DR11 DataRelease
Release Date: 08/01/2014
| SDY281: Study responses of Adult and neonatal APCs to TLR ligands | |||||||
| Status: | New | ||||||
| Description: | The assays in this study entail stimulation of adult and neonatal blood cells with various concentrations of defined prototype ligands for TLRs 1-9. Multiparameter flow cytometry was used to detect intracellular cytokines (TNF, IL-6, IL-10, IL-12p40, IL-12p70, and IFN-alpha) in whole blood and PBMCs. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M38S6PGG9Z | ||||||
| Subjects: | 80 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY282: Gene expression changes in neonatal and adult plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) upon TLR7/8 stimulation | |||||||
| Status: | New | ||||||
| Description: | Differences in gene expression changes between neonatal and adult plasmacytoid dendritic cells upon stimulation with TLR7/8 may point to specific signaling pathways which, in turn, may account for the known differential immune response of babies to vaccination or infection when compared to adults. Total RNA obtained from MACS-purified human pDC and mDC (using Miltenyi's Dendritic Cell Isolation Kits) that had been stimulated with the synthetic TLR7/8 ligand 3M-003 (at final concentration of 5 uM) for 1 or 6 hours in vitro compared to unstimulated pDC. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M36NXB3CP1 | ||||||
| Subjects: | 24 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY283: Exploration of molecular mechanism(s) for TLR ligand response differences between adults and neonates | |||||||
| Status: | New | ||||||
| Description: | The study performed expression microarrays on RNA from purified subsets of neonatal and adult APCs, which were stimulated or not stimulated with a TLR ligands of interest. Arrays were performed on cells from neonatal and adult individuals, and the arrays for all will be run in parallel on the same day. This study used ELISA to assess the abundance and activation induced modifications of relevant TLRs, adaptors and downstream signaling pathway components. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M30USX09NF | ||||||
| Subjects: | 89 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY284: Human TLR4/MD-2 knockin (KI) mice and comparison of TLR4 agonists ability to enhance innate immunity and development of adaptive immunity in mice | |||||||
| Status: | New | ||||||
| Description: | The study's aim is to generate knockin (KI) mice expressing human TLR4 (huTLR4KI mice), human MD-2 (huMD-2KI mice) and both human TLR4 and MD-2 (TLR4/MD-2 KI mice) rather than the endogenous murine gene(s). The rationale is that differences in responses to non-enteric (variant) LPSs between humans and mice may limit the applicability of murine models as a means to 1) assess host responses to infection with organisms like Y. pestis, from which LPS triggers little response via human compared to murine TLR4/MD-2. 2) evaluate the safety and efficacy of purified/synthetic TLR4 ligand immunotherapeutics. Initial characterization of KI mice was done to determination the safety of MPL, a purified TLR4 agonist, in TLR4/MD-2 KI mice compared to wildtype mice. The study generated data to evaluate the ability of MPL (and for comparison a CpG TLR9 agonist) to enhance antibody and T cell responses and thus protective immunity induced by immunization of wildtype and TLR4/MD-2 KI mice with F1 plus V antigen from Y. pestis. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M30ZC7U5IW | ||||||
| Subjects: | 5 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY302: IL-21 expression during H. pylori infection | |||||||||||
| Status: | New | ||||||||||
| Description: | The development of gastritis during Helicobacter pylori infection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa during H. pylori infection, we combined mathematical modeling of CD4(+) T cell differentiation with in vivo mechanistic studies. We infected IL-21-deficient and wild-type mice with H. pylori strain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. Chronically H. pylori-infected IL-21-deficient mice had higher H. pylori colonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. These in vivo data were used to calibrate an H. pylori infection-dependent, CD4(+) T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-g) and IL-17 during chronic H. pylori infection. The model predicted activated expression of T-bet and ROR?t and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4(+) splenocyte-specific tbx21 and rorc expression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4(+) T cell-specific IL-10 expression in H. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronic H. pylori infection in a STAT1- and STAT3-dependent manner, therefore playing a major role controlling H. pylori infection and gastritis. Importance: Helicobacter pylori is the dominant member of the gastric microbiota in more than 50% of the world's population. H. pylori colonization has been implicated in gastritis and gastric cancer, as infection with H. pylori is the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis during H. pylori infection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized with H. pylori as an alternative to aggressive antibiotics. | ||||||||||
| Program/Contract: |
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| DOI: | 10.21430/M3HIA408ZR | ||||||||||
| Subjects: | 36 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY352: Omega-3 Fatty Acids That Affect the Immune System in Kidney Transplant Patients | |||||||
| Status: | New | ||||||
| Description: | Short-term survival rates of donor tissue after kidney transplantation have improved significantly in recent years because of improved immunosuppression. Rates of long-term tissue loss have changed less because of a high incidence of chronic rejection, infectious complications, and cardiovascular disease. Data suggest that both early and late complications might be reduced in transplant recipients by dietary intervention to raise levels of omega-3 fatty acids and arginine. Prior to transplantation, participants are randomized to one of three groups. Group 1 participants serve as controls and receive no dietary supplements. Participants in Group 2 receive daily nutritional supplements of arginine and canola oil according to body weight. Group 3 participants receive daily nutritional supplements of arginine and a fish oil emulsion according to body weight. All participants receive a standard, low-fat dietary consultation. The status of participants is evaluated peri-transplant and at 1, 3, 6, and 9 months. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3DLCE81CY | ||||||
| Subjects: | 81 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY354: A Study To Test An Anti-Rejection Therapy After Kidney Transplantation | |||||||
| Status: | New | ||||||
| Description: | Renal transplantation is recognized as the treatment of choice for children with chronic renal failure. However, patient and graft survival rates in young children are unacceptably low. In preliminary studies, OKT3 (a monoclonal antibody) induction therapy received post transplant has been more successful than standard immunosuppression alone in improving graft survival. This study is designed to assess the impact of induction therapy on graft survival in pediatric kidney transplant patients. Patients are assigned to OKT3 induction or no induction in a 1:1 ratio. Randomization to oral cyclosporine of either Sandimmune or Neoral is also done in a 1:1 ratio. Group 1 receives OKT3 intraoperatively followed by Neoral. Group 2 receives OKT3 intraoperatively followed by Sandimmune. OKT3 is administered at 2.5 mg (if weight less than 30 kg) or 5 mg (if weight above 30 kg) per day for a maximum of 14 days. Group 3 receives IV cyclosporine followed by Neoral. Group 4 receives IV cyclosporine followed by Sandimmune. Oral cyclosporine is administered in a masked preparation. The dose for Sandimmune and Neoral is the same; patients 6 years of age and older begin at a dose of 15 mg/kg/day and patients under 6 years of age receive 500 mg/m2/day. Patients will receive concomitant medications including steroids (IV and po), Nifedipine, anti-CMV therapy, Bactrim, Azathioprine or Mycophenolate Mofetil. Kidney function, incidence of viral infection, graft survival, and incidence of malignancy will be measured to assess the role of OKT3 induction and the role of rejection in graft failure. Graft function will be evaluated at 1-, 2-, and 4-year intervals. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3APBCA91H | ||||||
| Subjects: | 292 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY355: An Evaluation of IV Gamma Globulin As a Method to Improve Kidney Transplant Survival in Patients With End-Stage Renal Disease Who Are Highly Sensitized to Transplant Antigens | |||||||
| Status: | New | ||||||
| Description: | Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). However, many patients do not receive this treatment due to immune sensitization to HLA antigens. IVIG has been shown to somewhat reduce anti-HLA antibody activity. By blocking this activity, IVIG may make transplants more feasible and increase graft survival in transplant recipients. Patients are randomized to receive IV infusion of either 2 g/kg (maximum dose 180 g) IVIG 10% S/D (Gamimune-N, 10%, manufactured by Bayer) or placebo (0.1% human albumin, manufactured by Bayer) at time of dialysis at study entry and monthly for 3 months. If patients have not received a transplant at 1 year, they receive a booster dose of IVIG or placebo; patients receive another booster at 24 months if transplant still has not occurred. If transplant occurs, patients receive 2 g/kg (up to 180 g) IVIG or placebo monthly for 4 months, beginning at time of transplant. Before and after initiation of IVIG/albumin placebo treatment, specific immune parameters, including panel reactive antibodies (PRA) levels, MLR, serum inhibition of MLR, and cytokine gene transcription in the MLR, and AECA levels are measured. Outcomes studied include time on dialysis and graft survival rates. | ||||||
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| DOI: | 10.21430/M30FFHBV3W | ||||||
| Subjects: | 26 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY356: IG03 Improving Transplant Options of Highly Sensitized Recipients Using IGIV-C 10% | |||||||
| Status: | New | ||||||
| Description: | Kidney transplantation has emerged as the treatment of choice for patients with end-stage renal disease (ESRD). Preliminary data suggest that IGIV therapy could have significant benefits in modifying allograft rejection episodes, stabilizing long-term allograft function, and reducing ischemia/reperfusion injury. Qualified patients will have an in-vitro assessment of the ability of IGIV-C, 10% to convert the donor-specific crossmatch (cytotoxic assay) from positive to negative. Those patients with successful in-vitro conversion of the donor-specific crossmatch assay will be randomized to receive IGIV-C, 10% intravenously at a dose of either 2 gm/kg, 1 gm/kg, or 0.5 gm/kg. IGIV-C, 10% will be administered 3 to 5 days prior to planned transplantation and, if transplantation is successful, 7 days post-transplant. If after receiving the IGIV-C infusion the donor-specific crossmatch reveals that cell death has fallen to 20% or less above background, the crossmatch will be considered negative. If after receiving one infusion the crossmatch remains positive, additional IGIV-C infusions may be administered at one-month intervals, up to 4 infusions. A repeat crossmatch must be obtained after each infusion. Patients will be followed for 12 months post-transplant. Concomitant therapy will include a standard immunosuppression regimen of mycophenolate mofetil, tacrolimus, and prednisone following induction therapy with thymoglobulin. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3TH57S6X3 | ||||||
| Subjects: | 74 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY357: VZV A Study of the Safety and Effectiveness of Varivax (the Chicken Pox Vaccine) in Children Who Have Received Kidney Transplants | |||||||
| Status: | New | ||||||
| Description: | Pediatric renal transplant patients face a lifetime of immunosuppressive therapy that places them at high risk for potentially life-threatening infection by primary varicella-zoster virus (VZV). Treatment for acute episodes of VZV infection is possible but expensive and provides no long-term protection from VZV. Furthermore, therapy to overcome VZV infections can lead to renal graft rejection. Varivax has proven safe, immunogenic, and effective in the normal host and has been recommended for universal administration in the general population at age 12 months. It is not currently labeled for use in immunocompromised patients. However, recent studies in pediatric leukemia and pediatric renal transplant patients suggest that attenuated live vaccine can confer protection with minimal adverse events even in the presence of immunosuppression, providing encouragement for more careful studies of VZV immunization in renal transplant patients. This study endeavors to quantify the immunogenicity and safety of Varivax in the population of pediatric renal transplant patients least susceptible to VZV infection, i.e., those on minimal maintenance immunosuppression and at least 1 year from transplant. Patient enrollment is staged to allow study physicians to closely monitor patients for signs of disseminated varicella reactions or graft rejection. Initially only 1 patient will be enrolled in the study. If the first patient reaches Week 8 without a severe adverse reaction, 3 study centers will then enroll 3 additional patients. If 8 weeks later these 3 patients have had no severe adverse reactions, the same 3 study centers will enroll 3 more patients. At the end of this period, having ascertained the safety of the vaccine in the first 7 patients, the study will be opened to the remaining centers. Patients receive 2 doses of Varivax 6 to 8 weeks apart. Each week for 6 to 8 weeks after the first vaccine dose, the patient undergoes venipuncture and clinical assessment to characterize renal graft and liver function and identify any signs of varicella infection. Additional telephone follow-up occurs on Day 4 and twice weekly thereafter. Parents or guardians monitor the patient for evidence of rash or fever and immediately report any rashes or fevers to study physicians. If, after 6 to 8 weeks, the patient demonstrates no severe reactions to the vaccine and requires no antiviral therapy, the patient receives the second vaccine dose. The patient again receives weekly on-site and telephone follow-up for 6 weeks. Other visits occur 9 weeks and 14 weeks after the second vaccine dose and 1 year after the first vaccine dose. At these visits the patient undergoes venipuncture and clinical assessment to identify potential rejection events or varicella infection and to characterize VZV antibody responses and cytokine changes in response to the vaccine. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3ZY0O1Z91 | ||||||
| Subjects: | 7 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY358: SRL1 A Study to Compare Treatment With Sirolimus Versus Standard Treatment in Patients Who Have Received a Kidney Transplant | |||||||
| Status: | New | ||||||
| Description: | Successful kidney transplantation has gradually improved over the years; much of the improvement has resulted from the use of CsA. However, adequate and tolerable immunosuppression is difficult to achieve with CsA, and rejection episodes are still frequent. CsA is nephrotoxic, with drug toxicity often masking rejection episodes. Other immunosuppressant therapies can result in a range of complications, including metabolic disturbances, adrenocortical insufficiency, and increased risk for infections. Therefore, more effective drugs with less toxicity are needed to prevent acute rejection, especially in the pediatric population where the overall graft survival rate remains significantly lower when compared with that of adult transplant recipients. SRL is an immunosuppressive agent being developed for the prophylaxis of acute renal allograft rejection. SRL has a unique mechanism of action. It inhibits T and B cell activity. In Phase I and II trials in adults, SRL was generally well tolerated and exhibited no apparent nephrotoxic properties, and significantly lower rates of rejection were seen with SRL when compared to placebo. Patients receive extensive prestudy screening, which includes a renal core biopsy, chest x-ray, bone density study, blood tests, and glomerular filtration rate (GFR). Patients are then randomly assigned to 1 of 2 study treatment groups in a 2:1 ratio (142 patients receive SRL, CsA/tacrolimus, and corticosteroids and 71 patients receive standard CsA or tacrolimus-based double or triple drug therapy). SRL is administered as an oral dose of 3 mg/m2/day. Patients are followed for 3 years on therapy, and then for 1 month of follow-up. A renal core biopsy is performed at the time of study entry and at Months 6, 18, and at early termination of patient in study. Patients undergo physical examinations and various blood tests at specified time intervals during the 37-month study period. Efficacy is assessed by comparing the composite endpoint of biopsy-proven acute rejection, graft loss, or death after 36 months of treatment. Safety is assessed by comparing the composite endpoint of graft loss or death after 36 months of treatment. | ||||||
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| DOI: | 10.21430/M3XM74FAOK | ||||||
| Subjects: | 102 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY162: Immunologic and genomic signatures of response to Hepatitis C Virus infection. | |||||||
| Status: | Updated | ||||||
| Description: | Examine the immune response in primary immune cells from subjects who have spontaneously cleared HCV compared to HCV chronically infected subjects | ||||||
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| DOI: | 10.21430/M3TI5NZ7VL | ||||||
| Subjects: | 20 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY167: VRC304 - A Phase I Study of the Safety and Immunogenicity of a Recombinant DNA Plasmid Vaccine (VRC-AVIDNA036-00-VP) Encoding for the Influenza Virus H5 Hemagglutinin Protein in Healthy Adults | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | The primary objective was to evaluate the safety and tolerability of an investigational vaccine VRC-AVIDNA036-00-VP in humans at doses 1 mg and 4 mg administered intramuscularly using a needle-free injection system. The secondary objectives included evaluation of whether VRC-AVIDNA036-00-VP (at doses 1 mg and 4 mg) induced antibodies as assessed by an HAI assay at Day 0 and Week 12. Exploratory analyses included evaluation of the immunogenicity of VRC-AVIDNA036-00-VP at doses 1 mg and 4 mg using intracellular cytokine staining, ELISpot, neutralizing antibody assay, HAI assay to H1 or H3HA or other immunological assays at time intervals between Day 0 and Week 42. | ||||||||||||
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| DOI: | 10.21430/M3SGHW16WZ | ||||||||||||
| Subjects: | 45 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||
| SDY212: Apoptosis and other immune biomarkers predict influenza vaccine (TIV 2008) responsiveness | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to indentify benchmarks of immunological health, influenza vaccination was used in 30 young (20-30 years) and 59 older subjects (60 to 89 years) as models for strong and weak immune responses, respectively. Serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation were measured. Using machine learning, nine variables predicting antibody response with 84% accuracy were identified. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. | ||||||||||||
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| DOI: | 10.21430/M37NGTHMDS | ||||||||||||
| Subjects: | 91 | ||||||||||||
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| Clinical Assessments: | None | ||||||||||||