases in visual function caused by glare from light.