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I Trials (i + trials)
Selected AbstractsGene therapy in epilepsyEPILEPSIA, Issue 1 2009Véronique Riban Summary Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy-based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno-associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long-term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson's disease with an excellent safety profile. Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronic models of epileptogenesis, as well as assessment of safety in toxicological studies. [source] EFNS guidelines on pharmacological treatment of neuropathic painEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006N. Attal Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools. [source] Unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunctionNEUROUROLOGY AND URODYNAMICS, Issue 8 2008Khanh Pham Abstract Aims To determine if bilateral S3 lead placement during the stage I trial period improves the "success" rate for advancing to stage II (permanent) sacral neuromodulator placement. Methods A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim®, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall "success", defined as progression from stage I to stage II placement. Results Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P,=,0.03). Five wound infections were reported,2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered. Conclusions Bilateral stage I neuromodulation trial provides a significantly higher rate of improvement in refractory voiding symptoms to allow for the progress to stage II implantation. Neurourol. Urodynam. 27:779,781, 2008, © 2008 Wiley-Liss, Inc. [source] Dose Finding for Continuous and Ordinal Outcomes with a Monotone Objective Function: A Unified ApproachBIOMETRICS, Issue 1 2009Anastasia Ivanova Summary In many phase I trials, the design goal is to find the dose associated with a certain target toxicity rate. In some trials, the goal can be to find the dose with a certain weighted sum of rates of various toxicity grades. For others, the goal is to find the dose with a certain mean value of a continuous response. In this article, we describe a dose-finding design that can be used in any of the dose-finding trials described above, trials where the target dose is defined as the dose at which a certain monotone function of the dose is a prespecified value. At each step of the proposed design, the normalized difference between the current dose and the target is computed. If that difference is close to zero, the dose is repeated. Otherwise, the dose is increased or decreased, depending on the sign of the difference. [source] In vivo manipulation of V,9V,2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patientsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010S. Meraviglia Summary The potent anti-tumour activities of ,, T cells have prompted the development of protocols in which ,,-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V,9V,2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V,9V,2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral V,9V,2 T cell numbers emerged, as seven patients who failed to sustain V,9V,2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral V,9V,2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of V,9V,2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer. [source] | ||||||||||