Concomitant oral intake of purified clinoptilolite tuff (G-PUR) reduces enteral lead uptake in healthy humans

AbstractLead exposure can cause substantial organ damage. Enteral lead absorption may be reduced by concomitant intake of clinoptilolite tuff, a zeolite from natural sources. This study aimed to assess the effect of purified clinoptilolite tuff (G-PUR) on enteral lead uptake in adults using stable lead isotope 204Pb as a tracer. In this randomized, placebo-controlled, double-blind, parallel-group study, 42 healthy participants were randomized to receive oral G-PUR 2.0 g, 2 * 2.0 g, or placebo, together with 2.5 µg of 204Pb in water. The enrichment of 204Pb caused by the tracer in blood and urine was measured by mass spectrometry. G-PUR was well tolerated. The mean maximum 204Pb enrichment of 0.505% of total blood lead was significantly higher (p < 0.0001) in the placebo group compared to G-PUR 2.0 g (0.073%) or G-PUR 2 * 2.0 g (0.057%) group. Normalized 204Pb AUC0-192 was 86.5, 11.9, and 8.5% * h without and with G-PUR 2.0 g, and G-PUR 2 * 2.0 g, respectively (p < 0.0001 vs. placebo). This smaller 204Pb exposure was paralleled by a reduced urinary excretion in subjects receiving G-PUR. Concomitant oral intake of purified clinoptilolite tuff reduced enteral uptake of 204Pb in healthy humans by approximately 90%. The reduced bioavailability is demonstrable by a decrease of 204Pb tracer enrichment in blood and urine.Trial registration: clinicaltrials.gov identifier: NCT04138693, registered 24/10/2019.

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Effect of the Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, on Nocturnal Hypertension: A Post Hoc Analysis of the ESAX-HTN Study

American Journal of Hypertension ◽

10.1093/ajh/hpaa155 ◽

2020 ◽

Author(s):

Kazuomi Kario ◽

Sadayoshi Ito ◽

Hiroshi Itoh ◽

Hiromi Rakugi ◽

Yasuyuki Okuda ◽

...

Keyword(s):

Older Patients ◽

Target Organ Damage ◽

Organ Damage ◽

Effective Treatment Option ◽

Double Blind ◽

Nocturnal Hypertension ◽

Post Hoc Analysis ◽

Nocturnal Dipping ◽

Parallel Group ◽

Post Hoc

Abstract BACKGROUND Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure (BP) variability and a known risk marker for target organ damage and cardiovascular events. This study aimed to assess the differential BP-lowering effects of esaxerenone vs. eplerenone on nocturnal BP in hypertensive patients with different nocturnal dipping patterns. METHODS This was a post hoc analysis of the “Esaxerenone (CS-3150) Compared to Eplerenone in Patients with Essential Hypertension” study (NCT02890173), which was a phase 3, multicenter, randomized, controlled, double-blind, parallel-group clinical study conducted in Japan. Ambulatory BP monitoring data were collected. RESULTS Patients (n = 1,001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Reductions in nighttime systolic BP (95% confidence interval) were significantly greater with 2.5 and 5 mg/day esaxerenone vs. eplerenone (−2.6 [−5.0, −0.2] and −6.4 mm Hg [−8.8, −4.0], respectively). Esaxerenone significantly reduced nighttime BP from baseline compared with eplerenone in non-dippers with previously uncontrolled BP. In addition, esaxerenone did not markedly alter nighttime BP in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime BP were greater than eplerenone-induced decreases in older patients. CONCLUSIONS Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP.

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506 Samelisant: Baseline Characteristics from a Phase 2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy

SLEEP ◽

10.1093/sleep/zsab072.505 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A199-A199

Author(s):

Ramakrishna Nirogi ◽

Jyothsna Ravula ◽

Pradeep Jayarajan ◽

Satish Jetta ◽

Gopinadh Bhyrapuneni ◽

...

Keyword(s):

Therapeutic Option ◽

Demographic Data ◽

Fixed Ratio ◽

Study Drug ◽

Eligibility Criteria ◽

Double Blind ◽

Healthy Humans ◽

Parallel Group ◽

Secondary Endpoints ◽

Baseline Characteristics

Abstract Introduction histamine H3 receptor (H3R) antagonists/ inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent and selective H3R inverse agonist exhibited selectivity over 70 other targets. Samelisant showed wake-promoting and anticataplectic effects in orexin knockout mice suggesting its potential therapeutic utility in the treatment of EDS and cataplexy associated with narcolepsy. Safety and tolerability studies in animals and healthy humans suggested a favorable risk/benefit profile. Methods The current study is a 2 week treatment, multicenter, double-blind, placebo controlled, parallel-group study in patients with Narcolepsy with or without Cataplexy. Eligibility criteria include age between 18 to 50 years old, an ESS score of ≥ 12; and mean MWT time of < 12 minutes and a confirm diagnosis of narcolepsy as per ICSD-3. Further, the randomization will be stratified according to type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks in a fixed ratio of 1:1:1. The primary efficacy endpoint is change in maintenance of wakefulness test (MWT) score from baseline to week 2. Key secondary endpoints include change from baseline to week 2 in ESS and an improvement in CGI-S scores. Safety will be monitored by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results As of data cutoff date of Dec 20, 2020, a total of 54 subjects were completed in the study. The median age of subjects was 30 years (range: 18 - 50 years) with mean BMI of 28.6 (range: 18.3 - 43.1 kg/m2). Overall, 74% of subjects were female and 83% were Caucasian. Mean (SD) baseline values of MWT and ESS are 5.65 (3.5) and 16.7 (2.5), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling the subjects with Narcolepsy with or without Cataplexy, and the Data readout is expected in the second half of 2021. Support (if any):

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A Parallel-Group Comparison of Astemizole and Loratadine for the Treatment of Perennial Allergic Rhinitis

Journal of International Medical Research ◽

10.1177/030006059702500401 ◽

1997 ◽

Vol 25 (4) ◽

pp. 175-181 ◽

Cited By ~ 66

Author(s):

H Al-Muhaimeed

Keyword(s):

Allergic Rhinitis ◽

Statistical Significance ◽

Double Blind Study ◽

Perennial Allergic Rhinitis ◽

Double Blind ◽

Once Daily ◽

Runny Nose ◽

Parallel Group ◽

The Mean ◽

To Receive

The efficacy and safety of the two antihistamines, astemizole and loratadine, were compared in a double-blind study of 84 patients with perennial allergic rhinitis. Patients were randomized to receive orally either astemizole 10 mg once daily ( n = 40) or loratadine 10 mg once daily ( n = 44) for 1 week. No other antirhinitis medication was allowed during the study. By day 7 the mean daily symptom scores, recorded on diary cards, were lower in patients receiving astemizole than in those receiving loratadine for runny nose, itchy nose and sneezing, although not for blocked nose, and treatment differences only reached statistical significance for runny nose. After 7 days, 53.75% of patients on astemizole and 38.6% on loratadine were free of symptoms, and 87% of patients on astemizole described the treatment as good or excellent compared with 62% on loratadine. The present results suggest that astemizole may be more effective than loratadine in controlling symptoms of perennial allergic rhinitis.

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A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.6.1063 ◽

1990 ◽

Vol 8 (6) ◽

pp. 1063-1069 ◽

Cited By ~ 81

Author(s):

J Bonneterre ◽

B Chevallier ◽

R Metz ◽

P Fargeot ◽

E Pujade-Lauraine ◽

...

Keyword(s):

Group Analysis ◽

Loading Dose ◽

Breast Cancer Patients ◽

Double Blind ◽

Parallel Group ◽

Blind Comparison ◽

Prophylaxis Of Emesis ◽

To Receive ◽

Blind Crossover Study ◽

Double Blind Crossover Study

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

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Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

International Journal of Hypertension ◽

10.1155/2015/139465 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Ettore Malacco ◽

Stefano Omboni ◽

Gianfranco Parati

Keyword(s):

Blood Pressure ◽

Renal Damage ◽

Blood Pressure Response ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

Double Blind ◽

Treatment Groups ◽

Parallel Group ◽

Plaque Regression

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%;p=0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%;p=0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression.

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The Efficacy of Continuous Versus Intermittent Celecoxib Treatment in Osteoarthritis Patients with Body Mass Index ≥30 and <30 kg/m2

The Open Rheumatology Journal ◽

10.2174/1874312901307010032 ◽

2013 ◽

Vol 7 (1) ◽

pp. 32-37 ◽

Cited By ~ 5

Author(s):

George H Sands ◽

Pritha Bhadra Brown ◽

Margaret Noyes Essex

Keyword(s):

Body Mass Index ◽

Treatment Group ◽

Body Mass ◽

Hip Osteoarthritis ◽

International Study ◽

Continuous Treatment ◽

Intermittent Treatment ◽

Double Blind ◽

Parallel Group ◽

To Receive

Objective: Characterize the effect of body mass index (BMI) on the efficacy of continuous daily celecoxib treatment compared with intermittent celecoxib treatment. Methods: Prespecified exploratory analysis of a 24-week, double-blind, parallel-group, randomized, multicenter international study. 858 patients with knee or hip osteoarthritis (OA) were randomized to receive celecoxib 200 mg daily either as continuous or intermittent treatment. Efficacy was measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) total and subscale scores and the number of flare events. Results: Least squares mean increases (worsening) in WOMAC total scores were significantly less in the continuous treatment group than in the intermittent treatment group in patients with a BMI <30 kg/m2 (1.33 vs 4.85; p=0.016) and in patients with a BMI ≥30 kg/m2 (1.84 vs 5.12; p=0.019). There was a greater worsening in patients with a BMI ≥30 kg/m2 than in those with a BMI <30 kg/m2 in both the continuous and intermittent groups. Fewer flares were reported in the continuous treatment group than in the intermittent group in patients with a BMI <30 kg/m2 (0.55 vs 0.88; p<0.0001) and ≥30 kg/m2 (0.54 vs 0.97; p<0.0001). There were no differences in adverse events in the two BMI groups. Conclusions: Continuous celecoxib treatment was significantly more efficacious than intermittent use in patients with a BMI <30 kg/m2 compared with obese patients (≥30 kg/m2) as assessed by WOMAC total scores and the number of flares. These data suggest that including weight loss as part of a treatment regimen for obese OA patients could be important.

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HAPPi Kneecaps! A double-blind, randomised, parallel group superiority trial investigating the effects of sHoe inserts for adolescents with patellofemoral PaIn: phase II feasibility study

Journal of Foot and Ankle Research ◽

10.1186/s13047-021-00498-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Isobel C. O’Sullivan ◽

Kay M. Crossley ◽

Steven J. Kamper ◽

Marienke van Middelkoop ◽

Bill Vicenzino ◽

...

Keyword(s):

Quality Of Life ◽

Recruitment Rate ◽

Full Scale ◽

Trial Registration ◽

Foot Orthoses ◽

Double Blind ◽

Parallel Group ◽

Patient Reported ◽

To Receive

Abstract Background Patellofemoral pain (PFP) affects one-third of adolescents and can persist into adulthood, negatively impacting health and quality of life. Foot orthoses are a recommended treatment for adults with PFP, but have not been evaluated in adolescents. The primary objective was to determine the feasibility of conducting a full-scale randomised controlled trial (RCT) evaluating effects of contoured, prefabricated foot orthoses on knee pain severity and patient-perceived global change, compared to flat insoles. The secondary objective was to describe outcomes on a range of patient-reported outcome measures. Methods We recruited adolescents aged 12–18 years with PFP of ≥2 months duration into a double-blind, randomised, parallel-group feasibility trial. Participants were randomised to receive prefabricated contoured foot orthoses or flat shoe insoles, and followed for 3 months. Participants and outcome assessors were blinded to group allocation. Primary outcomes were feasibility of a full-scale RCT (number of eligible/enrolled volunteers; recruitment rate; adherence with the intervention and logbook completion; adverse effects; success of blinding; drop-out rate), and credibility and expectancy of interventions. Secondary outcomes were patient-reported measures of pain, symptoms, function, quality of life, global rating of change, patient acceptable symptom state, and use of co-interventions. Results 36 out of 279 (12.9%) volunteers (27 female, mean (SD) age 15 (2) years, body mass 60 (13) kg) were eligible and enrolled, at a recruitment rate of 1.2 participants/week. 17 participants were randomised to receive foot orthoses, and 19 to flat insoles. 15 participants returned logbooks; 7/15 (47%) adhered to the intervention. No serious adverse events were reported. 28% (10/36, 4 pandemic-related) of participants dropped out before 3 months. Blinding was successful. Both groups found the inserts to be credible. Conclusions Based on a priori criteria for feasibility, findings suggest that a full-scale RCT comparing contoured foot orthoses to flat insoles in adolescents with PFP would not be feasible using the current protocol. Prior to conducting a full-scale RCT, feasibility issues should be addressed, with protocol modifications to facilitate participant retention, logbook completion and shoe insert wear. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000957190. Date registered: 8/07/2019.

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A Randomized, Placebo-controlled, Double-blind Study on the Effects of SZL on Patients With Mild to Moderate Depressive Disorder With Comparison to Fluoxetine

10.21203/rs.3.rs-70759/v1 ◽

2020 ◽

Author(s):

yuan hu ◽

yichen wang ◽

chao chen ◽

wenshan yang ◽

weiyu zhu ◽

...

Keyword(s):

Depressive Disorder ◽

Depression Scale ◽

Double Blind Study ◽

Double Blind ◽

Moderate Depression ◽

Parallel Group ◽

Clinical Presentations ◽

Significant Difference ◽

To Receive ◽

Target Effects

Abstract Objective: Kaixinsan (KXS) decoction, as an ancient’s herbal formula, has been demonstrated to be active in various animal models resembling human depression with multi-target effects. This very first study evaluated the efficacy and tolerability of Shen Zhi Ling (SZL) tables (KXS preparation), compared with fluoxetine (FLX, positive comparator), in patients with mild to moderate depressive disorder.Methods: In this randomized double-blind parallel-group study, 156 patients with mild to moderate depression without taken any antidepressants in the past 6 months or 4 straight weeks were randomized to receive either 3.2g/d SZL plus 20mg/d FLX placebo (SZL group) or 20mg/d FLX plus 3.2g/d SZL placebo (FLX group), for 8 weeks. Their clinical presentations and some metabolic indexes were assessed during the 8 weeks visiting period.Results: Patients in SZL group showed a statistically significant improvement after 8 weeks of treatment in HAMD-17 score (18.79±2.09 to 4.43±4.71, p<0.001) and self-rating depression scale (SDS) score (58.49±8.89 to 39.84±12.09, p<0.001), but not in N-back total respond time (1145.55±608.26 to 1128.47±387.49, p>0.05). In addition, no significant difference at 8 weeks of treatment was found between SZL and FLX groups in SDS score (39.84±12.09 vs. 36.63±12.44) and N-back respond time (1128.47±387.49 vs. 1089.43±352.08) as well as reduction of HAMD-17 score (14.79±4.88 vs. 15.24±4.29) (p>0.05 for all). However, the serum APOB, APOC3 and ALB levels and HDL-C/LDL-C ratio decreased significantly in patients after SZL treatment, while only APOB/APOA1 ratio decreased significantly in FLX group. Other metabolic indexes did not alter significantly after treated with SZL or FLX.Conclusion: The efficacy and safety profile of SZL are comparable to that of fluoxetine in patients with mild to moderate depression. The beneficial effect of SZL is probably associated with improvement of lipid metabolic balance.

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A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful Improvement in Analgesia after Cesarean Delivery

Anesthesiology ◽

10.1097/aln.0000000000000722 ◽

2015 ◽

Vol 123 (2) ◽

pp. 320-326 ◽

Cited By ~ 33

Author(s):

David T. Monks ◽

David W. Hoppe ◽

Kristi Downey ◽

Vibhuti Shah ◽

Paul Bernstein ◽

...

Keyword(s):

Cesarean Delivery ◽

Analgesic Efficacy ◽

Control Group ◽

Double Blind ◽

Meaningful Improvement ◽

Analgesic Regimen ◽

Parallel Group ◽

Superiority Trial ◽

Perioperative Course ◽

To Receive

Abstract Background: Studies examining the efficacy of a single preoperative dose of gabapentin for analgesia after cesarean delivery (CD) have been inconclusive. The authors hypothesized that a perioperative course of gabapentin would improve analgesia after CD. Methods: This single-center, randomized, double-blind, placebo-controlled, parallel-group, superiority trial was designed to determine the analgesic efficacy of a perioperative course of gabapentin when added to a multimodal analgesic regimen. Women scheduled for elective CD during spinal anesthesia were randomized to receive a perioperative oral course of either gabapentin (600 mg preoperatively followed by 200 mg every 8 h for 2 days) or placebo. Postoperative pain was measured at 24 and 48 h, at rest and on movement, on a visual analogue scale (VAS, 0 to 100 mm). The primary outcome was pain on movement at 24 h. Neonatal outcomes, opiate consumption, VAS satisfaction (0 to 100 mm), adverse effects, and persistent pain were also assessed. Results: Baseline characteristics were similar between groups. There was a statistically significant but small reduction in VAS pain score (mean [95% CI]) on “movement” (40 mm [36 to 45] vs. 47 mm [42 to 51]; difference, −7 mm [−13 to 0]; P = 0.047) at 24 h in the gabapentin (n = 100) compared with control group (n = 97). There was more sedation in the gabapentin group at 24 h (55 vs. 39%, P = 0.026) but greater patient VAS satisfaction (87 vs. 77 mm, P = 0.003). Conclusions: A perioperative course of gabapentin produces a clinically insignificant improvement in analgesia after CD and is associated with a higher incidence of sedation.

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