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Proof of concept Phase I or Phase II clinic trial

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https://www.readbyqxmd.com/read/29177955/a-randomized-double-blind-placebo-controlled-proof-of-concept-trial-of-creatine-monohydrate-as-adjunctive-treatment-for-bipolar-depression
#1
Ricardo Alexandre Toniolo, Michelle Silva, Francy de Brito Ferreira Fernandes, José Antonio de Mello Siqueira Amaral, Rodrigo da Silva Dias, Beny Lafer
Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder. Currently available treatments for this condition have limited efficacy and new therapeutic options are needed. Extensive research in the pathophysiology of bipolar disorder points to the existence of mitochondrial and bioenergetic dysfunction. We hypothesized that creatine monohydrate, a nutraceutical that works as a mitochondrial modulator, would be effective as an adjunctive therapy for bipolar depression...
November 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29132229/hyperbaric-oxygen-therapy-in-the-treatment-of-acute-severe-traumatic-brain-injury-a-systematic-review
#2
Samuel Daly, Maxwell Thorpe, Sarah B Rockswold, Molly Hubbard, Thomas A Bergman, Uzma Samadani, Gaylan Rockswold
There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO2) in the context of an impending National Institute of Neurologic Disorders and Stroke (NINDS)-funded, multicenter, randomized, adaptive Phase II clinical trial - the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (8 clinical and 22 pre-clinical) that administered HBO2 within 30 days of a TBI were identified from PubMed searches...
November 13, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29089466/preclinical-and-clinical-advances-in-transposon-based-gene-therapy
#3
Jaitip Tipanee, Yoke Chin Chai, Thierry VandenDriessche, Marinee K Chuah
Transposons derived from Sleeping Beauty (SB), piggyBac (PB) or Tol2 typically require cotransfection of transposon DNA with a transposase either as an expression plasmid or mRNA. Consequently, this results in genomic integration of the potentially therapeutic gene into chromosomes of the desired target cells and thus conferring stable expression. Nonviral transfection methods are typically preferred to deliver the transposon components in to the target cells. However, these methods do not match the efficacy typically attained with viral vectors and are sometimes associated with cellular toxicity evoked by the DNA itself...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29067332/ub-311-a-novel-ubith-%C3%A2-amyloid-%C3%AE-peptide-vaccine-for-mild%C3%A2-alzheimer-s%C3%A2-disease
#4
Chang Yi Wang, Pei-Ning Wang, Ming-Jang Chiu, Connie L Finstad, Feng Lin, Shugene Lynn, Yuan-Hung Tai, Xin De Fang, Kesheng Zhao, Chung-Ho Hung, Yiting Tseng, Wen-Jiun Peng, Jason Wang, Chih-Chieh Yu, Be-Sheng Kuo, Paul A Frohna
INTRODUCTION: A novel amyloid β (Aβ) synthetic peptide vaccine (UB-311) has been evaluated in a first-in-human trial with patients of mild-to-moderate Alzheimer's disease. We describe translational research covering vaccine design, preclinical characterization, and phase-I clinical trial with supportive outcome that advances UB-311 into an ongoing phase-II trial. METHODS: UB-311 is constructed with two synthetic Aβ1-14-targeting peptides (B-cell epitope), each linked to different helper T-cell peptide epitopes (UBITh(®)) and formulated in a Th2-biased delivery system...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29052441/investigational-glucagon-receptor-antagonists-in-phase-i-and-ii-clinical-trials-for-diabetes
#5
André J Scheen, Nicolas Paquot, Pierre J Lefèbvre
Despite type 2 diabetes (T2D) being recognized as a bihormonal pancreatic disease, current therapies are mainly focusing on insulin, while targeting glucagon has been long dismissed. However, glucagon receptor (GCGr) antagonists are currently investigated in clinical trials. Area covered: Following a brief description of the rationale for antagonizing GCGr in T2D, lessons from GCGr knock-out mice and pharmacological means to antagonize GCGr, a detailed description of the main results obtained with GCGr antagonists in Phase I-II clinical trials is provided...
October 26, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29019353/hot-news-ready-for-hiv-dual-therapy-new-data-from-international-hiv-aids-society-2017
#6
George A Yendewa, Robert A Salata
The introduction of combination antiretroviral therapy (ART) in the 1990s has fundamentally transformed the landscape of HIV medicine, greatly improved disease morbidity and mortality, and reduced transmission rates across all demographic groups. Central to this success was the idea that to achieve best disease outcomes and minimize the development of drug resistance, at least three antiretroviral agents should be used for HIV treatment. This therapeutic strategy is a core tenet of HIV medicine, backed by incontrovertible scientific evidence, and made easy to deploy by the high compliance levels with once-daily coformulations, which have generally been well tolerated...
October 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28851316/a-non-controlled-single-arm-open-label-phase-ii-study-of-intravenous-and-intratumoral-administration-of-parvoryx-in-patients-with-metastatic-inoperable-pancreatic-cancer-parvoryx02-protocol
#7
Jacek Hajda, Monika Lehmann, Ottheinz Krebs, Meinhard Kieser, Karsten Geletneky, Dirk Jäger, Michael Dahm, Bernard Huber, Tilman Schöning, Oliver Sedlaczek, Albrecht Stenzinger, Niels Halama, Volker Daniel, Barbara Leuchs, Assia Angelova, Jean Rommelaere, Christine E Engeland, Christoph Springfeld, Guy Ungerechts
BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy...
August 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28830912/mapping-genetic-vulnerabilities-reveals-btk-as-a-novel-therapeutic-target-in-oesophageal-cancer
#8
Irene Yushing Chong, Lauren Aronson, Hanna Bryant, Aditi Gulati, James Campbell, Richard Elliott, Stephen Pettitt, Paul Wilkerson, Maryou B Lambros, Jorge S Reis-Filho, Anisha Ramessur, Michael Davidson, Ian Chau, David Cunningham, Alan Ashworth, Christopher J Lord
OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations...
August 22, 2017: Gut
https://www.readbyqxmd.com/read/28798986/a-phase-ii-multicentre-open-label-proof-of-concept-study-of-tasquinimod-in-hepatocellular-ovarian-renal-cell-and-gastric-cancers
#9
Bernard Escudier, Sandrine Faivre, Eric Van Cutsem, Nathalie Germann, Jean-Christophe Pouget, Ruth Plummer, Ignace Vergote, Fiona Thistlethwaite, Georg A Bjarnason, Robert Jones, Helen Mackay, Julien Edeline, Laetitia Fartoux, Hal Hirte, Amit Oza
BACKGROUND: Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. PATIENTS AND METHODS: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers...
October 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28767654/cancer-stem-cell-related-gene-expression-as-a-potential-biomarker-of-response-for-first-in-class-imipridone-onc201-in-solid-tumors
#10
Varun V Prabhu, Amriti R Lulla, Neel S Madhukar, Marie D Ralff, Dan Zhao, Christina Leah B Kline, A Pieter J Van den Heuvel, Avital Lev, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Tracy T Batchelor, Andrew S Chi, Olivier Elemento, Joshua E Allen, Wafik S El-Deiry
Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction...
2017: PloS One
https://www.readbyqxmd.com/read/28760486/a-novel-brain-computer-interface-for-classification-of-social-joint-attention-in-autism-and-comparison-of-3-experimental-setups-a-feasibility-study
#11
Carlos P Amaral, Marco A Simões, Susana Mouga, João Andrade, Miguel Castelo-Branco
BACKGROUND: We present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD). NEW METHOD: We tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems...
July 29, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28738857/investigating-interventions-to-increase-uptake-of-hiv-testing-and-linkage-into-care-or-prevention-for-male-partners-of-pregnant-women-in-antenatal-clinics-in-blantyre-malawi-study-protocol-for-a-cluster-randomised-trial
#12
Augustine T Choko, Katherine Fielding, Nigel Stallard, Hendramoorthy Maheswaran, Aurelia Lepine, Nicola Desmond, Moses K Kumwenda, Elizabeth L Corbett
BACKGROUND: Despite large-scale efforts to diagnose people living with HIV, 54% remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and uptake of follow-on services remains wide with much lower rates of HIV testing among men compared to women. Here, we design a study to investigate the effect on uptake of HIV testing and linkage into care or prevention of partner-delivered HIV self-testing alone or with an additional intervention among male partners of pregnant women...
July 24, 2017: Trials
https://www.readbyqxmd.com/read/28738565/zwitterionic-hydrophilic-interaction-liquid-chromatography-tandem-mass-spectrometry-with-hybridspe-precipitation-for-the-determination-of-intact-cisplatin-in-human-plasma
#13
Feifan Xie, Pieter Colin, Jan Van Bocxlaer
Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial...
November 1, 2017: Talanta
https://www.readbyqxmd.com/read/28582570/phase-ii-proof-of-concept-trial-of-the-orexin-receptor-antagonist-filorexant-mk-6096-in-patients-with-major-depressive-disorder
#14
Kathryn M Connor, Paulette Ceesay, Jill Hutzelmann, Duane Snavely, Andrew D Krystal, Madhukar H Trivedi, Michael Thase, Christopher Lines, W Joseph Herring, David Michelson
Background: We evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder. Methods: We conducted a 6-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with major depressive disorder (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10 mg or matching placebo. Results: Due to enrollment challenges, the study was terminated early, resulting in insufficient statistical power to detect a prespecified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment...
August 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28450365/critical-issues-for-the-translation-of-cardioprotection
#15
REVIEW
Gerd Heusch
The translation from numerous successful animal experiments on cardioprotection beyond that by reperfusion to clinical practice has to date been disappointing. Animal experiments often use reductionist approaches and are mostly performed in young and healthy animals which lack the risk factors, comorbidities, and comedications which are characteristics of patients suffering an acute myocardial infarction or undergoing cardiovascular surgery. Conceptually, it is still unclear by how much the time window for successful reperfusion is extended by preconditioning, and how long the duration of ischemia can be so that adjunct cardioprotection by postconditioning at reperfusion still protects...
April 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/28372596/a-proof-of-concept-investigation-into-ketamine-as-a-pharmacological-treatment-for-alcohol-dependence-study-protocol-for-a-randomised-controlled-trial
#16
Amy McAndrew, Will Lawn, Tobias Stevens, Lilla Porffy, Brigitta Brandner, Celia J A Morgan
BACKGROUND: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group...
April 4, 2017: Trials
https://www.readbyqxmd.com/read/28318420/bayesian-penalized-log-likelihood-ratio-approach-for-dose-response-clinical-trial-studies
#17
Yuanyuan Tang, Chunyan Cai, Liangrui Sun, Jianghua He
In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further develop an alternative approach in a Bayesian framework based on the posterior distribution of a penalized log-likelihood ratio test statistic. Our Bayesian approach is much more flexible to handle linear or nonlinear dose-response relationships and is more efficient than the permutation approach...
February 13, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28174390/-surgical-regeneration-therapy-using-myoblast-sheets-for-severe-heart-failure
#18
Yoshiki Sawa
Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#19
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
June 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/27980779/distinct-immunological-activation-profiles-of-dslim%C3%A2-and-promune%C3%A2-depend-on-their-different-structural-context
#20
Kerstin Kapp, Jacqueline Schneider, Lisa Schneider, Nadine Gollinge, Stefanie Jänsch, Matthias Schroff, Burghardt Wittig, Christiane Kleuss
INTRODUCTION: DNA-based TLR9 agonists are potent activators of the immune system. ProMune® and dSLIM® belong to different families of TLR9 agonists and both have been established as cancer immunotherapeutics in clinical proof-of-concept studies. Unfortunately, ProMune® failed in pivotal oncological trials. dSLIM®, the active ingredient of Lefitolimod (MGN1703), successfully finished a double-blinded, placebo-controlled phase II study in patients with advanced colorectal cancer, exhibiting improved progression-free survival and durable disease control...
December 2016: Immunity, Inflammation and Disease
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