scholarly journals The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study

2004 ◽  
Vol 80 (6) ◽  
pp. 1658-1664 ◽  
Author(s):  
Yoram Bouhnik ◽  
Laurent Raskine ◽  
Guy Simoneau ◽  
Eric Vicaut ◽  
Christel Neut ◽  
...  
Keyword(s):  
Dose Response ◽  
Double Blind ◽  
Healthy Humans ◽  
Parallel Group

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

SLEEP ◽  
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):

34Efficacy and safety of various doses of the new dual endothelin receptor antagonist aprocitentan in the treatment of hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Danaietash ◽  
P Verweij ◽  
B Flamion ◽  
J Menard ◽  
M Bellet
Keyword(s):  
Dose Response ◽  
Study Drug ◽  
Positive Control ◽  
Digital Ulcers ◽  
Maximal Effect ◽  
Endothelin Receptor ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Parallel Group ◽  
Treatment Of Hypertension

Abstract Background Endothelin Receptor Antagonists (ERAs) have been investigated for the treatment of a variety of cardiovascular conditions because of their potent vasodilating properties. However, until now, ERAs have only been registered for the treatment of pulmonary arterial hypertension and scleroderma-induced digital ulcers. This class of drugs may also be useful in the treatment of difficult to control hypertension with a medical need. Purpose To investigate the efficacy and safety of various doses of the new dual ERA, aprocitentan, in the treatment of hypertension in order to determine the most appropriate dose(s) for further clinical development using an unattended, automated office BP (AOBP) device (BpTRU). This Phase 2 trial was registered at ClinicalTrials.gov [NCT02603809]. Methods Eligible patients with hypertension (mean sitting systolic/diastolic BP 149.7/97.6 mmHg) received aprocitentan 5, 10, 25 or 50 mg, matching placebo or lisinopril 20 mg as a positive control, once daily for 8 weeks using a randomised, double-blind, parallel-group study design. AOBP was assessed at baseline and weeks 2, 4, 8, and 10 (withdrawal) by recording multiple BP readings with the patient resting quietly. Additionally, 24 h ambulatory BP monitoring was performed at baseline and week 8. Results A total of 490 eligible patients were randomised to the double-blind phase with 430 subjects successfully completing 8 weeks of treatment. Decreases in sitting systolic/diastolic AOBP, from baseline to week 8 were 10.3/6.3, 15.0/9.9, 18.5/12.0 and 15.1/10.0 mmHg for aprocitentan 5, 10, 25, and 50 mg, respectively vs. 7.7/4.9 mmHg for placebo and 12.8/8.4 mmHg for lisinopril. No changes in heart rate or body weight were observed for any dose of aprocitentan. Modelling the dose-response suggested that the maximal effect of aprocitentan is achieved at a dose of approximately 25 mg and that 70% of this effect is already observed at a dose of 10 mg. Aprocitentan treatment was associated with decreases in haemoglobin, haematocrit, and albumin which exhibited a monotonic dose-response relationship, in line with its known vasodilating effects. Estimated increases in plasma volume were 3.0%, 5.1%, 6.9%, and 9.5% for aprocitentan 5, 10, 25, and 50 mg, respectively, vs. 1.6% for lisinopril and a decrease of 0.3% for placebo. All these values are below the accepted pathophysiological threshold of 10%. The overall incidence of adverse events observed in the aprocitentan groups (ranging from 22.0% to 40.2%) was similar to that seen in the placebo group (36.6%). Overall, the most common events were hypertension, headache, and nasopharyngitis. Conclusions These findings support the use of aprocitentan at doses between 10 and 25 mg for further investigation as a potential treatment for hypertension. Acknowledgement/Funding Actelion conducted study. Drug discovery & early clinical pipeline demerged during Johnson & Johnson acquisition. Idorsia supported abstract.

scholarly journals Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double blind dose response study in Lagos

2021 ◽  
Author(s):  
OE Babalola ◽  
CO Bode ◽  
AA Ajayi ◽  
FM Alakaloko ◽  
IE Akase ◽  
...  
Keyword(s):  
Platelet Count ◽  
Dose Response ◽  
Repeated Measures ◽  
Standard Of Care ◽  
Double Blind ◽  
Parallel Group ◽  
Clinical Benefits ◽  
Randomised Controlled

ABSTRACTIntroductionIn vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV-2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.MethodsWe conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.ResultsThe Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/−5.2, for A 6.0 +/− 2.9, and for B 4.6 +/−3.2. 2 Way repeated measures ANOVA of ranked COVID 19 + / − scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p=0.035) and time effect (p <0.0001). IV also tended to increase SPO2 % compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = −0.52, p = 0.005). No SAE was reported.Conclusions12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.

scholarly journals The ISAD (Infraslow Neurofeedback for Anxiety and Depression) Study: A Protocol for a Trans-Diagnostic, Randomized, Double-Blind, Sham-Controlled, Dose-Response, Parallel-Group Trial

2021 ◽  
Author(s):  
Tyson Perez ◽  
Paul Glue ◽  
Divya B Adhia ◽  
Mark Smith ◽  
Dirk De Ridder ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Dose Response ◽  
Electrodermal Activity ◽  
Physiological Measures ◽  
Double Blind ◽  
The Core ◽  
Parallel Group ◽  
Patient Reported ◽  
Parallel Group Trial ◽  
Group Trial

Abstract Background: The core intrinsic connectivity networks (ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individual’s with internalizing disorders (IDs; e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localised electroencephalogram neurofeedback (EEG-NFB) therapy targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a transdiagnostic, randomized, double-blind, sham-controlled, dose-response, parallel-group trial of standardized low-resolution electromagnetic tomography electrophysiological infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA eISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary aim will be to assess the clinical efficacy of sLORETA eISF-NFB via relevant patient-reported outcomes (PROs). Methods: We will randomly assign participants with a current diagnosis of MDD, GAD, and/or SOC to one of four groups: 1) 12 sessions of posterior cingulate cortex (PCC) up-training (n=15), 2) 6 sessions of yoked-sham training followed by 6 sessions of PCC up-training (n=15), 3) 12 sessions of concurrent mid-cingulate (MCC) down-training and PCC up-training (n=15), or 4) 6 sessions of yoked-sham training followed by 6 sessions of concurrent MCC down-training and PCC up-training. Transdiagnostic PROs, as well as resting-state neuro-physiological measures (EEG; electrocardiography, ECG; electrodermal activity, EDA), will be collected from all subjects at baseline, mid-training, 1 week post-training, and 1 month post-training. We will further compare baseline PROs and neuro-physiological measures to age- and sex-matched non-ID (i.e. no ID diagnosis) controls. Discussion: This protocol will outline the rationale and research methodology for a clinical trial of sLORETA eISF-NFB targeting key nodes within the core ICNs in a population with IDs with the primary aim being to assess its specific (e.g. non-placebo induced) efficacy via PROs. Trial Registration: Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial Id: ACTRN12619001428156)

Fructose intolerance: A randomized, double blind, dose response study in healthy humans

2003 ◽  
Vol 124 (4) ◽  
pp. A43
Author(s):  
Leslie Anderson ◽  
Joan Kempf ◽  
Phyllis Stumbo ◽  
Satish Rao
Keyword(s):  
Dose Response ◽  
Double Blind ◽  
Healthy Humans ◽  
Fructose Intolerance ◽  
Dose Response Study

scholarly journals Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos

QJM ◽  
2021 ◽  
Author(s):  
O E Babalola ◽  
C O Bode ◽  
A A Ajayi ◽  
F M Alakaloko ◽  
I E Akase ◽  
...  
Keyword(s):  
Platelet Count ◽  
Dose Response ◽  
Repeated Measures ◽  
Standard Of Care ◽  
Double Blind ◽  
Parallel Group ◽  
Clinical Benefits ◽  
Randomised Controlled

Abstract Introduction In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV- 2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19. Methods We conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care. Results The Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/-5.2, for A 6.0 +/- 2.9, and for B 4.6 +/-3.2 . 2 Way repeated measures ANOVA of ranked COVID 19 +/- scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p = 0.035) and time effect (p &lt; 0.0001). IV also tended to increase SPO2% compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = -0.52, p = 0.005). No SAE was reported. Conclusions 12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karolina Samekova ◽  
Christa Firbas ◽  
Johanna Irrgeher ◽  
Christine Opper ◽  
Thomas Prohaska ◽  
...  
Keyword(s):  
Oral Intake ◽  
Blood Lead ◽  
Organ Damage ◽  
Lead Uptake ◽  
Double Blind ◽  
Total Blood ◽  
Healthy Humans ◽  
Parallel Group ◽  
To Receive ◽  
Clinoptilolite Tuff

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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