Clinical Trials Of Novel Therapeutics Research Articles

2015 David Y. Graham Lecture: The First Two Decades Of Eosinophilic Esophagitis-From Acid Reflux To Food Allergy.

Collaborative efforts by pediatric and adult gastroenterologists, allergists, dieticians, and pathologists have brought about marked progress in the recognition, understanding, and management of eosinophilic esophagitis (EoE) over the past two decades. Once an esoteric diagnosis, EoE is now increasingly identified as a major cause of morbidity, afflicting both children and adults. The detection of mucosal eosinophils has evolved from a diagnostic feature of acid reflux to a biomarker of food sensitization of the esophagus. Translational studies and murine models have elucidated Th-2 immune pathways in EoE, inspiring the development of targeted biologic therapeutics. At the same time, validation of patient-reported outcomes and endoscopic end points has facilitated the implementation of clinical trials of novel therapeutics. Ongoing investigations have elucidated the importance of "looking beneath the surface" of the epithelium, focusing greater attention on the impact of esophageal remodeling in the clinical consequences of EoE. Elimination diets continue to gain popularity as an intriguing, highly effective, and non-pharmacologic therapy that lends credence to the concept that EoE is a food-driven, immunologic disorder.

Assessing the feasibility and safety of serial core needle biopsies in multiple early-phase clinical trials.

e22100 Background: The value of early phase clinical trials of novel therapeutics is greatly enhanced through serial tumor biopsies to assess pharmacodynamic markers of drug activity. However, the ...

The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used.

Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials. The Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 individuals, aged 2-28 years, with DMD in a longitudinal, observational study at 20 centers. Assessments obtained every 3 months for 1 year, at 18 months, and annually thereafter included: clinical history; anthropometrics; goniometry; manual muscle testing; quantitative muscle strength; timed function tests; pulmonary function; and patient-reported outcomes/health-related quality-of-life instruments. Glucocorticoid (GC) use at baseline was 62% present, 14% past, and 24% GC-naive. In those ≥6 years of age, 16% lost ambulation over the first 12 months (mean age 10.8 years). Detailed information on the study methodology of the CINRG DMD-NHS lays the groundwork for future analyses of prospective longitudinal natural history data. These data will assist investigators in designing clinical trials of novel therapeutics.

Calcium ion channels: challenges and successes in drug discovery

AbstractThere are both opportunities and challenges in developing improved or novel therapeutics based on targeting voltage‐gated calcium channels. Calcium channels are technically difficult with respect to target‐based drug discovery but unquestionably are key points for influencing human physiology and pathophysiology. Many marketed drugs, including nifedipine, nimodipine, ethosuximide, pregabalin, and ziconotide, exert therapeutic efficacy via inhibition of calcium channels. Although there is no obvious path to improving these existing drugs, recent clinical results with dihydropyridine drugs point to testable strategies for treatment of Parkinson's disease and possibly other CNS disorders by inhibiting L‐type calcium channels. Roles of T‐type calcium channels in pain and in abnormal sleep are plausible and may soon be tested with clinical trials of novel therapeutics. Success with any of these trials certainly will be followed by intensive efforts for further refinements around the target class. WIREs Membr Transp Signal 2013, 2:85–104. doi: 10.1002/wmts.71For further resources related to this article, please visit the WIREs website.

MRI in Lower Extremity Peripheral Arterial Disease: Recent Advancements.

Evaluation of peripheral arterial disease by cardiovascular magnetic resonance imaging continues to develop. Of the clinical diagnostics tests currently available, magnetic resonance angiography is well established as one of the preferred techniques for determining areas of arterial occlusive disease affecting the lower extremities. Despite this, there have been new developments in non-gadolinium based contrast-enhanced studies as well as testing done at higher field strength scanners. In the research arena, magnetic resonance spectroscopy, calf muscle perfusion imaging and atherosclerotic plaque evaluation all have made significant advancements over the last year. These techniques are gaining traction as surrogate endpoints in clinical trials of novel therapeutics aimed at alleviating symptoms in patients with peripheral arterial disease.

Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [(15)O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. Key Points • [ ( 15 ) O]-water is the gold standard for blood flow/tissue perfusion with PET • In some instances dynamic [ ( 18 ) F]-FDG uptake may be used to estimate perfusion • Radiopharmaceuticals that target integrins are now being evaluated for measuring tumour vascularity.

A Blueprint for Advancing Genetics-Based Cancer Therapy

In the era of next-generation sequencing, there are significant challenges to harnessing cancer genome information to develop novel therapies. Key research thrusts in both academia and industry will speed this transition, and lessons learned for cancer will more broadly shape the process for genetic contributions to the therapy of disease more broadly.

How will Lung Cancer be Treated in the Future?

Lung cancer is still considered the leading cause of cancer-related deaths in industrialized countries. Despite improvements in cancer diagnosis and therapy, the present 5-year survival rate of 14% is only slightly higher than the survival rate of 8% in the early 1960s. At present, a survival plateau has been reached by the current management of lung cancer, including surgery, chemo- and radiotherapy. Although prevention and early diagnosis are undoubtedly important, more innovative treatment approaches and new agents that affect alternate mechanisms in tumor cells are needed. Since molecular targets of tumorigenesis and metastasis are currently the focus of lung cancer research, this review will summarize the most important molecular approaches and clinical trials of novel therapeutics.