Browsing by Subject "clinical trials"

Now showing 1 - 10 of 22
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    Asian American women's perspectives on donating healthy breast tissue: implications for recruitment methods and messaging
    (2016-12) Ridley-Merriweather, Katherine E.; Parrish-Sprowl, John; Bute, Jennifer J.; Head, Katharine J.
    Asian women have a lower risk than Caucasians, African Americans, and Latinas of developing breast cancer (BC). Yet, once Asians move to the U.S. their risk rates measurably increase. The Susan G. Komen® Tissue Bank at the IU Simon Cancer Center (KTB), the only biobank of its kind in the world, collects healthy breast tissue from women of all racial groups to use as controls in BC research. The KTB represents a critical tool in efforts to treat and prevent BC; however, Asian American (AA) women display marked reticence towards donating tissue to the KTB. The purpose of this study is to use the basic components of Grounded Practical Theory to explore potential messaging that may result in AAs’ more positive outlook on breast tissue donation. This study recruited seventeen (N=17) AA women to share their perspectives on donating breast tissue for research purposes. Participants took part in an interactive focus group exploring potential messaging for successfully recruiting AA women to the KTB study. Findings revealed that: a) participants retained a culturally-embedded discomfort with donating, and a general distrust that their donation would be handled ethically and appropriately; b) the women possessed an extraordinary need for knowledge about all facets of the donation process; c) participants perceived that they lack a personal connection to BC, making it difficult for them to generate any truly altruistic tendencies to perform the desired behavior, or to understand a need to do so; and d) they possess a strong desire to learn why it seems important to the KTB to collect their tissue, and especially about the increased BC rates and risk for Asians who move to or are born in the U.S. The findings from this study have important implications for others who work in applied clinical settings and are interested in addressing racial disparities in medical research through more effective and targeted recruitment messaging.
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    CELLULAR THERAPY AND HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CANCER
    (Office of the Vice Chancellor for Research, 2010-04-09) Farag, Sherif S.; Srivastava, Shivani; Schwartz, Jennifer; Nelson, Robert; Homsi, Yasser; Zhang, Shuhong; Dinauer, Mary; Cornetta, Kenneth; March, Kieth; Pelus, Louis; Broxmeyer, Hal
    The Center for Cellular Therapy and Hematopoietic Stem Cell Transplantation for Cancer was established in July 2007 to promote translational and clinical research in cellular therapy for cancer. The primary goal of the Center is translate discoveries from bench-to-clinic through phase I and early phase II cellular therapy clinical trials. To achieve this objective, the Center has brought together the unique expertise in hematopoiesis, immunology, gene therapy, graft engineering, and clinical hematopoietic stem cell transplantation (HCT) available at IUPUI. Since its establishment, we have completed two phase I clinical trials developing novel preparative regimens for allogeneic and autologous stem cell transplantation for patients with refractory leukemia and lymphoma, respectively. In addition, we have also initiated 5 additional early phase clinical trials that directly translate IUPUI laboratory discoveries to patients with hematological cancers. The Center has successfully competed for external funding through peerreviewed grants and pharmaceutical contracts. In this presentation, we highlight some important examples of the Center’s ongoing and completed research. An important clinical research focus of our Center is the ability to extend the curative potential of allogeneic HCT to patients without suitably HLA-matched donors. We are currently exploring ways to improve the outcomes of umbilical cord blood (UCB) and haplotype-mismatched stem cell transplantation for patients with hematological cancers. The discovery in Dr. Broxmeyer’s Laboratory, Indiana University, Indianapolis, that inhibition of the enzyme CD26 promotes homing and engraftment of limiting numbers of UCB stem cells has been translated to the first clinical trial in vivo CD26 inhibition using sitagliptin in adult leukemia patients undergoing UCB transplantation. Our preliminary data indicates that high-dose sitagliptin is well tolerated and appears to shorten the time of engraftment. As our data is further confirmed in this pilot study, we plan to investigate this potentially paradigm changing approach in a larger national study. As an extension of this research, Dr. Pelus’ Laboratory, Indiana University, Indianapolis, has shown that short-term ex vivo treatment of hematopoietic progenitors using PGE2 will also promote engraftment. We are currently investigating the potential synergy of PGE2 treatment with CD26 inhibition to further enhance engraftment, which if results appear promising will also be translated to a phase I clinical trial. In haplotypemismatched allogeneic HCT, mismatching of donor KIR receptors on natural killer (NK) cells with recipient KIR ligands expressed on the patient’s tumor cells exerts a NK cell-mediated antileukemia effect that contributes to reduced relapse after transplantation. We (Dr. Farag’s Laboratory, Indiana University, Indianapolis) have shown that in vivo donor derived NK cells developing from donor stem cells have an “inhibitory” receptor phenotype that may suboptimally function against leukemia. This has resulted in a phase I trial of purified NK cell infusion following mismatched HCT to investigate the feasibility and safety of this approach, as a prelude to a larger study to investigate its efficacy. Although the highest dose level of NK cells has not yet been investigated, the preliminary data indicates that such a novel approach is feasible. In additional studies based on our laboratory findings, we are exploring the harnessing of NK cells in the therapy of cancer through the monoclonal antibodies that block KIR receptors in combination with immuno-modulatory agents (e.g., lenalidomide) and antibodies that promote antibody-dependent cellular cytotoxicity (e.g., rituximab, anti-CS1). We have initiated patents for these discoveries, and are currently planning to transplant these into phase I clinical trials. Other ongoing research includes enhancing immune function against cancer through STAT3 inhibition to overcome tumor-mediated impairment of dendritic cell maturation, ex vivo specific expansion of cytotoxic of NK cell subsets for clinical use, and enhancing immune cell function following transplantation. The continued success of our Center will depend on a continuing pipeline of novel laboratory discoveries and their translation to early phase clinical trials to assess feasibility and safety as a prelude to larger trials assessing efficacy. Initial funding of the Center by IUPUI has allowed the Center’s conception, and the bringing together of basic and clinical researchers to the “research table” to make this translational/clinical research endeavor a reality, and has allowed us to be competitive for external funding. An important developing outcome of this initiative is the preparation for a Program Project grant in Mobilization and Engraftment of Stem Cells.
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    Clinical performance of intentionally tilted implants versus axially positioned implants: A systematic review
    (Wiley, 2018-10) Lin, Wei-Shao; Eckert, Steven E.; Prosthodontics, School of Dentistry
    Objectives The aim of this review was to determine the clinical performance of dental implants that are intentionally tilted when compared with implants that are placed following the long axis of the residual alveolar ridge. Materials and methods A systematic review of the scientific literature using a predefined research question (PICO) and search strategy was undertaken. This search included five electronic databases. Two independent reviewers examined electronic databases and performed a manual review following search strategy to accomplish the item generation and reduction. Included articles were evaluated to determine the level of evidence. Data were extracted only from level I and level II studies, based on the Oxford Centre for Evidence‐based Medicine—Levels of Evidence (March 2009). If included studies were homogeneous in nature, data were to be accumulated. However, if included studies were heterogeneous in nature, only descriptive data would be reviewed and analyzed. Results A total of 811 articles were identified through the PICO question and search strategy. Detailed review of the abstracts and articles resulted in further item reduction, and 46 articles were included for full‐text review. A total of 42 articles were then selected for inclusion in the systematic review. The identified articles included two level I and 20 level II studies. In addition, 15 level IV, one gray literature, and four previous systematic reviews with meta‐analyses were also used in the study. The extracted data from the included studies demonstrated heterogeneity that prevented quantitative assessment, and only one level II study directly compared tilted and axially placed implants. Assessment of the descriptive data demonstrated no differences in implant survival, marginal bone loss, prosthesis survival, or patient‐reported outcome measures (PROMs) whether implants are placed axially or with intentional inclination of the coronal aspect of the implant toward the distal aspect of edentulous jaws. Conclusions Based upon the systematic review of the literature, an analysis of the descriptive data suggested no differences in clinical performance between implants that are placed in an axial position relative to the residual alveolar ridge when compared with implants that are intentionally tilted toward the distal aspect of edentulous jaws.
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    Combination Immunotherapy for Type 1 Diabetes
    (Springer, 2017-07) Bone, Robert N.; Evans-Molina, Carmella; Medicine, School of Medicine
    Purpose of Review Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D. Recent Findings Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. Summary A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.
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    Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma
    (MDPI, 2020-06-02) Mollica, Veronica; Rizzo, Alessandro; Montironi, Rodolfo; Cheng, Liang; Giunchi, Francesca; Schiavina, Riccardo; Santoni, Matteo; Fiorentino, Michelangelo; Lopez-Beltran, Antonio; Brunocilla, Eugenio; Brandi, Giovanni; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
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    Defining end-stage renal disease in clinical trials: a framework for adjudication
    (Oxford, 2016-06) Agarwal, Rajiv; Department of Medicine, IU School of Medicine
    Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m2 itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease.
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    Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS)
    (Elsevier, 2021) Ma, Christopher; Schoepfer, Alain M.; Dellon, Evan S.; Bredenoord, Albert J.; Chehade, Mirna; Collins, Margaret H.; Feagan, Brian G.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Jairath, Vipul; Katzka, David A.; Pai, Rish K.; Rothenberg, Marc E.; Straumann, Alex; Aceves, Seema S.; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Biedermann, Luc; Blanchard, Carine; Cianferoni, Antonella; Ciriza de los Rios, Constanza; Clayton, Frederic; Davis, Carla M.; de Bortoli, Nicola; Dias, Jorge A.; Falk, Gary W.; Genta, Robert M.; Ghaffari, Gisoo; Gonsalves, Nirmala; Greuter, Thomas; Hopp, Russell; Hsu Blatman, Karen S.; Jensen, Elizabeth T.; Johnston, Doug; Kagalwalla, Amir F.; Larsson, Helen M.; Leung, John; Louis, Hubert; Masterson, Joanne C.; Menard-Katcher, Calies; Menard-Katcher, Paul A.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Penagini, Roberto; Pesek, Robert D.; Peterson, Kathryn; Putnam, Philip E.; Ravelli, Alberto; Savarino, Edoardo V.; Schlag, Christoph; Schreiner, Philipp; Simon, Dagmar; Smyrk, Thomas C.; Spergel, Jonathan M.; Taft, Tiffany H.; Terreehorst, Ingrid; Vanuytsel, Tim; Venter, Carina; Vieira, Mario C.; Vieth, Michael; Vlieg-Boerstra, Berber; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Woodland, Philip; Woosley, John T.; Yang, Guang-Yu; Zevit, Noam; Safroneeva, Ekaterina; Medicine, School of Medicine
    Background End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. Objective We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Methods Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. Results The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. Conclusions This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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    Drug Development for Cystic Fibrosis
    (Wiley, 2021-02) Sanders, Don; Chmiel, James; Pediatrics, School of Medicine
    The first regulatory approval for a drug developed specifically for cystic fibrosis (CF) occurred in 1993, and since then, several other drugs have been approved. Median predicted survival in people with CF in the United States has increased from approximately 30 years to 44.4 years over that same period. Highly effective modulators of the cystic fibrosis transmembrane conductance regulator became available to approximately 90% of people with CF ages 12 years and older in the United States in 2019 and in Europe in 2020. These transformative therapies will surely reduce morbidity and further extend longevity. The drug development pipeline is filled with therapies that address most aspects of CF disease. As survival and CF therapies advance, and the complexity of CF care increases, the process of drug development has become more sophisticated. In addition, detecting meaningful changes in outcome measures has become more difficult as the health status of people with CF improves. Innovative approaches are required to continue to advance drug development in CF. This review provides a general overview of drug development from the preclinical phase through Phase IV. Special considerations with respect to CF are integrated into the discussion of each phase of drug development. As CF care evolves, drug development must continue to evolve as well, until a one-time cure is available to all people with CF.
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    Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration
    (American Academy of Neurology (AAN), 2016-09-20) Wolz, Robin; Schwarz, Adam J.; Gray, Katherine R.; Yu, Peng; Hill, Derek L.G.; Radiology and Imaging Sciences, School of Medicine
    Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population.
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    Ensuring Treatment Fidelity in a Multi-site Behavioral Intervention Study: Implementing NIH Behavior Change Consortium Recommendations in the SMART Trial
    (2011-11) Robb, Sheri L.; Burns, Debra S.; Docherty, Sharron L.; Haase, Joan E.
    The Stories and Music for Adolescent/Young Adult Resilience during Transplant (SMART) study (R01NR008583; U10CA098543; U10CA095861) is an ongoing multi-site Children’s Oncology Group randomized clinical trial testing the efficacy of a therapeutic music video intervention for adolescents/young adults (11–24 years of age) with cancer undergoing stem cell transplant. Treatment fidelity strategies from our trial are consistent with the NIH Behavior Change Consortium Treatment Fidelity Workgroup (BCC) recommendations and provide a successful working model for treatment fidelity implementation in a large, multi-site behavioral intervention study. In this paper we summarize 20 specific treatment fidelity strategies used in the SMART trial and how these strategies correspond with NIH BCC recommendations in 5 specific areas: 1) study design, 2) training providers, 3) delivery of treatment, 4) receipt of treatment, and 5) enactment of treatment skills. Increased use and reporting of treatment fidelity procedures is essential in advancing the reliability and validity of behavioral intervention research. The SMART trial provides a strong model for the application of fidelity strategies to improve scientific findings and addresses the absence of published literature illustrating the application of BCC recommendations in behavioral intervention studies.